National Academies Press: OpenBook

Assessing Medical Technologies (1985)

Chapter: Appendix A: Profiles of 20 Technology Assessment Programs

« Previous: 7. Conclusions and Recommendations
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 255
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 256
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 257
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 258
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 259
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 260
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 261
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 262
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 263
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 264
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 265
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 266
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 267
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 268
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 269
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 270
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 271
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 272
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 273
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 274
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 275
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 276
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 277
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 278
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 279
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 280
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 281
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 282
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 283
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 284
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 285
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 286
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 287
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 288
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 289
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 290
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 291
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 292
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 293
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 294
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 295
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 296
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 297
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 298
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 299
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 300
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 301
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 302
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 303
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 304
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 305
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 306
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 307
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 308
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 309
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 310
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 311
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 312
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 313
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 314
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 315
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 316
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 317
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 318
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 319
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 320
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 321
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 322
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 323
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 324
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 325
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 326
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 327
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 328
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 329
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 330
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 331
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 332
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 333
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 334
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 335
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 336
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 337
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 338
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 339
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 340
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 341
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 342
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 343
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 344
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 345
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 346
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 347
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 348
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 349
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 350
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 351
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 352
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 353
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 354
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 355
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 356
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 357
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 358
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 359
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 360
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 361
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 362
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 363
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 364
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 365
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 366
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 367
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 368
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 369
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 370
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 371
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 372
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 373
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 374
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 375
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 376
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 377
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 378
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 379
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 380
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 381
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 382
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 383
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 384
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 385
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 386
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 387
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 388
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 389
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 390
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 391
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 392
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 393
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 394
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 395
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 396
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 397
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 398
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 399
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 400
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 401
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 402
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 403
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 404
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 405
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 406
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 407
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 408
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 409
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 410
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 411
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 412
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 413
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 414
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 415
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 416
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 417
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 418
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 419
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 420
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 421
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 422
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 423
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 424
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 425
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 426
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 427
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 428
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 429
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 430
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 431
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 432
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 433
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 434
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 435
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 436
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 437
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 438
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 439
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 440
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 441
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 442
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 443
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 444
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 445
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 446
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 447
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 448
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 449
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 450
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 451
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 452
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 453
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 454
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 455
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 456
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 457
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 458
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 459
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 460
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 461
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 462
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 463
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 464
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 465
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 466
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 467
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 468
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 469
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 470
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 471
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 472
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 473
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 474
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 475
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 476
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 477
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 478
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 479
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 480
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 481
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 482
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 483
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 484
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 485
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 486
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 487
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 488
Suggested Citation:"Appendix A: Profiles of 20 Technology Assessment Programs." Institute of Medicine. 1985. Assessing Medical Technologies. Washington, DC: The National Academies Press. doi: 10.17226/607.
×
Page 489

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

APPENDIX A Profiles of 20 Technology Assessment Programs Clifford S. Goodman* The profiles of 20 medical technology as- sessment programs in the United States con- tained in this appendix illustrate the great variety in a common framework—of assess- ment activities in major sectors of the Ameri- can health care system. The profiles repre- sent selected assessment activities of medical societies, medical product makers, govern- ment assessment organizations, health care provider organizations, third-party payers, universities, and independent evaluators and policy research organizations. The informa- tion assembled for these profiles provided much of the basis for preparing Chapter 2, "The Scope of Medical Technology Assess- ment." The 20 profiled programs are the fol- lowing: Joint American College of Cardiology/Amer- ican Heart Association Task Force on As- sessment of Cardiovascular Procedures American College of Physicians Clinical Effi- cacy Assessment Project American Hospital Association Hospital Technology Series Program American Medical Association Diagnostic * National Research Council Fellow, National Academy of Sciences, Washington, D.C. 255 and Therapeutic Technology Assessment Program Battelle Memorial Institute Human Affairs Research Centers Blue Cross and Blue Shield Association Medi- cal Necessity Program Blue Cross and Blue Shield Association Tech- nology Evaluation and Coverage Program ECRI Institute of Society, Ethics and the Life Sci- ences (Hastings Center) The Permanente Medical Group, Inc., Divi- sion of Health Services Research Medtronic Inc. National Center for Health Services Research and Health Care Technology Assessment Office of Health Technology Assessment National Heart, Lung, and Blood Institute National Institutes of Health Office of Medi- cal Applications of Research Consensus Development Program National Library of Medicine Congressional Office of Technology Assess- ment Health Program Prospective Payment Assessment Commis- s~on Smith Kline & French Laboratories Cost- Benefit Studies Program University of California at San Francisco In- stitute for Health Policy Studies

256 Veterans Administration Cooperative Stud- ies Program The profiles were prepared by assembling information from personnel of the profiled programs, program publications, reports in the literature, and other sources. in each case, at least two drafts were provided to pro- gram personnel to be reviewed for matters of fact, for updating since previous drafts, and for generating suggestions for content. The profiles could not have been written without the gracious assistance of the individuals shown at the end of this introductory section; however, any errors or inadequate represen- tations are solely the responsibility of the pre- parer of this appendix. Although the programs are profiled ac- cording to the same 16 information catego- ries, the attempt was made to retain the per- spective and flavor of the individual programs. Profile narratives are arranged as follows. Introduction Purpose Subjects of Assessment Stage of Diffusion Concerns Requests Selection Process Assessors Turnaround Reporting Impact Reassessment Funding/Budget Examples Sources These profiles are a start at systematically characterizing current technology assessment activities in the United States. The nrofile.s are intended to answer the who, what, where, why, how, and how much of technol- ogy assessment of the 20 selected programs. Profiles such as these may be useful for the type of technology assessment clearinghouse recommended in this report. They could be published or made available on-line and up- dated periodically. Organizations already profiled could make additions and modifica- tions annually, or perhaps continuously, as might be the case with an on-line system. Or- ganizations wishing to be included could work with clearinghouse staff to develop a new profile, much in the manner in which these were prepared. The sources of financial support for such an ongoing activity could in- ASSESSING MEDICAL TECHNOLOGY elude publication fees, subscriptions, or other types of access fees. The possibilities for valuable cross-cuts of the profile data are many. Distributions of assessment programs such as those shown in Chapter 2 may be helpful in portraying gaps in and other characteristics of overall assess- ment activity. Listings of assessments by spe- cific technologies would be useful for organi- zations contemplating their own assessments of these technologies, or seeking information concerning procurement or use of technolo- gies. Each profile begins with a summary sec- tion portraying the program's major concerns and technologies assessed in matrix form, and checklists summarizing the stage of technolo- gies assessed, application of technologies, as- sessment methods, and approximate annual budget. The summary sections cannot substi- tute for the profile narratives. The summary sections necessarily make categorical distinc- tions where these may not be so clear in prac- tice. The following discussion and definitions may be helpful in understanding the matrix and checklists of assessment activities in the summary sections of each profile. TECHNOLOGY As noted and discussed in Chapter 1, the usage of the terms medical technology and assessment are those of the congressional Of- fice of Technology Assessment. For the pur- poses of the summary sheets, OTA's usage is expanded upon as follows. Drug: any chemical or biological substance that may be applied to, ingested by, or in- jected in order to prevent, treat, or diag- nose disease or other medical conditions. Included are biologicals such as vaccines and blood products, medicinals and botan- icals, and pharmaceutical preparations. Device: any physical item, excluding drugs, used in medical care. Included are diag- nostic and therapeutic equipment, pros- theses, surgical and medical instruments and supplies, dental equipment and sup- plies, ophthalmic goods, and in vitro diag- nostic products reagents, instruments, and systems used in the collection, prepa-

APPENDIX A: PROFILES ration, and examination of specimens taken from the human body to determine the state of a patient's health. Medical or surgical procedure: a practice of a health care provider that generally in- volves a combination, often quite complex, of special skills or abilities with drugs, de- vices, or both. In some cases, the drugs or devices involved are not predominant fac- tors in a procedure. Instead, the technique of the provider performing the procedure is most important, such as in the perfor- mance of a surgical procedure facilitated by the use of scalpels, clamps, and drugs against infection. Psychotherapy or pre- scription of a special diet are examples of procedures which may not involve drugs or devices. Support system: a system that provides the environment for and otherwise facilitates the provision of health care, but is not the focal technology in a medical regimen, sur- gical procedure, or other form of health care. Examples are laboratory and radiol- ogy services, medical information systems, blood banking services, hospital infection control programs, food services, laundry, hospital facilities, and physical plant. Many of these are often referred to as ancil- lary services, and some might be said to comprise the infrastructure of health care delivery. Organizational/administrative system: used in management and administration to en- sure that health care is delivered as effec- tively as possible. Included are alternative delivery modes or settings, e.g., health maintenance organizations (HMOs), area- wide emergency care systems, and home health delivery, and payment systems, e.g., prepayment using diagnosis-related groups. The last two categories support and organi- zational/administrative systems—are often considered to be subjects of health services re- search. This classification of technologies recog- nizes that a given technology may be com- prised of as well as part of other technologies. A drug may be a concoction of multiple chemical entities packaged in a capsule; a 257 medical device may be made of valves, biomaterials, and microchips; a surgical pro- cedure may involve drugs and medical de- vices as well as the surgeon's skilled hand. An area-wide emergency medical care system may encompass all of these, plus ambu- lances, helicopters, communications systems, and more. An organization such as the Pro- spective Payment Assessment Commission may have to evaluate aspects of drugs, de- vices, medical and surgical procedures, and support systems in order to adjust an admin- istrative technology prospective payment using diagnosis-related groups. In portraying the technologies assessed by the programs, Xs are placed across from drugs and medical devices/supplies/equip- ment when program assessments directly ad- dress the properties of the medical products themselves. Where a medical product is not the predominant factor in a procedure, or where the properties of the medical product are taken as given and the emphasis of the as- sessment is on the concerns of a product- embodied procedure relative to another, Xs are placed across from medical/surgical pro- cedure only. For instance, for the purpose of the summary section charts, an ECRI assess- ment of mechanical ventilators to measure and compare various technical properties of several brands of these devices would be con- sidered an equipment assessment. On the other hand, an assessment by a third-party payer of the circumstances under which in- termittent positive-pressure breathing using mechanical ventilators is medically necessary and therefore reimbursable would be shown as an assessment of a medical procedure. The unusual type of assessment, e. g., where a third-party payer primarily assesses medical and surgical procedures but has in an instance assessed ambulance services (a support technology), may not be noted as a major emphasis in the summary section charts. CONCERNS An assessment may address one or more of many concerns, attributes, or properties of a technology. The summary section groups a number of these into four categories.

258 Safety: a judgment of the acceptability of risk in a specified situation' e.g., for a given medical problem, by a provider with speci- fied training, at a specified type of facility. Efficacy: benefit for a given medical problem under ideal conditions of use. Effectiveness: benefit for a given medical problem under average conditions of use. Cost/cost-effectiveness/cost-benefit: includes costs, charges, pricing, cost-benefit, cost- effectiveness, and related concerns. Specif- ically: Cost-benefit: the costs of a project or technological application compared to the resultant benefits, with both costs and benefits expressed in the same units. This unit is nearly always monetary. Cost-effectiveness: the costs of a project or of alternative projects compared to the resultant benefits, with cost and benefits/effectiveness not expressed by the same unit. Costs are usually ex- pressed in dollars, but benefits/effective- ness are ordinarily expressed in terms such as lives saved, disability avoided, quality-adjusted life years saved, or other relevant objectives. Ethical/legal/social: includes implications of technology for societal norms, morals, in- stitutions, and relationships; and eco- nomic, medical, legal, and cultural values. Effectiveness in the summary section charts refers not only to the absolute benefit of the technology taken alone, but also to the marginal benefits to be gained from use of a technology under particular circumstances, considering a given patient's status and the use of and information gained from other technologies. Thus, appropriateness, a pri- mary concern of several of the profiled pro- grams, is categorized in the summary sections under effectiveness and/or cost-effectiveness, where cost is an explicit consideration in determining appropriateness. Evaluations of the sensitivity, specificity, and other operat- ing characteristics of diagnostic technologies are efficacy/effectiveness concerns. Again, the summary section matrices cite the major program emphases. Thus, al- though many of the profiled programs have legal departments or various legal require- ASSESSING MEDICAL TECHNOLOGY meets in connection with their assessment ac- tivities, Xs are placed under the ethical/legal/ social concerns column only for those programs having these as central concerns of their assessments. STAGE OF TECHNOLOGIES ASSESSED Emerging: in the applied research stage, about the time of initial clinical testing, e.g., monoclonal antibodies for immuno- therapy of cancer. New: past the stage of clinical trials but not yet in widespread use, e.g., extracorporeal lithotripsy for treatment of kidney stones. Established: considered by providers to be a standard approach to a particular condi- tion and diffused into general use. Obsolete/outmoded: superseded by another technology and/or demonstrated to be in- effective or harmful, e.g., gastric freezing for peptic ulcer. Technologies may be assessed at different stages of diffusion. The point in a technolo- gy's life cycle at which it is assessed may de- pend upon the purposes of an assessment pro- gram, and the course of the life cycle may be affected by the assessment itself. For new drugs and certain devices, FDA regulatory requirements may mediate technological dif- fusion before, during, and after assessment benchmarks such as initiation of clinical tri- als, approval for marketing, and removal from the market in the case of a product found to pose an imminent health hazard. Indeed, as discussed in Chapter 2, technolo- gies may be assessed for the very purpose of determining their stage of diffusion. APPLICATION OF TECHNOLOGIES Prevention: protects an individual from dis- ease, e.g., vaccination. Diagnosis: helps in determining what disease processes occur in a patient, e.g., upper gastrointestinal endoscopy. Screening: detects disease or abnormality, or potential for these, often in asymptomatic patients, e.g., Pap smear for cervical can- cer.

APPENDIX A: PROFILES Treatment: relieves an individual from dis- ease and its effects, including technologies that cure disease and those that give symp- tomatic relief but do not alter the underly- ing disease process, e.g., drug therapy for depression. Rehabilitation: to restore to a condition of health or useful and constructive activity, e. g., assistive devices for severe speech im- pairment. ASSESSMENT METHODS Laboratory testing: nonclinical (in vitro) testing of medical technology, e.g., for drug, device, or equipment performance. Clinical trials: prospective clinical experi- ments designed to test the safety and effi- cacy of a medical technology in which peo- ple are assigned to experimental or control groups and outcomes are compared. In- cludes randomized controlled clinical tri- als, in which people are randomly assigned to experimental and control groups. Epidemiological and other observational methods: excludes the more rigorous ex- perimental design studies such as random- ized clinical trials. Included are such stud- ies known as quasiexperiments; series; case studies; cohort studies; natural experi- ments; and certain cross-sectional, case control, and longitudinal methods. Cost analyses: analyses, including cost-bene- fit and cost-effectiveness analyses, that enumerate, measure, and compare both the benefits and costs of medical technolo- gies. Analyses may vary in terms of per- spective (i.e., the parties to whom the ben- efits and costs accrue) and the choice and valuation of the benefits and costs consid- ered. Simulation/modeling: use of models repre- sentations of real-world phenomena to test or evaluate proposed interventions, of- ten undertaken when evaluation of the ac- tual intervention would be impractical. Simulations may involve manipulation of iconic, analog, or symbolic (often mathe- matical) models. Group judgment: a process in which a group of experts interact in assessing a technology 259 and formulate findings by vote or other process of reaching general agreement. The findings may note minority opinions; the group may determine that there is no consensus of opinion. The process may be informal, or it may be a formal one such as the nominal group or Delphi technique. Members of the group may be involved in drafting, editing, reviewing, and/or com- menting upon the findings. To be catego- rized as a group judgment it is necessary that group members have the opportunity to interact in formulating and reviewing each other's and the group's observations and findings. Expert opinion: consultation with individual experts who may be involved in drafting, editing, reviewing, or commenting upon assessments, but who do not interact as a group. Literature syntheses: summarizing, integrat- ing, and interpreting research findings re- ported in the literature. May include un- structured literature reviews as well as various systematic and quantitative proce- dures such as meta-analysis. ACKNOWLEDGMENTS I wish to thank the following individuals for providing source material, reviewing drafts of the profiles, and sharing important insights into the assessment programs of which they are a part. John R. Ball, American College of Physicians Clyde I. Behney, Congressional Office of Tech- nology Assessment Nancy E. Cahill, American Medical Associa- tion Arthur L. Caplan, Hastings Center Enrique D. Carter, National Center for Health Services Research Susan M. Clark, National Institutes of Health Office of Medical Applications of Research Morris F. Collen, Kaiser Permanente Medical Care Program Dennis I. Cotter, Prospective Payment Assess- ment Commission Martin Erlichman, locational Center for Health Services Research

260 David I. Feild, American College of Cardiol- ogy Robert C. Flink, Medtronic Peter L. Frommer, National Heart, Lung, and Blood Institute Susan Gleeson, Blue Cross and Blue Shield As- sociation Mark D. Goodhart, American Hospital Associ- ation Jerome G. Green, National Heart, Lung, and Blood Institute Ping Huang, Veterans Administration Itzhak Jacoby, National Institutes of Health Office of Medical Applications of Research Richard J. Jones, American Medical Associa- tion Bryan R. Luce, Battelle Memorial Institute Harold Margulies, National Center for Health Services Research Judith D. Moore, Prospective Payment Assess- ment Commission ASSESSING MEDICAL TECHNOLOGY Lawrence C. Morris, Jr., Blue Cross and Blue Shield Association Robert Mosenkis, ECRI jay Moskowitz, National Heart, Lung, and Blood Institute Joel I. Nobel, ECRI Thomas D. Overcast, Battelle Human Affairs Research Centers Morton L. Paterson, Smith Kline & French Laboratories Jonathan A. Showstack, University of Califor- . ~ ~ . nova, ban r ranc~sco Elliot Siegel, National Library of Medicine Kent A. Smith, National Library of Medicine David Tennenbaum, Blue Cross and Blue Shield Association Malin VanAntwerp, ECRI Linda Johnson White, American College of Physicians Donald A. Young, Prospective Payment Assess- ment Commission

loins American College of Carcliology/American Heart Association Task Force on Assessment of Carcliovascular Procedures Heart House, 9111 Old Georgetown Road Bethesda, MD 20814 (301) 897 5400 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety . Efficacy/ Cost/ Cost-Effect/ Effectiveness Cost-Benefit i _ X Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded Application of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $12,000* * This is a rough estimate of the joint ACC/AHA task force budget only, and does not include budgets for other ACC or AHA activities. JOINT AMERICAN COLLEGE OF CARDIOLOGY/AMERICAN HEART ASSOCIATION TASK FORCE ON ASSESSMENT OF CARDIOVASCULAR PROCEDURES Introduction The Joint American College of Cardiol- ogy/American Heart Association Task Force on Assessment of Cardiovascular Procedures is a cooperative assessment effort of the two parent organizations, each of which conducts activities related to cardiovascular health. The American Heart Association (AMA) is a voluntary health agency devoted to the re- 26 auction of premature death and disability caused by heart and blood vessel diseases. The association has 55 affiliates nationwide, and its headquarters are in Dallas. In 1984, AHA provided $43.7 million for biomedical research, $24.6 million for public health edu- cation, $14.8 million for professional educa- tion and training, and $22.6 million for com- . . munlty services. The American College of Cardiology (ACC) is a 13,500-member, nonprofit profes- sional medical society. The mission of the col- lege is to ensure optimal care for persons with cardiovascular disease or the potential for de- veloping it and, ultimately, through appro-

262 priate educational and socioeconomic activi- ties, to contribute to the prevention of cardiovascular disease. Members are physi- cians and scientists concerned with clinical and basic science disciplines related to the cardiovascular system. Among its major activities, the ACC con- ducts a comprehensive program of continu- ing education and establishes standards of cardiovascular care. The college has three mechanisms for the assessment of new medi- cal knowledge and technology. Two of these, the Cardiovascular Procedures Committee and the Cardiovascular Norms Committee, are described briefly in this introductory sec- tion, along with other ACC activities related to assessment. The third, the Joint ACC/ AHA Task Force on Assessment of Cardiovas- cular Procedures, is the main subject of this profile. The ACC Cardiovascular Procedures Committee reviews requests from federal agencies as well as from the private sector (hospitals, clinics, third-party carriers) rela- tive to standards, criteria, appropriateness, etc., of procedures normally performed in a hospital setting by physicians treating cardio- vascular disease. Recommendations are for- warded from this committee to the president of the college. This committee consists of 12 members of the ACC. The ACC Cardiovascular Norms Commit- tee is a new activity begun in 1983. This com- mittee reviews and assists the Executive Committee of ACC and the president in re- sponding to requests concerning standards of care and in assessing proposed standards or norms of particular interest to the college membership. In addition, this committee ob- tains consensus on dynamic norms defined by ACC as factors essential for quality care- for the diagnosis and management of the most common cardiac disorders, including considerations of the cost-effectiveness of al- ternative management plans or diagnostic techniques. This committee consists of eight members of the ACC. Through these committees and related ac- tivities, the ACC has developed positions on such technologies as applicability of and indi- cations for phonocardiography, cardioky- mography, ergonovine testing, percutaneous ASSESSING MEDICAL TECHNOLOGY transluminal coronary angioplasty, pro- grammable pacemakers, transtelephonic pacemaker monitoring, and the training re- quirements for the safe handling of radioiso- topes utilized for cardiovascular diagnostic testing. Opinions have been rendered on au- tomated blood pressure monitoring, heparin infusion pumps, diagnostic endocardial elec- trical stimulation, intraoperative ventricular mapping, Doppler ultrasound, hyperbaric oxygen therapy, photoplethysmography, dig- ital subtraction angiography, and rapid se- quence pyelograms. The ACC has initiated conferences to iden- tify the state of the art on the relative sensitiv- ity, specificity, and indications for diverse techniques in the assessment of ventricular functions. For instance, The Twelfth Be- thesda Conference, held in 1981, on noninva- sive technology in the assessment of ventricu- lar function was a state-of-the-art conference to develop diagnostic strategies for using var- ious types of echocardiography, nuclear car- diologic techniques, cardiac computed to- mography, and digital subtraction angiog- raphy. ACC has testified in support of the Na- tional Heart, Lung, and Blood Institute ap- propriations and authorizations and has sup- ported increased warnings on cigarette packages, the desirability of sodium content labeling for prepared foods, special consid- eration for orphan drugs, and extension of patent protection time for drugs requiring prolonged clinical testing periods. ACC par- ticipates in the Medical Necessity Program of the Blue Cross and Blue Shield Association. The Joint ACC/AHA Task Force on Assess- ment of Cardiovascular Procedures (joint task force) first met in November 1981. Purpose The purpose of the Joint ACC/AHA Task Force on Assessment of Cardiovascular Pro- cedures (joint task force) is to define the role of noninvasive and invasive procedures in the diagnosis and management of cardiovascular disease. As opposed to the ACC Cardiovascu- lar Procedures and Cardiovascular Norms Committees, which respond to inquiries

APPENDIX A: PROFILES made by outside parties the joint task force ... . ' Process initiates its own assessments. Subjects of Assessment The first assessment to be completed was of cardiac pacemaker implantation, in 1984. Assessments ongoing in 1985 were of exercise stress testing and nuclear imaging proce- dures. Among other procedures that are un- der consideration for assessment topics are angiography, Hotter monitoring, echocar- diography, and intracardiac electrophysio- logical studies for management of arrhyth- mias. Stage of Diffusion The program is primarily concerned with new and emerging technologies. Concerns The joint task force is most concerned with the safety and efficacy of cardiovascular pro- cedures. Specifically, it may address the con- tribution, uniqueness, sensitivity, specificity, indications, and contraindications of cardio- vascular procedures. Although the charge of the joint task force also includes cost-effec- tiveness as a potential concern, this has not yet been explicitly addressed in deliberations to date. Requests It is anticipated that the joint task force will develop most of its assessment topics, al- though suggestions may come from either the ACC or the AHA, for instance from the ACC Cardiovascular Procedures Committee via the president. The topic of the cardiac pace- maker implantation was generated by the ACC president, and the topics of exercise stress testing and nuclear imaging were gen- erated by the joint task force. Selection The topics for assessment are chosen by consensus of joint task force members. 263 Assessment reports are written by ad hoc subcommittees designated by the joint task force, e.g., the Subcommittee on Pacemaker Implantation. Portions of the reports are drafted first by individual subcommittee members. In addition to sharing the initial drafts with other subcommittee members, the subcommittee members may also seek ad- vice and information from other experts. Subcommittee members then consolidate their section drafts into a single document, which is reviewed by all subcommittee mem- bers and which may be shared with other ex- perts for their opinion. In the case of the car- diac pacemaker implantation report, the subcommittee met four times. The final subcommittee draft is then for- warded to the joint task force for approval. The joint task force meets at least twice a year; its small size enables much of its work to be conducted by telephone and through the mail. Once approved by the joint task force, reports are forwarded to the presidents of ACC and AHA for approval by the organi- zations' respective ruling bodies. Final ap- proval is given in a letter signed jointly by the presidents of the two organizations. This ap- proval makes the report an official, jointly supported policy statement of the two orga- nizations. Assessors The joint task force has a chairman and four other members, two representing ACC and two representing AHA and designated by their respective organizations. The chair- person of the joint task force is selected by agreement of the two organizations. A1- though it may not always be the case, the chairperson is likely to be a member of one or both organizations. No terms of office have been set for joint task force members. The joint task force selects the subcommittee chairpersons and other subcommittee mem- bers. loins task force members may serve on the subcommittees. Subcommittee members are not necessarily members of either organi- zation and are not necessarily physicians, al-

264 though all subcommittee members appointed to date have been members of both the ACC and the AHA. Thus far, the number of mem- bers on the subcommittees has ranged from 6 to 11. Upon completion of their tasks, the ad hoc subcommittees are dissolved. Turnaround Turnaround time for joint task force re- ports will be variable, depending on the mag- nitude and complexity of the subject. It is anticipated that for most reports full turn- around time will be approximately 18 months. The time from adoption of cardiac pacemaker implantation as an assessment topic to publication of the report was 21 months. This included a year for appoint- ment and work of the subcommittee and ap- proval by the joint task force, 6 months for final approval by the two organizations, and publication 3 months thereafter. Reporting By agreement of ACC and AHA, final as- sessment reports are published simultane- ously in the Journal of the American College of Cardiology and Circulation, which is pub- lished by the AHA. There are 20,000 world- wide individual and organizational sub- scribers to the Journal of the American College of Cardiology, including all ACC members. Circulation goes out to 13,000 U.S. and 10,000 overseas subscribers. The re- ports are also distributed to the other domes- tic and overseas journals and members of the press, policymakers, and other parties that ASSESSING MEDICAL TECHNOLOGY may be interested in a given topic. Copies are also available on request from the ACC and the AHA. Impact There are currently no plans to study the impact of the assessment reports, other than through noting individual reactions to the re- ports and requests for reprints. Reassessment The joint task force will reassess a technol- ogy as warranted by new evidence regarding safety, efficacy, and appropriate use. Funding/Budget Expenses of the joint task force and staffing are shared equally by the two organizations. The annual budget of the joint task force is approximately $10,000 to $15,000. This amount covers direct costs only, and does not include estimates of indirect costs, the cost of staff time, the value of time provided by the committee members, or publication costs. Example On the following pages is the full text of the 1984 report of the Joint ACC/AHA Task Force on Assessment of Cardiovascular Pro- cedures on guidelines for permanent cardiac pacemaker implantation, published in the Journal of the American College of Cardiol- ogy. It is reproduced here with permission.

APPENDIX A: PROFILES Sources American College of Cardiology. 1982. Twelfth Bethesda Conference: Noninvasive technology in the assessment of ventricular function. American Journal of Cardiology 49:1309-1374. American College of Cardiology. 1985. Statements of charge: Joint ACC/AHA Task Force on Assessment of Cardiovascular Procedures (and Subcommittees), Cardiovascular Procedures Committee, and Cardio- vascular Norms Committee. American Heart Association. 1984. American Heart Association 1984 Annual Report. Dallas. Feild, D. J., Director, Special Projects, American College of Cardiology. 1985. Personal communica- tion. Joint American College of Cardiology/American Heart Association Task Force on Assessment of Car- 265 diovascular Procedures (Subcommittee on Pacemaker Implantation). 1984a. Guidelines for permanent car- diac pacemaker implantation, May 1984. Journal of the American College of Cardiology 4~2~: 434-442. Joint American College of Cardiology/American Heart Association Task Force on Assessment of Car- diovascular Procedures (Subcommittee on Pacemaker Implantation). 1984b. Special report: Guidelines for permanent cardiac pacemaker implantation, May 1984. Circulation 70:331A-339A. Knoebel, S. B. 1983a. President's page: The next challenge and balancing individual quality care with community resources. Journal of the American Col- lege of Cardiology 3:972-974. Knoebel, S. B. 1983b. Presentation to the Depart- ment of Health and Human Services Technology Co- ordinating Committee.

266 SPECIAL REPORT ASSESSING MEDICAL TECHNOLOGY Guidelines for Permanent Cardiac Pacemaker Implantation, May 19X4 A report of the Joint American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures (Sub- committee on Pacemaker Implantation). SUBCOMMITTEE MEMBERS ROBERT L. FRYE, MD, FACC, Chairman Rot heater Minnesota JOHN J. COLLINS. MD, FACC Boston. Massachusetts ROMAN W. D~.SANCTIS' MD, FACC B`>sttJn Massuc h~`setts HAROLD T. DODGE, MD. FACC Seattle Washin~,~ton LEONARD S. DREIFUS, MD, FACC Philadelphia Penny! lo ania Background It is becoming more apparent each day that despite a strong national commitment to excellence in health care, the resources and personnel are finite. It is, therefore, ap- propriate that the medical profession examine the impact of developing technology on the practice and cost of medical care. Such analysis, carefully conducted, could potentially impact on the cost of medical care without diminishing the effectiveness of that care. To this end, the American College of Cardiology and the American Heart Association in 1980 established a Joint Task Force on Assessment of Cardiovascular Procedures with the following charge: The Joint Task Force of the American College of Cardiology and the American Heals Association shall define the role of specific noninvasive and invasive procedures in the diagnosis and management of cardiovascular disease. The Task Force shall address, when appropriate, the contribution, uniqueness, sensitivity, specificity, indications and contraindications and cost-effectiveness of such specific procedures. The Task Force shall include a Chairman and four members two representatives from the American Heart Association and two representatives from the American College of Address for reprints: Mr. David J. Feild. Director. Special Projects. American College of Cardiology. 9111 Old Georgetown Road. Bethesda. Maryland 20811. C)1984 by the American College of Cardiology CHARLES FISCH. MD. FACC, Task Force Chairman Indianapolis Indiana LEONARD S. GENRES. MD, FACC Chapel Hill North Carolina PAUL C. GILLETTE. MD. FACC Charleston Soulh Carolina VICTOR PARSONNET. MD, FACC Newark Ned Jerse! T. JOSEPH REEVES, MD, FACC Beaumont Texas SYLVAN LEE WEINBERG, MD. FACC Dayton, Ohio Cardiology. The Task Force may select ad hoc members as needed upon the approval of the Presidents of both . . Organlzatlons. Recommendations of the Task Force are forwarded to the President of each organization. The members of the Joint Task Force are: Roman W. DeSanctis~ MD, Harold T. Dodge, MD, T. Joseph Reeves, MD, Sylvan L. Weinberg, MD and Charles Fisch, MD, Chairman. The Subcommittee on Pacemaker Implantation was chaired by Robert L. Frye, MD and, in addition to the members of the Joint Task Force, included the following ad hoc members: John J. Collins, MD, Leonard S. Dreifus, MD, Leonard S. Gettes, MD, Paul C. Gillette, MD and Victor Parsonnet, MD. This document was reviewed by the officers and other responsible individuals of the two organizations and re- ceived final approval on May 2, 1984. It is being published simultaneously in Circulation and Journal of the American College of Cardiology. The potential impact of this docu- ment on the practice of cardiology and some of its un- avoidable shortcomings are clearly set out in the Introduction. I. Introduction The joint American College of Cardiology/American Heart Association Ad Hoc Task Force on Assessment of Cardio- 0735-1097/84/$3 00 Reprinted with permission from the American College of Cardiology

APPENDIX A: PROFILES vascular Procedures was formed to make recommendations regarding the appropriate utilization of technology in the diagnosis and treatment of patients with cardiovascular dis- ease. One such important technique is that of cardiac pacing. Rapid progress in a number of areas has led to extraordinary and still evolving advances in implantable cardiac pace- makers and in other devices which electrically stimulate the heart. For this reason, and also because of allegations of abuses of this technology, by the medical profession, the Task Force was assigned the task of defining current indi- cations for permanent cardiac pacemakers. These recom- mendations are the subject of this report. Because of the multitude, complexity and initial cost of currently available pacing systems, the Subcommittee has included recom- mendations regarding selection of devices for specific clin- ical problems in which pacing is indicated. The Subcom- mittee recommendations are based on current evidence in relation to both knowledge of the natural history of disorders of cardiac rhythm as well as the characteristics of currently available pacemakers. Because of continuing research and development, some of these recommendations may be sub- ject to modification in even the near future. These recommendations apply to permanent pacing in the management of chronic, though sometimes intermittent, disorders of cardiac rhythm. For the most part they do not pertain to identifiable factors which cause transient depres- sion of cardiac impulse formation and conduction, such as drugs, electrolyte or endocrine imbalances, infection or the acute phase of myocardial infarction. The decision to im- plant a pacemaker must be reached by scrupulous adherence to a fundamental principle of clinical medicine which de- mands a careful, thoughtful analysis of each individual pa- tient by the responsible physician. Attention must be given to the general medical, emotional and mental state of the patient as well as to the specifics of the cardiac rhythm disturbance before a proper decision with respect to pacing can be made. The Subcommittee has not offered any recommendations regarding resources required to perform pacemaker inser- tions, training of individuals for this purpose or the appro- priate follow-up and monitoring of patients with permanent pacemakers. These critically important topics have been addressed elsewhere (1). The Subcommittee unanimously urges careful review of the resource guidelines by all in- stitutional administrators, physicians and surgeons who are responsible for pacemaker therapy. The clinical symptom- atology associated with bradycardia needs definition at the outset since it recurs throughout the report as a major in- dication for permanent pacemaker therapy. In this report, the term ''symptomatic bradycardia'' is used to refer to the following clinical manifestations which are directly attrib- utable to the slow heart rate: transient dizziness, light-head- edness, near syncope or frank syncope as manifestations of transient cerebral ischemia, and more generalized symptoms 267 such as marked exercise intolerance or frank congestive heart failure. Indications for permanent pacemakers have been grouped arc ording to the following c lassific ations: Class I: Conditions for which there is general agreement that permanent pacemakers should be implanted. Class 11: Conditions for which permanent pacemakers are frequently used but there is divergence of opinion with respect to the necessity of their Insertion. Class 111: Conditions for which there is general agree- ment that pacemakers are unnecessary. In those patients being considered for pacemakers, de- cision making may be influenced by the following additional factors: 1) overall physical and mental state of the patient, in- cluding the absence of associated diseases that may result in a limited prognosis for life; 2) presence of associated underlying cardiac disease that may be adversely affected by bradycardia; 3) desire of the patient to operate a motor vehicle; 4) remoteness of medical care, including patients who travel widely or live alone who therefore might be unable to seek medical help if serious symptoms arise; 5) necessity for administering medication that may de- press escape heart rates or aggravate atrioventricular (AV) block; 6) slowing of the basic escape rates; 7) significant cerebrovascular disease that might result in a stroke if cerebral perfusion were to suddenly decrease; and 8) desires of the patient and family. The format of this report consists of a brief definition and description of specific clinical situations in which pacing may be considered, and literature references to document the basis for the recommendations. II. Pacing in Acquired Atrioventricular (AV) Block in Adults Clinically, atrioventricular (AV) block is classified as first degree, second degree or third degree (complete) heart block; anatomically, it is defined as supra-His, intra-His and/or infra-His. Second degree heart block may be further classified as type I (progressive prolongation of PR interval before a blocked beat) or type 11 (no progressive prolon- gation of PR interval before blocked beats). ''Advanced second degree block'' refers to the block of two or more consecutive P waves. Patients with abnormalities of AV conduction may be asymptomatic or they may experience serious symptoms related to profound bradycardia and/or ventricular arrhythmias. Decisions regarding the need for a pacemaker are influenced most importantly by the presence

268 or absence of symptoms that are directly attributable to bradycardia. It is clearly documented that patients with com- plete heart block and syncope have an improved survival with permanent pacing (2-5). There is no evidence to sug- gest that survival is prolonged with pacemakers in patients with isolated first degree AV block. The prognosis in type I second degree AV block, when due to AV nodal delay, tends to be benign (~8). However, in patients with type II second degree AV block (either intra- or infra-His), symp- toms are frequent, prognosis is compromised and progres- sion to complete heart block is common (6,8,9). Recommendations for insertion of permanent pace- makers in patients with AV block with acute myocardial infarction or congenital AV block are discussed in a separate section. AV block in the presence of supraventricular tach- yarrhythmia does not constitute an indication for pacemaker insertion except as specifically defined in the recommen- dations that follow. Indications for Permanent Pacing in Acquired AV Block in Adults Class I. A. Complete heart block, permanent or intermittent, at any anatomic level, associated with any one of the following complications: 1. Symptomatic bradycardia (discussed in the Intro- duction). In patients with these symptoms in the presence of complete heart block, the symptoms must be presumed to be due to the heart block unless proven to be otherwise. 2. Congestive heart failure. 3. Ventricular ectopy and other conditions that re- quire treatment with drugs which suppress the automaticity of escape foci. 4. Documented periods of asystole of 3.0 seconds or longer, or any escape rate of less than 40 beats/ . . . mm In symptom-tree patients. 5. Confusional states which clear with temporary pacing. B. Second degree AV block, permanent or intermittent, regardless of the type or the site of the block, with symptomatic bradycardia. C. Atrial fibrillation, atrial flutter or rare cases of supra- ventricular tachycardia with complete heart block or advanced AV block, bradycardia and any of the con- ditions described under l-A. The bradycardia must be unrelated to digitalis or drugs known to impair AV conduction. Class II. A. Asymptomatic complete heart block, permanent or intermittent, at any anatomic site, with ventricular rates of 40 beats/min or faster. ASSESSING MEDICAL TECHNOLOGY B. Asymptomatic type 11 second degree AV block, per- manent or intermittent. C. Asymptomatic type I second degree AV block at intra-His or infra-His levels. Class III. A. First degree AV block (see section on bi-trifascicular block). B. Asymptomatic type I second degree AV block at the supra-His (AV nodal) level. III. Pacing in Atrioventricular (AV) Block Associated With Myocardial Infarction Indications for permanent pacing after myocardial in- farction in patients experiencing AV block are related in large measure to the presence of intraventricular conduction defects. The requirement for temporary pacing in acute myo- cardial infarction does not by itself constitute an indication for permanent pacing. The long-term prognosis in survivors of acute myocardial infarction who have had AV block is related primarily to the extent of myocardial injury and the character of intraventricular conduction disturbances, rather than to the AV block per se (10-14). Patients with acute myocardial infarction who have intraventricular conduction defects, with the exception of isolated left anterior hemi- block, have an unfavorable short- and long-term prognosis and increased incidence of sudden death (10-12). This un- favorable prognosis is not necessarily due to the develop- ment of high grade AV block, although the incidence of such block is higher in postinfarction patients with abnormal intraventricular conduction (12). Unlike some other indi- cations for permanent pacing, the criteria in patients with myocardial infarction and AV block do not necessarily de- pend on the presence of symptoms. Indications for Permanent Pacing After Myocardial Infarction Class 1. A. Patients with persistent advanced second degree AV block or complete heart block after acute myocardial infarction (12,14). Decision for insertion of pace- maker should be made before discharge in this group of patients. Class 1I. A. Patients with persistent first degree AV block in the presence of bundle branch block not documented pre- viously (13). B. Patients with transient advanced AV block and as- sociated bundle branch block. Class III. A. Patients in whom AV conduction disturbances are transient in the absence of intraventricular conduction defects (12).

APPENDIX A: PROFILES B. Patients with transient AV block in the presence of isolated left anterior hemiblock ( I I ). Patients with acquired left anterior hemiblock in the absence of atrioventricular (AV) block. IV. Pacing in Bifascicular and Trifascicular Block (Chronic) Bifascicular and trifascicular block refer to electrocar- diographic evidence of impaired conduction below the AV node in two or three of the fascicles of the right and left bundles. In patients with such electrocardiographic abnor- malities, there is convincing evidence that advanced heart block with symptoms due to the block is associated with a high mortality and a significant incidence of sudden death (5,15). Syncope is common in patients with bifascicular block. It is usually not recurrent, nor is it associated with an in- creased incidence of sudden death (16-18). It has been suggested that although pacing relieves the transient neu- rologic symptoms, it does not reduce mortaility from sudden death (19). There is convincing evidence, however, that in the presence of complete heart block, either permanent or transient, syncope is associated with an increased incidence of sudden death (5). Thus, being unable to define the cause ~ . . ~ . . . ~ . . Of syncope in the presence of bifascicular or trifascicular block, it appears reasonable to assume that the syncope may be due to transient complete heart block and, thus, in the opinion of some investigators, prophylactic permanent pac- ing is indicated (20,21). Although complete heart block is most often Dreceded . by bifascicular block, the evidence is impressive that the rate of progression of bifascicular block to complete heart block is low. Furthermore, no single clinical or laboratory variable, including bifascicular block, identifies patients at high risk of death from a future bradyarrhythmia due to the bundle branch block (22). Of the many laboratory variables, the PR and HV inter- vals have been singled out as possible predictors of complete heart block and sudden death. Evidence indicates that PR prolongation is common in patients with bifascicular block. However, the prolongation is most often at the level of the AV node. Furthermore, there is no correlation between the PR and HV intervals, nor is there a correlation between the length of the PR interval and progression to complete heart block and incidence of sudden death (93,24,28). Although most patients with chronic or intermittent complete heart block demonstrate prolongation of the HV interval during anterograde conduction, and some investigations ( 26 ~ 27 ) have suggested that asymptomatic patients with bifascicular block and a prolonged HV interval be considered for permanent pacing, the evidence indicates that while the prevalence of prolonged HV is high, the incidence of progression to com- 269 plete heart block is low. HV prolongation accompanies ad- vanced cardiac disease and is associated with an increased mortality; death is not sudden and is due to the underlying heart disease, and not to complete heart block ( 16,19, 23,28,29). The prolonged HV interval is, thus, not an in- dependent marker for sudden death (22). Atrial pacing as a means of identifying patients at in- creased risk of future complete heart block probably is not justified. The chance of induction of distal heart block with pacing is low (16,27,30,31). In fact, pacing often fails to induce distal His block in patients with documented abnor- mal conduction ofthe His-Purkinje system ( 16,26,27,32,33). Furthermore, failure to induce distal block cannot be taken as evidence that the patient will not develop complete heart block. However, if atrial pacing induces infra-His block, ~ . . this may be considered an indication for pacing by some (34). Indications for Permanent Pacing in Bifascicular and Trifascicular Block Class I. A. Bifascicular block with intermittent complete heart block associated with symptomatic bradycardia (as defined. B. Bifascicular block with intermittent type 11 second decree AV block with symptoms attributable to the G heart block. Class II. A. Bifascicular or trifascicular block with intermittent tvne 11 second degree AV block without svmotoms. -a rid --on- - B. Bifascicular or trifascicular block with syncope that is not proven to be due to complete heart block, but other possible causes for syncope are not identifiable. C. Pacing-induced infra-His block. Class III. A. Fascicular blocks without AV block or symptoms. B. Fascicular blocks with first degree AV block without symptoms. --a ---r - - V. Pacing in Sinus Node Dysfunction Sinus node dysfunction (sick sinus syndrome) constitutes a spectrum of cardiac arrhythmias, including sinus brady- cardia, sinus arrest, sincatrial block and paroxysmal supra- ventricular tachycardia alternating with periods of brady- cardia or even asystole. Patients with this condition may be symptomatic from paroxysmal tachycardia, bradycardia or both. Correlation of symptoms with the specific arrhythmias is essential. This may be difficult, however, because of the intermittent nature of the episodes. Sinus bradycardia is accepted as a physiologic finding in trained athletes, in whom awake resting heart rates of 40 to 50 beats/min are not uncommon and minimal heart rates during sleep may

270 be as slow as 30 to 43 beats/min with sinus pauses as long as 1.6 to 2.8 seconds (35-37). This is due to increased vagal tone. Permanent pacing in patients with sinus node dys- function may not necessarily result in an improvement in survival (38,39), but severe symptoms related to bradycar- dia may be relieved (40,41). Indications for Permanent Pat ing in Sinus Node Dysfunction Class I. A. Sinus node dysfunction with documented sympto- matic bradycardia. In some patients, this will occur as a consequence of long-term essential drug therapy of a type and dose for which there is no acceptable alternative. Class II. A. Sinus node dysfunction, occurring spontaneously or as a result of necessary drug therapy, with heart rates below 40 beats/min when a clear association between significant symptoms consistent with bradycardia and the actual presence of bradycardia has not been documented. Class III. A. Sinus node dysfunction in asymptomatic patients, in- cluding those in whom substantial sinus bradycardia (heart rate <40 beats/min), is a consequence of long- term drug treatment. B. Sinus node dysfunction in patients in whom symp- toms suggestive of bradycardia are clearly docu- mented not to be associated with a slow heart rate. VI. Pacing in Hypersensitive Carotid Sinus Syndrome The hypersensitive carotid sinus syndrome is defined as syncope resulting from an extreme reflex response to carotid sinus stimulation! It is an uncommon cause of syncope. There are two components to the reflex: 1 ) Cardioinhibitory. resulting from increased parasympa- thetic tone and manifested by slowing of the sinus rate and/or prolongation of the PR interval and advanced AV block; and 2) Vasodepressor secondary to a reduction in sympathetic activity resulting in hypotension. Before concluding that permanent pacing is clinically indicated, determination of the relative contribution of the two components of carotid sinus stimulation to the individ- ual patient's symptom complex is essential. Hyperactive response to carotid sinus stimulation is defined as asystole due either to sinus arrest or AV block of more than 3 seconds and/or a substantial symptomatic decrease in systolic blood pressure. However, such heart rate and hemodynamic re- ASSESSING MEDICAL TECHNOLOGY sponses may occur in normal subjects and patients with coronary artery disease (42,43), and a conclusion of a cause and effect relation between the hypersensitive carotid sinus and the patient's symptoms must be made with great caution. Minimal pressure on the carotid sinus in the elderly or pa- tients receiving digitalis may result in marked changes in heart rate and blood pressure, yet not be of clinical signif- icance. Permanent pacing for patients with pure excessive card~oinhibitory response to carotid stimulation is effective in relieving symptoms (44-46). Since 10 to 20% of patients with this syndrome may have an important vasodepressor component, it is necessary to define this before concluding that all symptoms are related to asystole alone. In patients with both cardioinhibitory and vasodepressor components, attention to the latter in patients undergoing permanent pac- ing is essential for effective therapy. Indications for Permanent Pacing in Hypertensive Carotid Sinus Syndrome Class I. A. Patients with recurrent syncope associated with clear, spontaneous events provoked by carotid sinus stim- ulation, in whom minimal carotid sinus pressure in- duces asystole of greater than 3 seconds in the ab- sence of any medication that depresses the sinus node or AV conduction. Class II. A. Patients with recurrent syncope without clear, pro- vocative events and with a hypersensitive cardioin- hibitory response. Class III. A. Asymptomatic patients with a hyperactive cardioin- hibitory response to carotid sinus stimulation. B. Patients with vague symptoms, such as dizziness and/ or light-headedness, and with hyperactive cardioin- hibitory response to carotid sinus stimulation. C. Patients with recurrent syncope, light-headedness or dizziness in whom the vasodepressor response is the cause for symptoms. VII. The Use of Pacemakers in Children Although the indications for pacemakers in children are similar to those in adults, there are some special consid- erations. The optimal indication for a pacemaker implan- tation in a child, as in an adult, is the concurrent observation of symptoms with bradycardia. For example, a patient with syncope who is observed electrocardiographically to have complete AV block or a patient with syncope who is noted on physical examination to have severe bradycardia such as a heart rate of 30 beats/mint Concurrence of symptoms and bradycardia can also be obtained by 24 hour ambulatory electrocardiography or by transtelephonic electrocardiog- raphy. Sometimes several 24 hour recordings are necessary.

APPENDIX A: PROFILES Sinus node dysfunction (sick sinus syndrome), although becoming more frequently recognized in pediatric patients, is not in and of itself an indication for pacemaker implan- tation. In patients with sinus node dysfunction. even greater emphasis is placed on concurrence of sinus bradycardia or exit block with symptoms. Sinus node dysfunction is not likely to be a fatal arrhythmia in infants or children. There- fore, more time can be spent trying to document the presence .of an arrhythmia during symptoms. Symptomatic bradycardia (as defined in the Introduction) with sinus node dysfunction is considered to be an indication for a pacemaker, assuming that another etiology to account for such symptoms has been excluded. Such alternate etiol- ogies to be considered include seizures resulting in hypoxia, breathholding or infantile apnea. It is sometimes hard to differentiate whether apnea or bradycardia occurs first in symptomatic patients. The brady- cardia-tachycardia syndrome is frequently an indication for pacemakers in children, particularly if an antiarrhythmic . .. .. .. .. .. drug other than digitalis is necessary. It appears that the use of quinidine or other type I drugs is particularly dangerous in children with bradycardia-tachycardia syndrome. Pro- pranolol and amiodarone also severely depress sinus node function and their use may require the use of a pacemaker in children with the bradycardia-tachycardia syndrome. Indications for Permanent Pacing in Children Class I. A. Second or third degree AV block with symptomatic bradycardia as defined. B. Advanced second or third degree AV block with moderate to marked exercise intolerance. C. External ophthalmoplegia with bifascicular block (47). D. Sinus node dysfunction with symptomatic bradycar- dia as defined. E. Bradycardia-tachycardia syndrome in a child with a need for antiarrhythmic drugs other than digitalis. F. Congenital AV block with wide QRS escape rhythm (48). G. Asymptomatic patients after cardiac surgery with ad- vanced second or third degree AV block persisting 10 to 14 days postoperatively (49). Class II. A. Second or third degree AV block within the bundle of His in an asymptomatic patient (49). B. Prolonged subsidiary pacemaker recovery time (50). C. Transient surgical second or third degree AV block, which reverts to bifasicular block. D. Asymptomatic children with second or third degree AV block and a ventricular rate of less than 45 beats/ min when awake (51). E. Asymptomatic infra-His, second or third degree AV block (49). 271 F. An asymptomatic neonate with congenital complete heart block with bradycardia in relation to age (52). Complex ventricular arrhythmias associated with sec- ond or third degree AV block or sinus bradycardia (53) Class III. A. Postoperative bifascicular block in the asymptomatic patient. B. Postoperative bifascicular block with first degree AV block in the asymptomatic patient. Transient surgical AV block that returns to normal conduction in less than I week. D. Asymptomatic type I second degree AV block. E. Asymptomatic congenital heart block without pro- found bradycardia in relation to age. VIII. Pacing for Tachyarrhythmias The use of implantable cardiac pacemakers to terminate supraventricular or ventricular tachycardias is just begin- ning. We will not discuss the use of overdrive pacemakers for the termination of ventricular tachycardia, since there is no clinically approved device for this indication and since the use of this device is still extremely controversial with . . . . . . . ~ . . _ . risks perhaps outweighing benefits In some patients. the decision for chronic use of a pacemaker to control tachy- cardias should be made only after careful observation and electrophysiologic study by those experienced in this com- plex field. Indications for Permanent Pacing for Tachyarrhythmias Class I. A. Patients with symptomatic supraventricular tachy- cardia which has not responded to a well planned medical regimen including documentation of ade- quate serum drug concentrations, or in whom the medical treatment causes major side effects or in whom the necessity for taking drugs seriously inhibits the patient's ability to carry out normal daily func- tion. Before implantation of an antitachycardia pace- maker. an electrophysiologic study should be carried out and the various proposed modes of termination of tachycardia tested to determine which one is most anorc)nriate for the particular patient An external —rr--r-- - -- --- ---- r—------ - - r—------- ---- -------- - - form of the implantable device should be available during electrophysiologic study to document the ex- act settings that will be used and will in fact terminate the patient's tachycardia. The physician who im- plants the pacemaker should be prepared to repro- gram the pacemaker to new settings when the patient . . . Is again active.

272 Class II. None. Class III. A. Patients with pre-excitation in whom atrial fibrillation with rapid ventricular response has occurred spon- taneously or during electrophysiologic testing. IX. Clinical Applications of Various Pacing Modes This section lists the conditions for which various pacing modes might be selected. The acceptability of a given mode of pacing is divided into three classes according to the fol- lowing definitions: Class 1: Conditions for which there is general agreement that such a mode of pacing is appropriate. Class 11: Conditions for which a given mode of pacing may be used, but there is divergence of opinion with respect to the necessity of that mode of pacing. Class 111: Conditions for which there is general agree- ment that such a mode of pacing is . . Inappropriate. Two varieties of pulse generators are available for per- manent implantation: 1) single chamber pacemakers (SCP) for use in either atrium or ventricle; and 2) dual chamber pacemakers (pop) for use in both cham- bers (usually programmable to SCP modes as well). Virtually all modern pacemakers are multiprogramma- ble, which renders them more or less adaptable to changing clinical situations. Some pacing modes that were originally found as specific pacemaker models (such as VOO, VAT and VVT) are not discussed. * These modes are now optional settings of multiprogrammable pacemakers. Many new pacemakers also provide telemetry of stored and variable data that, on command, can provide information about pace- maker function and clinical performance. Both program- mability and telemetry are helpful in optimizing pacemaker function, avoiding reoperation and extending pulse gener- ator life. It is essential that the selection process be indi- vidualized to the needs of the patient, with appropriate con- sideration given to complication, complexity and cost. Single Chamber Pacemakers 1. Aerial (AAI): Atrial pacing inhibited by sensed atrial activity. Class I. A. Symptomatic sinus node dysfunction (sick sinus syndrome), provided AV conduction is shown to be adequate by appropriate tests. *The pacemaker mode is identified according to the Inter-Society Com- mission for Heart Disease Resources (ICHD) code ( I ). ASSESSING MEDICAL TECHNOLOGY Class II. A. Overdrive of supraventricular or ventricular arrhythmias. B. Hemodynamic enhancement through rate adjust- ment in patients with bradycardia and symptoms of impaired cardiac output. Class III. A. Pre-existing AV conduction delay or block or if PR interval is inappropriately prolonged by atrial pacing. B. Inadequate intracavitary atrial complexes. 11. Ventricular (Wl): The classic prototypical pacing mode; ventricular pacing inhibited by sensed spontaneous ventric- ular activity. Class I. A. Any symptomatic bradyarrhythmia, but particu- larly when there is: 1) no significant atrial hemodynamic contribution (atrial flutter/fibrillation, giant atria), or 2) no evidence of pacemaker syndrome due to loss of atrial contribution or negative atrial kick (a replacement pacemaker)~. Class II. A. Symptomatic bradycardia, where pacing simplicity is a prime concern, in cases of: 1) senility (life-sustaining only), 2) terminal disease, 3) domicile remote from a follow-up center, or 4) intact retrograde VA (ventriculoatrial) conduction. Class III. A. Known pacemaker syndrome (a replacement pace- maker) or symptoms produced by temporary ven- tricular pacing at the time of initial pacemaker implantation. B. The need for maximal atrial contribution, because of: 1. congestive heart failure, or 2. special need for rate responsiveness. Dual Chamber Pacemakers 1. VDD: Ventricular pacing in synchrony with sensed atrial activity, inhibited by sensed ventricular activity. (Although these units are rate-responsive, at a slow atrial rate below the set rate of the pacemaker only the ventricle is paced, in which case the pacemaker functions as a VVI unit.) fThe pacemaker syndrome was first defined as the light-headedness or syncope related to long cycles of AV asynchrony that occurred at times during VV! or VOO pacing. The definition is now expanded to include: ~ ) episodic weakness or syncope associated with alternating AV synchrony and asynchrony; 2) inadequate cardiac output associated with continued absence of AV synchrony or with fixed asynchrony (persistent VA con- auction); and 3) patient awareness of beat to beat variations in cardiac contractile sequence, often as a result of: a) cannon A waves; b) V waves transmitted to the atria or pulmonary veins; and c) bundle branch block patterns of ventricular contraction with a paced beat.

APPENDIX A: PROFILES Class I. A. Requirements far ventricular pacing when adequate atrial rater; and adequate intracavitary atrial com- plexes are present. This includes the presence of complete AV block in patients: 1) requiring atrial contribution for hemodynamic benefit. or 2) with previous or anticipated pacemaker syndrome. Class 11. A. Normal sinus rhythm and normal AV conduction in patients needing ventricular pacing intermittently. Class III. A. Frequent or persistent supraventricular tachyar- I. rhythmias, including atrial fibrillation or flutter. B. Inadequate intracavitary atria! complexes. 2. 11. DVI: Pacing of both chambers at ~ preselected minimal rate, inhibited by ventricular but not atrial activity. 3 Class I. A. The need for synchronous Trial-ventricular con- traction in patients with symptomatic bradycardia and a slow atrial rate. B. Patients with previously documented pacemaker syndrome. Class II. A. Overdrive of certain arrhythmias. B. Frequent siupraventricular arrhythmias in which combined pacing and drugs have been shown to be therapeutically effective. C. Bradycardia-tachycardia >;yndrome. provided ad- justment of atrial rate and AV interval terminates; or prevents the emergence of supraventricular ar- rhythmias with or without concomitant drug administration. Class III. A. Frequent or persistent supraventricr~lar tachyar- rhythmia~;, including atrial fibrillation or flutter. 111. 000: Pacing of both chambers, ~ien~;ing of both cham- bers, inhibition of atrial or ventricular output by sensed atrial or ventricular activity; tri~g,gerin~~ of ventricular output by sensed atrial activity. Class I. A. Requirement for AV synchrony over ~ wide range of rates such as: 1. the active or young patient with atrial rates re- sponsive to clinical need, 2. significant hemodynamic need, and 3. pacemaker syndrome during previous pace- maker experience, or a reduction in systolic blood pressure of more than 20 mm His during ven- tricular pacing at the time of pacemaker im- plantation (with or without evidence of VA conduction). Class II. A. Complete heart block or sick sinus syndrome and stable atrial rates. 273 B. Any patient in whom simultaneous control of atrial and ventricular rates inhibits tachyarrhythmias or in whom the pacemaker can be adjusted to a mode designed to interrupt the arrhythmia. Class III. A. Frequent or persistent supraventricular tachyar- rhythmias, including atrial fibrillation or flutter. B. Inadequate intracavitary atrial complexes. References Pacemaker study gr<,up. Pars`'nne' V. Furman S. Smyth PD. et al. Optimal resources tier implantable cardiac pacemal;ers. Circulation 1 9X3 ;6X :225 A-44A. Friedberg CK. D<~noso E. Stein WB. Nonsu :ical acquired heart block. Ann NY Acad Sci 1964;1 1 1 :833-47. Gadboys HL, Wisoff BG, Litwak RS. Surf gal treatment of complete heart block: an analysis of 36 cases. JAM! 1964;189:97-102. 4. Donmoyer TL. DeSanctis RW, Austen \? G. Experience with im- plantable pacemakers using myocardial elec rodes in the management of heart block. Ann Thorac Surg 1967;3:21 '-27. 5. EdhaL: O. Swahn A. Prognosis of patients with complete heart block or arrhythmic syncope who were not treated with artificial pacemakers: a long-term follow-up study of 101 patients. Acta Med Scand 1 976;200:457-63. 6. Dhingra RC, Denes P. Wu D, Chuquimia R. Rosen KM. The sig- nificance of second degree atrioventricular block and bundle branch bk>ck: observations regarding site and type of block. Circulation 1 974:49:63X-46. 7. Strasberg 13, Amat-Y-Leon F. Dhingra RC, et al. Natural history of chronic second-degree atrioventricular nodal block. Circulation 198 1 ;63: 1043-9. 8. Donoso E. Adler LN, Friedberg CK. Unusual forms ot second-degree atrioventricular block, including Mobit% type 11 block, associated with the Morgagni-Adams-Stokes syndrome. Am Heart J 1964;67:150-7. 9. Ranganathan N. Dhurandhar R. Phillips JH. Wigle ED. His bundle electrogram in bundle-branch block. Circulation 1972:45:282-94. 10. Ginks WR. Sutton R. Oh W. Leatham A. Long-term prognosis after acute anterior infarction with atrioventricular bk>ck. Br Heart J 1 977;39: 1 86-9. 11. Col IJ. Weinberg SL. The incidence and mortality of intraventricular conduction defects in acute my`'cardial infarction. Am I Cardi<,l 1 972:29:344-50. 12. Hindman MC. Wagner GS. JoRo M, et al. The clinical significance elf bundle branch block c`,mplicatinL: acute myocardial infarction. 2. Indications for temporary and permanent pacemaker insertion. Cir- culation 197X;58:689-99. 13. Ritter WS, Atkins JM, Blomqvist CG, Mullins CB. Permanent pacing in patients with transient trifascicular block during acute myocardial int:arcti<,n. Am J Cardiol 1976;38:205-8. 14. Domenighetti G. Perret C. Intraventricular conduction disturbances in acute myocardial infarction: short- and long-term prognosis. Eur J Cardiol 1980;1 1 :51-9. 15. Penton GB, Miller H. Levine SA. Some clinical features off complete heart block. Circulation 1956;13:801-24. 16. 17. Fisch GR, Zipes DP, Fisch C. Bundle branch block and sudden death. Prog Cardiovasc Dis 1980;23: 187-224. Dhin*gra RC, Denes P. Wu D, et al. Syncope in patients with chronic bifascicular block. Significance, causative mechanisms, and clinical implications. Ann intern Med 1974;81:302-6. 18. DePasquale NP, Bruno MS. Natural history of combined right bundle branch block and left anterior hemiblock (bilateral bundle branch block). Am J Med 1973;54:297-303.

274 19. Peters RW, Scheinman MM, Modin G. O'Young I, Somelofski CA, Miles C. Prophylactic permanent pacemakers for patients with chronic bundle branch block. Am I Med 1979;66:978-85. 20. Spurrell RAI, Smithen CS, Sowton E. Study of right bundle-branch block in association with either left anterior hemiblock or left posterior hemiblock using His bundle electrograms. Br Heart I 1972;34:800- 6. 21. Kulbertus H. Collignon P. Association of right bundle-branch block with left superior or inferior intraventricular block: its relation to complete heart block and Adams-Stokes syndrome. Br Heart I 1 969;3 1 :435-40. 22. McAnulty IH, Rahimtoola SH, Murphy ES, et al. Natural history of "high risk'' bundle-branch block: final report of a prospective study. N Engl 1 Med 1982;307:137-43. 23. Scheinman MM, Peters RW, Modin G. Brennan M, Mies C, O'Young I. Prognostic value of infranodal conduction time in patients with chronic bundle branch block. Circulation 1977;56:240-4. 24. McAnulty IH, Kauffman S. Murphy E, Kassebaum DO, Rahimtoola SH. Survival in patients with intraventricular conduction defects. Arch Intem Med 1978;138:30-5. 25. Denes P. Dhingra RC, Wu D, Wyndham CR, Anat-y-Lean F. Rosen KM. Sudden death in patients with chronic bifascicular block. Arch Intern Med 1977;137:1005-10. 26. Vera Z. Mason DT, Fletcher RD, Awan NA, Massumi RA. Prolonged His-Q interval in chronic bifascicular block relation to impending complete heart block. Circulation 1976;53:46-55. 27. Narula OS, Gann D, Samet P. Prognostic value of H-V intervals. In: Narula OS, ed. His Bundle Electrocardiography and Clinical Electro- physiology. Philadelphia: FA Davis, 1975:437-49. 28. Denes P. Dhingra RC, Wu D, et al. H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemi- block): clinical, electrocardiographic and electrophysiologic correla- tions. Am I Cardiol 1975;35:23-9. 29. Probst P. Pachinger O. Murad AA, Leisch F. Kandl F. The HQ time in congestive cardiomyopathies. Am Heart I 1979;97:436-41. 30. Rosen K, Dhingra R. Wyndham C, Bauernfeind R. Sirym S. Denes P. Significance of atrial pacing induced block in the His-Purkinje system in patients with chronic bifascicular block (abstr). Am I Cardiol 1979;43:400. 31. Cheng TO. Atrial pacing: its diagnostic and therapeutic applications. Prog Cardiovasc Dis 1971;14:230-47. 32. Gupta PK, Lichstein E, Chadda KD. Intraventricular conduction time (H-V interval) during antegrade conduction in patients with heart block. Am 1 Cardiol 1973;32:27-31. 33. Altschuler H. Fisher ID, Furman S. Significance of isolated H-V interval prolongation in symptomatic patients without documented heart block. Am Heart I 1979;97: 19-26. 34. Dhingra RC, Palileo E, Strasberg B. et al. Significance of the H-V interval in 517 patients with chronic bifascicular block. Circulation 1981;64:1265-71. 35. Meytes 1, Kaplinsky E, Yahini IH, Hanne-Papara N. Neufeld HN. Wenckebach A-V block: a frequent feature following heavy physical training. Am Heart I 1975;90:42~30. ASSESSING MEDICAL TECHNOLOGY 36. Talan DA, Bauernfeind RA, Ashley WW, Kanakis C Jr, Rosen KM. Twenty-four hour continuous ECG recordings in long-distance run- ners. Chest 1982;82:19-24. 37. Dreifus LS, Michelson EL, Kaplinsky E. Bradyarrhythmias: clinical significance and management. I Am Coll Cardiol 1983;1:327-38. 38. Rasmussen K. Chronic sinus node disease: natural course and indi- cations for pacing. Eur Heart I 1981;2:455-9. 39. Shaw DB, Holman RR, Gowers II. Survival in sinoatrial disorder (sick-sinus syndrome). Br Med I 1980;280:139-41. 40. Rubenstein JI, Schulman CL, Yurchak PM, DeSanctis RW. Clinical spectrum of the sick sinus syndrome. Circulation 1972;46:5-13. 41. Kay R. Estiok M, Wiener I. Primary sick sinus syndrome as an indication for chronic pacemaker therapy in young adults: incidence, clinical features, and long-term evaluation. Am Heart I 1982;103:338- 42. 42. Heidorn GH, McNamara AP. Effect of carotid sinus stimulation on the electrocardiograms of clinically normal individuals. Circulation 1956;14:1 104-13. 43. Brown KA, Maloney ID, Smith HC, Hartzler GO, Ilstrup DM. Carotid sinus reflex in patients undergoing coronary angiography: relationship to degree and location of coronary artery disease in response to carotid sinus massage. Circulation 1980;62:697-703. 44. Walter PF, Crawley IS, Dorney ER. Carotid sinus hypersensitivity and syncope. Am I Cardiol 1978;42:396-403. 45. Peretz DI, Gerein AN, Miyagishima RT. Permanent demand pacing for hypersensitive carotid sinus syndrome. Can Med Assoc I 1973;108:1 131-4. 46. Chughtai AL, Yans I, Kwatra M. Carotid sinus syncope: report of two cases. IAMA 1977;237:2320-1. 47. Morriss IH, Eugster GS, Nora II, Pryor R. His bundle recording in progressive external ophthalmoplegia. I Pediatr 1972;81: 1 167-70. 48. Pinsky WW, Gillette PC, Garson A Jr, McNamara W. Diagnosis, management, and long-term results of patients with congenital com- plete atrioventricular block. Pediatrics 1982;69:728-33. Gillette PC. Recent advances in mechanisms, evaluation, and pace- maker treatment of chronic bradydysrhythmias in children. Am Heart 1 1981;102:920-9. 49. 50. Benson DW Jr, Spach MS, Edwards SB, et al. Heart block in children. Evaluation of subsidiary ventricular pacemaker recover times and ECG tape recordings. Pediatr Cardiol 1982;2:39-45. 51. Karpawich PP, Gillette PC, Garson A Jr, Hesslein PS, Porter C, McNamara W. Congenital complete atrioventricular block: clinical and electrophysiologic predictors of need for pacemaker insertion. Am 1 Cardiol 1981;48: 1098-102. 52. Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. Cardiovasc Clin 1972;4:85- 101. 53. Winkler RB, Freed MD, Nadas AS. Exercise-induced ventricular ec- topy in children and young adults with complete heart block. Am Heart 1 1980;99:87-92.

Clinical Efficacy Assessment Project American College of Physicians Department of Health and Public Policy 4200 Pine Street Philaclelphia, PA 19104 (215) 243 1200 Major Emphases of Technology Assessment Activities Concerns Safety Technology Drugs Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit _ _ X _ Ethical/Legal/ S· 1 ocla1 Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded Application of Technologies X Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $160,000 * Some CEAP evaluations note comparative costs of procedures, but cost analy- ses are not conducted. AMERICAN COLLEGE OF PHYSICIANS CLINICAL EFFICACY ASSESSMENT PROJECT Introduction The Clinical Efficacy Assessment Project (CEAP) is a medical technology evaluation program of the American College of Physi- cians (ACP). The ACP is a 60,000-member national medical specialty society for in- ternists and related subspecialists. CEAP is an expansion of the college's par- ticipation in the Blue Cross and Blue Shield 275 Association's Medical Necessity Project for evaluating the appropriateness of medical procedures, begun in 1976. In early 1981 the project was renamed the Clinical Efficacy Assessment Project and expanded with the as- sistance of a 3-year grant from the John A. Hartford Foundation. The Hartford Foun- dation support ended in July 1984. CEAP is now fully supported by the ACP. Since 1976, ACP has conducted approxi- mately 100 evaluations through the Medical Necessity Project (jointly with Blue Cross and Blue Shield) and CEAP (beginning in 1981~.

276 From 1981 through 1984, CEAP activities have included evaluation, approval, and dis- semination of recommendations of over 60 procedures and tests. Purpose The purpose of CEAP is to help physicians practice high-quality, more-efficient, and cost-effective medicine. CEAP recommenda- tions provide physicians with current infor- mation and guidelines regarding the use of tests, procedures, and therapies and the ra- tionale for such recommendations founded on both the literature and broad-based expert opinion. CEAP's specific objectives are to 1. expand and refine the methods of inves- tigation used under the (Blue Cross and Blue Shield Association) Medical Necessity Proj- ect; 2. coordinate the collection, analysis, and dissemination of expert opinion and informa- tion obtained from analyses of data to the ACP membership and other interested orga- . . nlZatlOIlS- r 1l ~ rollowln~ sources: 3. utilize an explicit and scientific data- based method for assessing the safety, effi- cacy, and clinical effectiveness of medical tests and procedures; 4. develop new methods for assessing the safety, efficacy, and clinical effectiveness of medical tests and procedures; 5. study the work of other organizations engaged in similar pursuits throughout the world; and 6. evaluate the impact of CEAP recom- mendations on costs and use of these medical tests, procedures, and therapies. Subjects of Assessment CEAP evaluates medical tests, procedures, and therapeutic interventions within the pur- view of internal medicine and/or its certified subspecialties, e.g., gastroenterology, cardi- ology, and oncology. Stage of Diffusion CEAP evaluates established technologies, particularly when newly available informa- ASSESSING MEDICAL TECHNOLOGY tion indicates that changes in patterns of use might be appropriate. CEAP evaluates new technologies only where data adequate for evaluation are available. It may, however, recommend that appropriate studies be con- ducted. Concerns CEAP evaluates the safety, efficacy, effec- tiveness, appropriate use, and relative costs of technologies. Where appropriate and pos- sible, the project also considers broader soci- etal implications of technologies. Evaluations may include comparisons of procedures or tests, and some evaluations include cost in- formation where it may affect use of proce- dures. CEAP findings do not include reim- bursement recommendations. The CEA Subcommittee will identify tech- nologies that are potential candidates for CEAP evaluations through one or more of the 1. Internally generated by the CEA Sub- committee by reviewing policy needs, practi- tioner opinion, academic opinion, recent journal articles, and professional meetings. 2. Recommendations and requests from other ACP committees. 3. Requests by outside organizations. ACP has considered requests for technol- ogy assessment from government agencies, Blue Cross and Blue Shield, other private in- surance companies, the Council of Medical Specialty Societies, other medical specialty societies, ACP committees, and ACP mem- bers and fellows. Selection Assessment topic selection decisions are made by the CEA Subcommittee, following screening by the CEAP staff. The major cri- teria for CEAP selection of technologies are the following: 1. Degree of interest to practitioners of in- ternal medicine, whether or not internists are directly responsible for its application.

APPENDIX A: PROFILES 2. Potential for wide application or exist- ing high prevalence of use. 3. Potential for significant benefit if widely applied. 4. Potential for risk if widely applied, par- ticularly in relation to potential for benefit. In addition, the CEA Subcommittee will consider the feasibility of undertaking an evaluation based on staff capabilities and ACP resources and whether sufficient data are available for evaluation. CEAP indicates that these selection crite- ria should be viewed as guidelines only; there may be instances in which the CEA Subcom- mittee will elect to undertake an assessment for other reasons, such as the request of an agency of government or of another profes- sional body. Process The evaluation process is as follows (CEAP Procedural Manual, 1983~: 1. Evaluation is announced, comments in- vited. Notices of an impending CEAP evalua- tion are published in the Annals of Internal Medicine, the New England Journal of Medi- cine, and the ACP Observer. The notices in- vite interested parties to send in comments. For special or major evaluations, other spe- cialty journals may be asked to publish no- tices of CEAP evaluations. 2. Staff conducts literature review. The CEAP staff, in consultation with the CEA Subcommittee, selects the appropriate mem- ber societies of the Council of Subspecialty Societies (CSS) and the Council of Medical Societies (CMS) (these are advisory councils to the College's Board of Regents) to review the technology in question. These societies are asked to provide opinion and data on the safety, efficacy, effectiveness, and cost of the technology, as well as to identify other ex- perts (proponents, opponents, and those who are neutral on the topic) to provide ~nforma- tion on the technology. Data and expert opinion may be solicited from experts recom- mended by the CSS and CMS societies, the CEA Subcommittee, and the CEAP staff. 3. Consultants and/or physician staff draft statement. CEAP staff or outside con- 277 sultants analyze the literature, review assess- ments of other organizations, and obtain the opinions of the CSS/CMS members and other experts. CEAP staff or consultants synthesize this information into a draft statement. The draft statement includes a description of the technology and its intended purpose; sum- maries of the clinical efficacy and effective- ness of the technology; and its safety, appro- priate use, and relative costs. Areas requiring further research are also summarized. When necessary, a detailed background paper doc- umenting the conclusions in the summary statement is developed. 4. Draft statement reviewed by outside experts, including pro, con, and neutral. The draft statement (including background pa- pers, if any) is submitted to the CEA Sub- committee for its initial review. Following this, the draft statement is sent back to the representatives of CSS, CMS, and the con- sulting societies and experts for review. In addition, experts from among those who re- view Annals of Internal Medicine manu- scripts as well as other identified experts may be asked to review the proposed statement. Attempts are made in each case to identify and ask the opinions of both proponents and opponents of the technology. 5. Statement amended. CEAP staff or outside consultants amend the draft based upon review by the CEA Subcommittee and outside experts. 6. Statement reviewed/approved by CEA Subcommittee. The draft statement is re- presented to the CEA Subcommittee along with the following information: a. the name of the requesting agency, date of request, dates for the approval to evaluate and for the completion of the evaluation, and the name of the principal author of the statement; b. the names of the consulting organi- zations and experts, c. the consultants' statements; d. identification of differences of opin- ion and justification of the proposed CEAP statement when consensus has not been achieved. 7. Statement reviewed/approved by ACP Health and Public Policy Committee. Fol-

278 lowing CEA Subcommittee approval, the draft statement is presented to the ACP Health and Public Policy Committee (HPPC) for approval. 8. Statement reviewed/approved by ACP Board of Regents. Following HPPC ap- proval, the draft statement is presented to the Executive Committee of the Board of Regents for approval. The HPPC and the Executive Committee also receive a summary of the process used in formulating the CEAP state- ment. CEAP statements range from one para- graph to 10 pages in length. CEAP state- ments do not have a set format or explicit categories for evaluation findings or recom- mendations. Statement format depends on the nature of the particular technology evalu- ated. Generally, however, CEAP evaluation statements include guidelines directed to the clinician which specify the circumstances for which the tests or procedures are indicated, not indicated, or contraindicated. Guidelines usually identify areas where data are inade- quate to permit any authoritative recommen- dation, and recommendations generally specify the nature of research necessary to re- solve controversial issues. ACP does not itself sponsor or undertake clinical trials/research. Assessors CEAP evaluations are conducted in a co- operative effort of the CEA Subcommittee, outside experts, and CEAP staff, as described above under Process. The six-member CEA Subcommittee that governs CEAP has expe- rience in medicine, clinical epidemiology, statistics, decision analysis, technology as- sessment, economics, and public policy. CEA Subcommittee members are appointed by the Chairman of the ACP Board of Regents, sub- ject to approval by the board, for 1-year terms, and they may be reappointed. From 1978 to 1980, the ACP Medical Prac- tice Committee responded to Blue Cross and Blue Shield Medical Necessity requests re- garding appropriateness of procedures. In 1981, that committee coordinated CEAP ac- tivities. Beginning in 1982, the ACP estab- lished the CEA Subcommittee. ASSESSING MEDICAL TECHNOLOGY Turnaround Most CEAP evaluations are completed within 6 to 9 months of selection for evalua- tion. Reporting Approved CEAP statements appear in press releases. All CEAP statements are sum- marized in the ACP Observer, and some are published in full in the Annals of Internal Medicine. Statements and background papers are disseminated to the medical com- munity (ACP membership, medical organi- zations, practicing physicians, medical jour- nals, and the medical educational system), reimbursers, and other policymakers. State- ments are also available to the public. Private letters are sent to the original questioner. Ta- ble A-1 lists the CEAP evaluation statements issued since 1981. Impact The CEAP grant from the Hartford Foun- dation included an agreement with the Blue Cross and Blue Shield Association to evaluate the impact of CEAP recommendations. The purposes of this study are to discover the im- pact of CEAP on other organizations and how the recommendations affect physician behavior and health care costs. The results of the organizational survey show that all 50 CEAP statements issued between 1981 and 1983 were used for educational and/or pol- icy-setting purposes. None of the 238 respon- dents stated disagreement with the recom- mendations or found them to be unhelpful. The protocol for measuring the impact of CEAP statements on health care costs is cur- rently being designed. In its final report to the Hartford Founda- tion, ACP concluded that CEAP enabled the College to (1) design a workable and credible system for evaluating technologies; (2) dem- onstrate that a professional society can assess the practices of its members and achieve their acceptance of the assessments; (3) stimulate other organizations' involvement in CEAP and in the development of their own assess- ment projects; and (4) develop the protocol

APPENDIX A: PROFILES TABLE A-1 Approved CEAP Recommendations, 1981 through early 1985 1981 1. Ultrasonic arteriography 2. Use of ultrasonic arteriography in distinguishing diseases of the carotid artery system 3. Gastric analysis by the capsule method (Heidelberg) 4. Intracutaneous titration 5. Estrogen pellet implantation 6. Management of histapenia 7. Activated prothrombin complex concentrate in patients with hemophilia A and inhibitor antibodies to factor VIII 8. Human tumor cell drug sensitivity assay in the treatment of solid tumors 9. 24-hour sphygmomanometry 10. Ergonovine provocative testing (reconsidered in 1983) 11. Percutaneous transiuminal coronary angioplasty (reconsidered in 1983) 12. 25 hydroxyvitamin D level test 13. Intravenous histamine therapy 14. Hyperbaric oxygen therapy in the treatment of arthritis 15. Pneumococcal vaccine 1982 16. Phonocardiography 17. Cardiokymography 18. Antilymphocyte and antithymocyte globulin in renal transplantation 19. Hyperbaric oxygen therapy in the treatment of actinomycosis 20. Hyperbaric oxygen therapy in the treatment of chronic osteomyelitis 21. Immunotherapy of cancer 22. Bentonite flocculation test 23. DNA antibody test 24. Kunkel test (total serum gamma globulin) 279 Respiratory therapy modalities: 25. Intermittent positive pressure breathing 26. Incentive spirometry 27. Postural drainage with or without chest wall manipulation 28. Aerosol therapy 29. Oxygen therapy 1983 Breath tests for diagnosing digestive disorders: 30. Breath hydrogen lactose intolerance test for diagnosing lactose 31. Lactulose breath test for small intestinal transit time and small intestinal overgrowth 32. i3CO2 breath test for diagnosing fat maldigestion and malabsorption 33. i3CO2 breath test for diagnosing bile acid malabsorption 34. Hyperbaric oxygen therapy of chronic and acute peripheral vascular insufficiency 35. Hyperbaric oxygen therapy in treatment of acute, traumatic peripheral ischemia 36. Hyperbaric oxygen therapy in the treatment of senility Selected methods for the management of diabetes mellitus: 37. Computerized blood glucose insulin infusion devices 38. External infusion pump for treatment of diabetes 39. Home blood glucose monitoring 40. Pancreas transplantation for treatment of diabetes mellitus 41. Automated ambulatory blood pressure monitoring 42. Hepatitis B vaccine 43. Topical oxygen therapy for the treatment of decubitus ulcers 44. Ergonovine provocative testing for coronary artery spasm (supersedes 1981 recommendation) 45. Dexamethasone suppression test for the detection, diagnosis, and management of depression 46. Implantable and external infusion pumps for the treatment of thromboembolic disease in outpatients

280 TABLE A-1 Continued ASSESSING MEDICAL TECHNOLOGY Percutaneous transluminal ang~oplasty: 47. Coronary arteries (supersedes 1981 recommendation) 48. Iliac, femoral, popliteal arteries 49. Renal arteries 50. Carotid, vertebral, subelavian arteries 1984 51. Apheresis in the treatment of chronic, severe rheumatoid arthritis (supersedes 1980 recommendation) 52. Diagnostic endocardial electrical recording and stimulation 53. Endoscopic sclerotherapy of esophageal varices 54. Radiologic methods to evaluate bone mineral content 55. Endoscopic retrograde cholangiopancreatography (ERCP) 56. Glycosylated hemoglobin assays in the management of diabetes mellitus 57. Biofeedback for gastrointestinal disorders 58. Biofeedback for headaches 59. The use of diagnostic tests for screening and evaluating breast lesions 60. Endoscopy in the evaluation of dyspepsia 1985 61. Biofeedback for hypertension 62. Biofeedback for neuromuscular disorders 63. Colonoscopy: management of colorectal neoplasia 64. The safety and efficacy of ambulatory cardiac catheterization in the hospital and free-standing setting (super- sedes 1980 recommendation) 65. I~ithotripsy 66. Pneumococcal vaccine (supersedes 1981 recommendation) 67. Diagnostic spinal tap 68. Diagnostic thoracentesis and pleural biopsy 69. Apheresis for chronic inflammatory demyelinating polyneuropathy and renal transplantation 70. Automated ambulatory blood-pressure monitoring 71. Cardiokymography (supersedes 1982 recommendation) for a network of physicians to collect data on their actual use of tests, procedures, and ther- ap~es. Reassessment At intervals following approval of a CEAP statement, staff members accept comments and solicit advice from the relevant CSS/ CMS members and/or other experts as to the availability of any important new informa- tion on the technology previously reviewed. If substantive new information is available, the CEA Subcommittee will consider re- evaluating the topic. The CEA Subcommit- tee also considers requests from ACP mem- bers and others for re-evaluation of a state- ment when the request is accompanied by compelling documentation. Re-evaluation is subject to the process described above. The following are examples of technologies reas- sessed by CEAP. · Cytotoxic food testing was determined in a 1979 CEAP statement to have no scien- tific basis. In 1981 CEAP found it to be as yet unproven and requiring further testing. · Ergonovine provocative test was consid- ered in 1981 to be standard and efficacious clinically when performed in a cardiac cathe- terization laboratory in patients who do not have documented fixed coronary obstructive lesions at angiography. In 1983 the CEAP statement notes that while the procedure in- volves serious potential risks and thus is gen- erally performed in a cardiac catheterization

APPENDIX A: PROFILES laboratory, it may also be safely done in a critical care unit in carefully selected patients who are treated strictly according to a well- tested protocol. · Percutaneous transluminal angioplasty for coronary arteries (PICA) was found in 1980 to be an investigative procedure. In a 1983 statement, CEAP suggests that PICA is an alternative to coronary artery bypass graft surgery in patients with high-grade stenosis (greater than 50 to 70 percent) confined to a single coronary artery and limiting anginal symptoms despite an adequate trial of medi- cal treatment. · Plasmapheresis in the management of rheumatoid arthritis did not meet the stan- dards of clinical efficacy according to a 1980 CEAP statement that indicated it should be performed only as part of a disciplined clini- cal investigative effort. In 1984 CEAP again found apheresis for rheumatoid arthritis to be investigational, though patients with life- threatening rheumatoid vasculit~s may be can- didates for a trial course of plasmapheresis. Funding/Budget The John A. Hartford Foundation grant for the support of the CEAP demonstration project was $650,412 over 3.5 years, from January 1981 through July 1984. The approx- 281 imate 1985 budget for the program is $160,000. Regardless of further foundation support, ACP is committed to continuing CEAP. No charges are made for CEAP evalu- ations. Example On the following pages is the 1984 CEAP recommendation on endoscopy in the evalua- tion of dyspepsia. The recommendation was published in the Annals of Internal Medi- cine, 102:266-269, 1985, and is reproduced here with permission. Sources American College of Physicians. 1983a. Fact Sheet: Clinical Efficacy Assessment Project (CEAP). Phila- delphia. American College of Physicians. 1983b. Clinical Efficacy Assessment Project Procedural Manual. Phil- adelphia. American College of Physicians. 1983c. Clinical Efficacy Assessment Project Final Report. December 31. Philadelphia. Ball, J. R., and L. J. White. American College of Physicians. 1985. Personal communications. Health and Public Policy Committee, American College of Physicians. 1985. Endoscopy in the Evalua- tion of Dyspepsia. Annals of Internal Medicine 102:266-269.

282 ASSESSING MEDICAL TECHNOLOGY Reprinted from ANNALS OF INTERNAL MEDICINE Vol. 102; No. 2 February 1985 Reprinted in USA Endoscopy in the Evaluation of Dyspepsia HEALTH AND PUBLIC POLICY COMMITTEE,* AMERICAN COLLEGE OF PHYSICIANS; Philadelphia, Pennsylvania DYSPEPSIA, frequently seen in the general population by primary care physicians and gastroenterologists, has been a common indication for esophagogastroduodenoscopy. Any recommendations regarding the use of this tech- nique in patients with dyspepsia depend on a precise defi- nition of the symptom. The term "dyspepsia," however, represents a vague grouping of upper abdominal symp- toms that may be manifested by various underlying ill- nesses and pathophysiologic findings. The basic element of dyspepsia is epigastric pain or discomfort, accompa- nied by fullness, burning, belching, bloating, nausea, vomiting, fatty food intolerance, or difficulty completing a meal; bowel habits generally remain unaltered. Despite the difficulties in precisely defining dyspepsia, most stud- ies agree that the pathologic finding common in dyspeptic patients may be classified as either gastric ulcer, duodenal ulcer, gastric cancer, or non-ulcer non-cancer dyspepsia ( 1 - 1 5 ). Heartburn, a hot or burning sensation located in the substernal region, is often related to position and is gen- erally distinguishable from dyspepsia by researchers, clinicians, and patients. The symptoms of biliary colic, visceral pain characterized by a severe, steady ache, are usually distinguishable from the epigastric discomfort identified as dyspepsia. In fact, cholecystitis has been in- cluded as a cause of dyspepsia in only a few studies, usu- ally in referred patients. Because the literature and the clinical research describing the evaluation of heartburn and biliary colic are generally distinct from that describ- ing dyspepsia, they will not be considered in this review. This statement addresses the clinical efficacy of esopha- gogastroduodenoscopy in the evaluation of patients with dyspepsia as an isolated symptom. These patients will be distinguished from patients who have dyspepsia in addi- tion to weight loss, severe systemic illness, obstruction, perforation, or multisystem disease. Esophagogastroduodenoscopy is a diagnostic tech- nique that offers clinical information regarding the patient's gastrointestinal symptoms by allowing visual in- spection of the mucosal surfaces of the esophagus, stom- *This paper was authored by Katherine Kahn,,M.D., and Sheldon Green- field, M.D., and was developed for the Health and Public Policy Committee by the Clinical Efficacy Assessment Subcommittee: Donald E. Olson, M.D., Chairman; David Banta, M.D.; Howard S. Frazier, M.D., Richard B. Hor- nick, M.D.; Seymour Perry, M.D.; and Willis C. Maddrey, M.D. Members of the Health and Public Policy Committee for the 1984-85 term include Edwin P. Maynard III, M.D., Chairman; John H. Eisenberg, M.D., Richard G. Farmer, M.D.; Daniel D. Federman, M.D.; John R. Hogness, M.D., Leo E. Hollister, M.D.; Charles E. Lewis, M.D.; Donald E. Olson, M.D., Mal- colm L. Peterson, M.D.; Theodore B. Schwartz, M.D., and Helen L. Smits, M.D. This paper was adopted by The Executive Committee of the Board of Regents on 16 November 1984. 266 Annals of Internal Medicine. 1985;102:266-269. ach, and duodenum. Most fiberoptic endoscopes are ap- proximately 1 metre in length, have a visual field width of 85 to 105 deg. and a shaft that contains channels for passage of biopsy forceps, cytology brushes, and washing or suction catheters (16, 17). The technique generally requires 15 to 30 minutes, including the time for premed- icating the patient (18, 19). The examination may be done in the hospital, ambulatory clinic, or physician's office. Safety Upper gastrointestinal endoscopy has a small but defi- nite risk of complications. Any estimate of the complica- tion rate in a patient with dyspepsia is limited, because indications for endoscopy are only rarely mentioned in reports. A 1974 survey by the American Society for Gas- trointestinal Endoscopy of 21 1 410 procedures showed an overall complication rate of 0.13% (20). The major com- plications were perforation (0.03~o), bleeding (0.03%), cardiopulmonary problems (0.06% ), and infection (0.008%). It seems reasonable to assume that the al- ready low complication rate for esophagogastroduode- noscopy in general is even lower when considering the rate of complication in the dyspeptic patient who will usually be less sick than the patient with gastrointestinal bleeding. Costs Standard texts of gastroenterology, as well as the American Society for Gastrointestinal Endoscopy, have ascribed to financial considerations the usual sequence of an upper gastrointestinal barium study preceding eso- phagogastroduodenoscopy in the evaluation of the dys- peptic patient (21-23). However, the advent of newer endoscopes, the training of more endoscopists, the reduc- tion in the time to do a complete esophagogastroendo- scopic examination, in conjunction with the high predic- tive value of this technique, have led some to suggest a need to reevaluate its costs. Although not generally men- tioned, other costs must also be considered (18). When endoscopy is done in a hospital rather than a physician's office, a hospital room fee is also charged. Charges sub- mitted for diagnostic esophagogastroduadenoscopy by in- dividual physicians in 1983 for Medicare patients in six geographic regions averaged $325 with a range from $145 to $900. The initial cost of an endoscope and light source ranges from $10000 to $20000. The charges for upper gastrointestinal series generally do not exceed $150 in- cluding both physician and procedure charges. The cost ¢:)19~35 American College of Physicians

APPENDIX A: PROFILES of medical therapy with either liquid antacids, cimeti- dine, or both, ranges from $35 to $60 per month (24). Efficacy Evaluation of the efficacy of esophagogastroduodenos- copy depends on the prevalence of the disease conditions underlying the symptom, the cost and effectiveness of di- agnostic modalities, and the effect this technique will have on patient outcome. Diagnostic options include pre- scribing an immediate upper gastrointestinal barium se- ries, immediate esophagogastroduodenoscopy, or empiric treatment with a subsequent diagnostic investigation. Most reports have described the diagnostic sequence of upper gastrointestinal barium series for patients with dys- pepsia followed by esophagogastroduodenoscopy for sus- picious lesions (1, 21, 22).This strategy is based on the perceived need for early diagnosis and the low cost of upper gastrointestinal series compared to that of eso- phagogastroduodenoscopy. In order to further conserve costs while maintaining benefits, alternative strategies must be considered. One strategy is to treat empirically all patients with dyspepsia who do not have clinically obvious serious disease by withdrawing offending agents (ethyl alcohol, ulcerogenic medications, and cigarettes) and by prescribing antacids or H2 blockers. Patients with clinically obvious serious conditions such as weight loss, severe systemic illness, bleeding, perforation, symptoms of upper gastrointestinal obstruction, or other evidence for cancer should have prompt diagnostic investigation. The following five reasons support the initial use of clinical appraisal followed by response to an empiric course of therapy in patients with uncomplicated dyspep- sia. Esophagogastroduodenoscopy would be reserved for patients who remain symptomatic or have a relapse. First, only 20% of patients with dyspepsia have an ulcer disease: either duodenal ulcer (range, 7% to 34%), or gastric ulcer (range, 2% to 20%) (1-15). Fewer than 1% of patients with dyspepsia will have cancer (2, 4, 5, 11, 12). The prevalence of gastritis, duodenitis, or ero- sions (non-ulcer dyspepsia) is difficult to quantify, but the range reported in the literature is from 5% to 40%. The remainder of patients have dyspepsia without appar- ent pathologic characteristics despite endoscopic or ra- diographic evaluation. These estimates for specific disease entities may be high because information about the prev- alence of associated diseases is closely linked to the set- ting in which the information was obtained (5, 12). In fact, the changing practices of some segments of the American population toward visiting the physician after a shorter duration of symptoms may dramatically lower the prevalence rates of dyspepsia-associated diseases (25). Although esophagogastroduodenoscopy as an ini- tial diagnostic approach might offer additional diagnostic information, the marginal value of such information must be assessed. Initial therapy for patients with dyspepsia as an isolated symptom remains the same whether the diag- nosis is duodenal ulcer, gastric ulcer, gastroduodenitis, or even normal mucosa. Although a visual image of the gas- trointestinal mucosa allows a more precise diagnosis, the 283 value of such information is minimal if it does not change patient management or outcome. Second, if gastric cancer occurred frequently, for ex- ample, in greater than 5% of patients with dyspepsia, endoscopic diagnosis in all dyspeptic patients might be appropriate. However, in primary care practice the prev- alence will be lower, probably less than 1%. No physi- cian wants to overlook a case of highly curable cancer. But in this country, the detection rate of early gastric cancer has not increased to more than approximately 6% of those stomach cancers found (26-32). Using a preva- lence of 1% of dyspeptic patients having cancer, and 6% of those cancer patients having early gastric cancer, 6 per 10 000 dyspeptic patients will have early gastric cancer. Although the 5-year survival rate for gastric cancer de- tected early is 95%, the infrequency of early detection leaves the overall 5-year survival for gastric cancer in this country at 10% with an occasional 5-year survival rate at 30% (33). It is not known precisely how many of the patients with potentially curable early gastric cancer will progress to higher, less curable stages if esophagogastro- duodenoscopy is delayed 6 to 8 weeks in favor of empiric treatment, but there is no evidence to suggest that it is more than a few. It is difficult to justify performing im- mediate esophagogastroduodenoscopy or upper gastroin- testinal series on all patients with dyspepsia in the expec- tation of curing cancer. Third, the history of treated ulcer disease must be con- sidered. Fifteen percent of patients with gastric ulcer will have a persistent ulcer crater after 8 weeks of therapy despite having complete resolution of symptoms (34). Of these asymptomatic patients with persistent gastric ulcer, it is safe to assume that most will heal even without ther- apy, because the healing rate for patients with gastric ulcers treated with placebo is up to 68% at 12 weeks. For patients who become asymptomatic while being treated, many will have recurrence of symptoms after therapy is discontinued and at that time may receive esophagogas- troduodenoscopy. Of patients whose gastric ulcer re- quires more than 9 weeks to heal, between 55% and 89% may have a recurrent ulcer within the year (35-37). Many of these patients would then be endoscopically ex- amined for symptom recurrence. The same is true for patients with duodenal ulcer in whom approximately 50% to 85% recur within the year (38). Virtually all patients with refractory ulcers will be identified by the recurrence of symptoms after therapy is withdrawn. There is no evidence that the complication rate among patients treated initially with empiric therapy and endo- scopically examined later for recurrent or persistent symptoms should be any higher than in those patients diagnosed initially by esophagogastroduodenoscopy. Fourth, approximately 70% of patients with gastric (or duodenal) ulcer or mucosal disease will become asymptomatic within several weeks after institution of therapy (34, 38). In the absence of symptom recurrence, they will require no further diagnostic evaluation. In ad- dition, patients who have symptom recurrence after ther- apy will require further diagnostic evaluation. Position Paper 267

284 Fifth, the effect of an empiric trial of therapy on pa- tients who do not have an ulcer or gastroduodenitis must be considered. Studies have shown that some patients with normal findings on radiography and endoscopy have histologic evidence for acute or chronic gastroduodenitis (3941). Some fraction of patients with dyspeptic symp- toms, who do not have peptic disease by any criteria, will have symptom resolution with empiric treatment. Limit- ing the treatment period to 6 to 8 weeks will avoid chron- ic usage of unnecessary medication. The persistence of symptoms despite 6 to 8 weeks of therapy or the exacer- bation of symptoms during therapy, must result in fur- ther diagnostic evaluation. Use of the proposed strategy would provide empiric therapy as the initial approach to patients with dyspepsia as an isolated symptom. Endoscopy-will be reserved for two subsets of patients: those who have no or minimal response to therapy after 7 to 10 days; and the approxi- mately 30% of patients whose symptoms persist, im- proved but not resolved, after a 6- to 8-week period. If all dyspeptic patients are treated empincally, considerable diagnostic resources will be saved. After selecting this group of patients with refractory symptoms, the question must be asked whether the usual pattern of upper gastrointestinal series tests followed by esophagogastroduodenoscopy is still the appropriate se- quence. It can be argued that the higher false-negative rate of greater than 18% and the false-positive rate of between 13% and 35% for the upper gastrointestinal se- r~es is unacceptable for this small group of patients who are refractory to treatment or at higher risk of cancer (42-56). Further, the use of double contrast reduces the false-negative rate only to between 9% and 17% and the false-positive rate to between 8% and 11% (46, 51, 53, 54). In addition, barium studies do not allow the oppor- tunity for biopsy or cytologic examination that is indicat- ed in patients with radiographic lesions considered to be suspicious. To detect cancer or to decide on long-term or modified therapy, the more accurate diagnostic modality of esophagogastroduodenoscopy is preferable. Recommendation Considenng the available data on costs and benefits, as well as the relationships between diagnoses, treatments, and patient outcomes, it seems prudent to adopt strate- g~es that reduce financial costs, yet retain the potential for appropriate patient management. Reserving the use of diagnostic esophagogastroduodenoscopy for those pa- tients with symptoms despite 6 to 8 weeks of therapy provides a strategy for cost reduction while maintaining prudent patient care. Those patients who have no re- sponse to therapy after 7 to 10 days, those who develop complications of peptic disease, those who show signs of a severe systemic illness, and those with symptom recur- rence should receive diagnostic evaluation earlier in the course of their illness. Adoption of this recommendation must be modified in the light of each patient's clinical presentation, including patients at high risk or with mul- tisystem problems. 268 February ]9f95 · Annals of Internal Meclicine · Vo/`Jme 102 ~ Number2 ASSESSING MEDICAL TECHNOLOGY ACKNOWLEDGMENTS: The Clinical Efficacy Assessment Project (CEAP) of the American College of Physicians is designed to evaluate and inform College members and others about the safety and efficacy of diagnos- tic and therapeutic modalities. Evaluation of technologies begins with a no- tice in Annals of Internal Medicine and the ACP Observer inviting com- ments. Appropriate members of the Council of Medical Societies and the Council of Subspecialty Societies as well as other experts are asked to review technologies. The CEAP statements thus represent a synthesis of the litera- ture and expert opinion and are intended to reflect the current state-of-the- art knowledge concerning a technology. Statements may be reconsidered as new information becomes available. Grant support: The development of this paper by the Clinical Efficacy Assessment Project was funded by the John A. Hartford Foundation. · Requests for reprints should be addressed to Linda Johnson White, Clirri- cal Efficacy Assessment Project, Department of Health and Public Policy, American College of Physicians, 4200 Pine Street; Philadelphia, PA 19104. References 1. Data base on dyspepsia [ Editorial ] . Br Mcd J. 1978;6121:1 1634. 2. MOLLMANN KM, BONNEVIE O. GUDBRAND MOYER E, WULFF HR. A diagnostic study of patients with upper abdominal pain. Scand J Gas- trocnterol. 1975;10:105-9. 3. BARNES RJ, GEAR MWL, N~coL A, DEW AB. Study of dyspepsia in a general practice as assessed by endoscopy and radiology. Br Mcd J. 1974;4:214-6. ,. KI]L J. ANDERSON D. X-ray examination and/or endoscopy in the diag- nosis of gastroduodenal ulcer and cancer. Scand J G~strocntcrol. 1979;15:3943. 5. READ L, PASS TM, KOMAROFF AL. Diagnosis and treatment of dys- pepsia, a cost effectiveness analysis. Mcd Delis Making. 1982,2:416-38. 6. HORROCKS JC, DE DOMBAL FT. Clinical presentation of patients with dyspepsia, detailed symptomatic study of 360 patients. Gut. 1978;19:19- 26. 7. RINALDO JA JR, SCHE~NOIC P. RUPE CE. Symptoms diagnosis: a math- ematical analysis of epigastric pain. Ann Intern Mcd. 1963;59:145-54. 8. Ross P. Dt'TToN AM. Computer analysis of symptom complexes in patients having upper gastrointestinal examinations. Dig Dis Sci. 1972;17:248-54. 9. SCHEINOIC PA, RINALDO JA JR. Symptom diagnosis: optimal subsets for upper abdominal pain. Comput Biomcd Rcs. 1967;1:221-36. 10. COLcHER H. Current concepts, gastrointestinal endoscopy. N Engl J Mcd. 1975;293:1129-3 1. 11. MARTON KI, Sox HC, WASSON J. DUISENBERG CE. The clinical value of the upper gastrointestinal tract roentgenogram series. Arch Intern Mcd. 1980;140:191-5. 12. MEAD GM, MORRIS A, WEBSTER GK, LANGMAN MJS. Uses of bari- um meal examination in dyspeptic patients under 50. Br Mad J. 1977;1:1460-1. 13. LIEBLING PO. The use and abuse of barium meals. Practitioner. 1 966; 196:695-702. 14. GEAR MWL, BARNES RJ. Endoscopic studies of dyspepsia in a general practice. Br Med J. 1980;280:1 136-7. 15. F'sHER JA, SuRR'wE JO, VARTAN CP, LOEHRY CA. Upper gastroin- testinal endoscopy—a GP service. Br Mcd J. 1977;2:1199-1201. 16. VENNES JA, S'LVERsTE~N FE. UGI fiberoptic endoscopy. In: SLe~seN- GER MH, FORDTRAN JS, eds. Gastrointestinal Disease. Philadelphia: W.B. Saunders; 1983:1599-1615. 17. H'RscHow'tz BI. Endoscopic examination of the stomach and duode- nal cap with the fiberscope. Lanect. 1961;1:1074. 18. SHOWsTAclC JA, SCHROEDER SA, STEINBERG HR. Evaluating the costs and benefits of a diagnostic technology. Mcd Care. 1981;19:498-509. 19. TEDESCO FJ, GRIFFIN JW, CR~sP WL, ANTHONY HF JR. Skinny upper gastrointestinal endoscopy—the initial diagnostic tool: a prospective comparison of upper gastrointestinal endoscopy and radiology. J Olin Gastrocntcrol. 1980;2:27-30. 20. S~Lv~s SE, NEBEL O. ROGERS G. Endoscopic complications: results of the 1974 American Society for Gastroenterology Survey. JAMA. 1 976;235:928-30. 21. AMERICAN SOc~ETY FOR GASTROINTESTINAL ENDOSCOPY. The Role of Endoscopy in the Management of Patients with Duodenal Dis~sc, Guidelines for Clinical Application. The Standards of Training and Practice Committee. American Society for Gastrointestinal Endoscopy; 1978. 22. RICHARDSON CT. Gastric ulcer. Gastrointestinal Disease. In: SLEISEN_ GER MH, FORDTRAN JS, eds. Philadelphia: W.B. Saunders; 1983:672- 93. 23. SPIRO H. Clinical Gastrocntcrology. New York: Macmillan Publishing Co., Inc; 1983:304-54. 24. The Rcdbook Drug Topic. Oradell, New Jersey: Medical Economics Co., Inc.; 1984:68, 311. 25. NEWHOUSE J. MANNING W. MORRIS C, et al. Some interim results

APPENDIX A: PROFILES from a controlled trial of cost sharing in health insurance. N Engl J Mcd. 1981;30S:1501-7. 26. CADY B. RAMDSEN D, STEIN A, HAGGITT RC. Gastric cancer: con- temporary aspects. Am JSurg. 1977;133:423-9. 27. MORRISSEY JF. The diagnosis of early gastric cancer: a survey of experi- ence in the United States. Gastrointest Endoscopy. 1976;23:13-5. 28. ADASHEK K, SANDER J. LONGMIRE WP. Cancer of the stomach: review of consecutive ten year intervals. Ann Surg. 1979;189:6-10. 29. DUPONT JB, RILLENS LEE J. BURTON OR, COHN I JR: Adenocarcino- ma of the stomach: review of 1,497 cases. Cancer. 1978;41:941-7. 30. OLEARCHYK AS. Gastric carcinoma: a critical review of 243 cases. Am J Gastrocntcrol. 1978;70:2545. 31. EVANS DMD, CRAVEN JL, MURPHY F. CLEARY BK. Comparison of early gastric cancer in Britain and Japan. Gut. 1978;19:1-9. 32. SUGAWA C, SCHUMAN BM. Primer of Gastrointestinal Fiberoptic En- doscopy. Boston: Little Brown & Co; 1981. 33. K^SUAG] T; KOBAYASH! S. Evaluation of biopsy and cytology in the diagnosis of gastric cancer. Am J Gastrocntcrol. 1974;62:199. 34. ISENBERG JI, PETERSON WL, ELASHOFF JD, et al. Healing of benign gastric ulcer with low-dose antacid or cimetidine: a double-blind ran- domized placebo-controlled trial. NEnglJMcd. 1983;308:1319-24. 35. PIPE DW, SHINNERS J. GRE!G M, THOMAS J. WALLER SL. Effect of ulcer healing on the prognosis of chronic gastric ulcer. Gut. 1978;19:419-24. 36. JENSEN KB, MOLLMANN KM, RAHBEK I, MADSEN JR, RUNE SJ, WULFF HR. Prophylactic effect of cimetidine in gastric ulcer patients. Stand J Gastroentcrol. 1979;14:175-6. 37. MACHELL RJ, C~cL~T'RA PJ, FARTHING MJG, Dick AP, HUNTER JO. Cimetidine in the prevention of gastric ulcer relapse. Postgrad Med J. 1979;SS:393-5. 38. IPPoLm AF, STURDEVANT RA, ISENBERG JI, et al. Cimetidine versus intensive antacid therapy for duodenal ulcer. Gastrocntcrology. 1978;74:393-5. 39. GREsN~Aw R. SHEAHAN DC, DELucA VA, MILLER D, MYERSON D, MYERSON P. Gastroduodeniti~ a broader concept of peptic ulcer dis- ease. Dig Dis Sci. 1980;25:66~72. 40. DELucA VA, WINNAN G. SHEAHAN DC, et al. Is gastroduodenitis part of the spectrum of peptic ulcer disease? J Clin Gastrocntcrol. 1981;3:17- 22. 41. LAGARDE S. SPIRO H. Non-ulcer dyspepsia. Clin Gastrocntcrol. 285 46. 48. 1 984;13:43746. WAYE JD. The current state of esophagoscopy, gastroscopy, and duode- noscopy. Mt Sinai J Mad. 1975;42:57-80. KNUTSON CO, MAX MH, AHMAD W. POLK HC JR. Should flexible fiberoptic endoscopy replace barium contrast study of the upper gastro- intestinal tract? Surgery. 1978;84:609-15. 44. MARTIN TR, VENNES JA, S~Lv~s SE, ANSEL HJ. A comparison of upper gastrointestinal endoscopy and radiography. J Clin Gastrocntcrol. 1980;2:21-5. 45. MARTIN TR, VENNES JA, S~Lv~s SE, ANSEL HJ. UGI endoscopy vs. radiography: is radiography obsolete? J Clin Gastrocntcrol. 1980;2:27- 30. MONTAGNE J. Moss AA, MARouLls AR. Double-blind study of single and double contrast upper gastrointestinal examinations using endosco- py as a control. Am JRoentgenol. 1978;130:1041-5. 47. TEDESCO FJ, BEST WR, LITTMAN A, et al. Role of gastroscopy in gastric ulcer patients: planning a prospective study. Gastroentcrology. 1977;73:170-3. WEINSTEIN WM. Gastroscopy for gastric ulcer. Gastroentcrology. 1977;73:1 160-2. 49. CUMBERLAND DC. Fibre-optic endoscopy and radiology in the investi- gation of the upper gastrointestinal tract. Clin Radiol. 1975;26:223-36. 50. DEKKER W. TYTGAT ON. Diagnostic accuracy of fiber-endoscopy in the detection of upper intestinal malignancy, a follow-up analysis. Gas- troenterology. 1977;73:7 10-4. 51. HERLINGER H. GLANv'LLE JN, KREEL L. An evaluation of the double contrast barium meal (DCBM) against endoscopy. Or Med J. 1977;28:307-14. 52. LAUFER I, MULLENS JE, HAM~L1oN J. The diagnostic accuracy of barium studies of the stomach and duodenum—correlation with endos- copy. Radiology. 1975;115:569-73. 53. LAUFER I. Assessment of the accuracy of double contrast gastroduode- nal radiology. Gastroentcrology. 1976;71:87~8. 54. ROGERS IM, SOICH] GS, MOULE B. JOFFE SN, BLUMGART LH. Endos- copy and routine and double~ontrast barium meal in diagnosis of gas- tric and duodenal disorders. Lancet. 1976;1:901-2. 55. SALTER RH. Upper-gastrointestinal endoscopy in perspective. Lancet. 1975;2:863-4. 56. SCHUMAN BM. The gastroscopic yield from the negative upper gastroin- testinal series. Gastrocnterol Endosc. 1972;19:79-82. Position Paper 2 69

Hospital Technology Series Program American Hospital Association Division of Technology Management and Policy 840 North Shore Drive Chicago, ILL 60611 (312) 280 6026 Major Emphases of Technology Assessment Activities Concerns Technology Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X X X X Ethical/Legal/ Social Drugs Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/ Administrative Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded A pplicat~on of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods X Cost analyses Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $250,000 AMERICAN HOSPITAL ASSOCIATION HOSPITAL TECHNOLOGY SERIES PROGRAM Introduction The American Hospital Association (AMA) initiated the Hospital Technology Series pro- gram in 1982. This program is a health care technology evaluation and information dis- semination program targeted to the hospital administrator. It is coordinated by the AHA Division of Technology Management and Policy. The Hospital Technology Series pro- vides three publications (described below un- der Reporting), including Guideline Reports, which features AHA technology evaluations. 286 Purpose The primary purpose of the AHA Hospital Technology Series program is to assist hospi- tal administrators in making prudent and informed management and investment deci- sions regarding new and existing technolo- gies. Subjects of Assessment The Hospital Technology Series program evaluates diagnostic, therapeutic, and sup- port systems and technologies. The program deals primarily with service implications of technological advances from the hospital's perspective. The program generally does not

APPENDIX A: PROFILES evaluate procedures, although they are dis- cussed insofar as they bear upon strategic Process equipment and service choices. Stage of Diffusion The program is concerned with new and existing technologies. Concerns AHA evaluations are primarily concerned with the cost and service implications of tech- nologies that are entering clinical practice. They also consider manufacturer issues, such as vendor stability, the capacity for technolo- gies to be upgraded, and other compared at- tributes of competing technologies. Evalua- tions published in Guideline Reports emphasize what to look for in acquiring and managing technologies. Although evalua- tions do not include brand name ratings, they sometimes provide brand-specific informa- tion on commercially available equipment, such as cost and installation information, ser- vice support arrangements, etc. Specifically, AHA evaluations are most concerned with the following: 1. cost and organizational implications; 2. installation costs; 3. staffing and training requirements; 4. probable number of patients affected; 5. effects on other hospital resources, e. g., the extent to which a technology will enable the replacement of existing resources, or the extent to which it will necessitate the addi- tion of new resources; and 6. clinical effectiveness: not patient out- comes per se, but effects on the use of hospital resources, such as inpatient versus outpatient stay, average length of stay, etc. Requests Topics originate with program staff. Selection Subjects for assessment are selected on the basis of a staff review of their importance to hospital management, especially their im- pact on costs. 287 The evaluations are syntheses of the litera- ture, focused interviews with manufacturers and users, and compilations of reported user- based experience in such matters as negotiat- ing purchase contracts, common mistakes made in implementation, etc. Outside con- sultants are frequently used in these evalua- tions. Assessors Evaluations are conducted by staff of the AHA Division of Technology Management and Policy, with the assistance of outside consultants. Turnaround Evaluations generally require about 6 months from the time of selection to the fin- ished report. Reporting Evaluation findings are reported in Guide- line Reports issued as the evaluations are completed. This is one of three publications of the AHA Hospital Technology Series, which includes the following: · Guideline Reports: evaluations of spe- cific hospital technologies; approximately eight distributed per year to member hospi- tals. By 1984, AHA had completed approxi- mately 20 guideline reports. · Executive Briefing: an overview of ma- jor developments affecting hospitals' use of technology in the delivery of patient care. Di- rected to hospital chief executive officers (CEOs); distributed monthly. · Technology Scanner: a collection of cat- egorized summaries of articles relevant to hospital technology, drawn from 70 medical and technical journals. Directed to hospital administrators; distributed monthly. Guideline Reports include annual com- pilations of the technology assessments con- ducted by the Office of Health Technology Assessment of the Public Health Service for the Health Care Financing Administration

288 (HCFA) to assist HCFA in making Medicare coverage decisions. A listing of Guideline Re- poTts issued by AHA is shown in Table A-2. Selected Guideline Reports and other pro- gram reports are summarized in Hospitals magazine. TABLE A-2 Guideline Reports Issued by the AHA Hospital Technology Series, 1982-1985 Diagnostic Systems and Technologies Nuclear Magnetic Resonance (NMR) Computerized Tomographic Scanners Digital Subtraction Angiography Echocardiography Computerized Arrhythmia Monitoring Systems Automated Indirect Blood Pressure Measurement De- vices Trends in Nuclear Medicine NMR—Issues for 1985 and Beyond Therapeutic Systems and Technologies Evaluation Methods for Intensive Care Unit Systems Automated Infusion Devices Autotransfusion Units Adult Volume Ventilators Lithotripters Computer Technologies Clinical Laboratory Information Systems Materials Management Information Systems Microcomputers in Hospitals Other Technology-Related Reports Medicare Technology Assessments: 1981 Medicare Technology Assessments: 1982 Medicare Technology Assessments: 1983 Ethylene Oxide Sterilization Buying and Selling Used Medical Equipment Purchasing a Satellite Receiving Earth Terminal Equipment Acquisition Under Prospective Payment A Medical Device Recall and Reporting System Bar Code Technology—Applications in Health Care ASSESSING MEDICAL TECHNOLOGY The AHA Hospital Technology Series, in- cluding Guideline Reports, is available at a yearly subscription cost of $150; individual issues of Guideline Reports can also be or- dered separately at a nominal fee. Impact Approximately 1,250 U. S. hospitals sub- scribe to the Hospital Technology Series. Reassessment Technologies will be reassessed subject to perceived need of hospitals and new informa- tion. Reassessments will follow the same for- mat as the original assessments. Funding/Budget The annual budget of the Hospital Tech- nology Series program is approximately $250,000. Program support is derived from subscription fees. Example On the following pages is a technology briefing excerpted by AHA from its February 1985 Guideline Report "NMR- Issues for 1985 and Beyond." The full 235-page report is available from AHA. Sources American Hospital Association. 1983. Hospital Technology Series (pamphlet). Chicago. American Hospital Association. 1985. AHA Hospi- tal Technology Series Guideline Report: NMR—Is- sues for 1985 and Beyond (technology briefing ex- cerpt). Chicago. Goodhart, M., Manager, Technology Policy, American Hospital Association. 1985. Personal com- munications.

APPENDIX A: PROFILES NUCLEAR MAGNETIC RESONANCE A technology briefing excerpted from NMR--Issues for 1985 and Beyond, a Hospital Technology Series guideline report. 289 Nuclear magnetic resonance, (NMR) is a diagnostic imaging modality that uses magnetic and radio-frequency fields to image body tissue and monitor body chemistry non-invasively. It uses no ionizing radiation or contrast agents, and is unimpeded by bone. Because it is so highly sensitive and safe, it is becoming a replacement for some CT as well as an array of invasive, often risky procedures such as myelography and angiography. Yet the rate of diffusion of this technology may not be proportional to its clinical superiority because NMR is reaching the health care marketplace at a time when the economic climate is volatile. The hospital that purchases prematurely without carefully weighing the options, risks, and benefits associated with NMR could find itself in severe financial difficulties. At the same time the hospital that fails to provide access to the modality could find itself at a considerable competitive disadvantage, particularly if neurology, cardiology, and/or oncology account for a substantial percentage of admissions. Once today's better educated, better informed health care consumers, and their referring physicians truly understand the technology and the advantages it can offer in terms of cost avoidance and reduced patient risk and suffering, they are likely to demand NMR services and seek them elsewhere if the hospital can't provide them. Conversely, the hospital that competes in these areas and does offer NMR could enjoy a competitive edge. Because of the recent wide availability of mobile systems NMR has become an important issue for smaller hospitals as well as larger ones. These and other factors make the decision to invest in NMR a difficult one. Determining the need for NMR Some clinical applications save money By eliminating the need for many other exams, biopsies, and exploratory surgical procedures, NMR could eventually save health care dollars and substantially reduce risk and discomfort to the patient. For example, today contrast enhanced CT and myelograms are used to diagnose tumors in the posterior fossa of the brain or on the spinal column. Abdominal aortic aneurysms often require angiography. Examining the prostate gland to determine the cause of an enlargement usually requires biopsy or exploratory surgery. NMR has already demonstrated its ability to minimize the need for some of these procedures or to displace them entirely as well as to shorten the hospital stay usually associated with them. AHA has identified some 40 cost saving applications, 19 of which are essentially here now and would clearly save money if employed. Based on clinical experience with only 7 of the 19 currently available cost saving applications, we estimate (we believe conservatively) that NMR should eliminate at least 20% of CT head, 7.5% of body, 28% of major vessel angiography, and 50% of kidney angiography. We also believe that targeting

290 ASSESSING MEDICAL TECHNOLOGY research efforts intensively in these specific areas could do much to encouage more universal reimbursement. Projecting utilization Key to assuring that your financial projections are accurate, and to securing CON approval, is a reliable utilization projection. Seven methodologies are currently in use, the most popular of which was developed by NMR Inc., a joint venture of three community hospitals in Omaha. It scores the percentage of patients for whom NMR would be indicated in each of over 250 ICD-9-CM categories. To project utilization for any individual hospital or group of hospitals, the number of patients discharged in each category can be multiplied by the percentage figure for that category, and the total of all categories computed. Factors that may distort your projections A number of planners have argued that this and other similar methodologies now in use are inherently conservative for several reasons. First of all, they are based on inpatient data, even though most of the NMR exams will probably be performed on outpatients. This is misleading, however, because many of those who are screened for serious conditions by NMR on an outpatient basis, and who may even be treated in ambulatory surgery facilities or receive radiation therapy on an outpatient basis, are eventually treated as inpatients. Only primary diagnoses are used to calculate percentages even though secondary diagnoses could also trigger use of NMR; only one NMR scan per patient is assumed when scans may be multiple, especially for cancer patients; and only current clinical applications are used to calculate the patient base. Two additional factors could lead to inaccurate projections. Although the radiologists who determined the weighting percentages obviously have some knowledge of NMR's progress from attending professional meetings and reading the literature, few, if any, have had direct clinical experience with NMR. This could lead them to embrace more or fewer applications than would radiologists who have direct experience. Also the degree of superiority of NMR to various other less expensive tests has yet to be fully explored. In many cases a sophisticated, and expensive modality such as NMR may not be needed, and if so, NMR should not be substituted for the lower cost technique, even if that technique is somewhat cruder. Thus listing NMR as appropriate for treating certain disease categories when lower-cost options already exist could result in counting duplicative tests that will eventually be eliminated, and which for the moment would only serve to inflate the percentages. To respond to these and other issues raised, AHA developed its own model. We subjected 321 ICD-9-CM categories to a panel of NMR experts, each of whom has had access to an NMR unit for a couple of years, and some of whom are published authorities in the field of NMR. We solicited an independent judgment from each panelist as to the percentage of NMR use in each of the ICD-9-CM categories. That disagreement as to what constitutes accepted use for NMR surfaced is hardly surprising. We eliminated those categories where disagreement was substantial.

APPENDIX A: PROFILES 291 The result is a conservative model for projecting utilization based on current clinical applications. Using this model, we forecast 1.8 million patients annually would need scans. When followup procedures on these patients are added the total number of scans becomes 2.9 million annually. Followup procedures were calculated by using an accepted methodology for computing followup procedures for CT. By interfacing our NMR model with the CT model, we estimated that overall NMR will replace 34% of CT. The greatest area of impact on CT is projected to be in the area of nervous system disease (94% replacement), circulatory system disease (75% replacement) and neoplasms (30% replacement). Selecting the magnet High field strength or low field strength - which is best? No issue is more hotly debated than that of the relative superiority of high field strength to low field strength systems. Unfortunately, the heat of this debate has exaggerated the differences. In most NMR applications, the hydrogen atom is resonated to produce the images. This is called proton-imaging and it can be performed at high or low field strengths. The difference (if it exists at all) between proton images produced at high field strengths and those produced at low field strengths, in terms of throughput or quality, appears to be small. The debate obscures the basic difference between high and low field strength systems which is that only high field strength systems will be useful for non-proton imaging applications (where atoms other than hydrogen atoms are resonated to produce the image) and spectroscopy. As far as proton imaging is concerned, the better low field systems always seem to be able to match and, in some cases and for certain applications, exceed the performance capabilities of the higher field strength systems, producing very high quality images within reasonable time frames. We predict most of the improvements that will come in proton imaging will probably be due to improvements in coil technology (particularly surface coils) and not to increases in the strength of the magnetic field. The significant contribution of high field strength is likely to be in spectroscopy applications. The future of spectroscopy Spectroscopy is a non-invasive technique for measuring biochemical changes in tissue that signal the onset of disease long before other symptoms appear. If it succeeds, it could eventually replace invasive biopsy. Spectroscopy, however, is still very much in the experimental stage. It is possible only on the higher field strength systems, and is often cited as a reason for purchasing a higher field strength system. We contend that potential purchasers should not tell themselves that Thigh field strength will allow us to do spectroscopy, but rather ask the question What kind of spectroscopy will be possible with the 1.5T or 2T units available today, and what can we use it for?. A number of recent developments show that the 1.5T to 2T systems can produce phosphorus spectra that yield some useful information. However, the high resolution phosphorus spectra of small, well localized tissue masses that physicians predict will be useful have not yet been produced on current

292 ASSESSING MEDICAL TECHNOLOGY high field strength systems. Some researchers think this kind of spectra can be generated at 1. 5T; others believe it possible only at much higher field strengths of 4T or 8T. It will be a few years before the clinical significance of spectroscopy can be determined. Because the field strength debate is far from being resolved, we conclude that the decision to purchase a higher field strength system should be based on careful monitoring and assessment of whether or not high resolution spectra of small, well localized tissue masses can eventually be produced at fields of 1. 5T to 2T. Current high field strength systems cost nearly twice as much as the lower field strength systems when the additional architectural costs are included, and the number of applications of low field strength systems is already large. The progress of reimbursement Much of the optimism about the progress of reimbursement is based on encouraging results of surveys taken of private commercial insurance carriers who are exhibiting a growing willingness to pay. One of these surveys, recently conducted by Mobile Technology Inc., showed that 71% of the top 30 private insurance carriers now pay for NMR services according to company policy guidelines or on a case-by-case basis. This represents an increase of 50% in just four months according to survey researchers. However, most Blue Cross/Blue Shield plans, and HCFA do not yet pay for NMR. If they decide to continue to refuse payment for NMR, or if they establish criteria that are highly specific, the encouraging trend could shift dramatically. Given the wide applicability of NMR technology, and the mounting pressure to contain costs, we find it likely that the reimbursement authorities will be more restrictive and/or indication-specific with respect to NMR than they were with respect to CT. Near term, this is likely to alter projected revenue streams from NMR services. The Hospital Technology Series will continue to monitor developments in the national reimbursement policy for NMR. Staffing Radiologists will need about a year and a half of training in order to fully understand the technology and be able to use it most effectively although some diagnostic skills can be learned in about three months. While NMR images look much like the images produced by CT scanning, the technology that underlies the composition of those images is vastly different. The radiologist unfamiliar with NMR will see structures that look familiar but won't understand why something shows up or fails to show up, and will have to learn how to select a pulse sequence appropriate for detecting the suspected disease. Who will pay for this training looms as a major issue. Introduction of NMR technology can also be expected to raise some turf and staffing issues. These are discussed in a special section of the report to help you better anticipate the length of time you need to allocate for personnel training, and to alert you to political problems you may need to resolve. Choosing Your manufacturer It pays to select both your architect and your manufacturer carefully.

APPENDIX A: PROFILES 293 Manufacturers have varying degrees of expertise in site design and the cost of installing the same magnet can vary as much as $100,000 from one manufacturer to another. Improvements in shielding systems and availability of self-shielding superconducting systems even for the higher field strength units have brought construction costs down. Fifteen manufacturers now produce NMR units, and the number of available magnet types is now eight. An NMR unit can cost from $600,000 to $2.5 million. Some magnet systems are mobile and can be installed in trailers and moved from site to site. These can make the technology available to the smaller institutions on a shared basis, and to institutions in remote locations. In the future, smaller, special purpose, less expensive units for imaging specific areas of the body can be expected. Clinical trials are supposed to begin shortly for one such head-only permanent magnet system, which is expected to sell for only $600,000. With so many options, and so many manufacturers competing for your business you will need to know the strengths and weaknesses of each to decide which one will be most able to support both your present and projected needs. To assist you in choosing an appropriate manufacturer, we have compiled a list of 243 hospital and nonhospital installations of NMR systems worldwide through 1985, by manufacturer. It is published in NMR--Issues for 198S and Beyond, copies of which can be purchased from AHA Services, Inc., 4444 W. Ferdinand, Chicago, IL 60624. The cost is $35 for AHA members; $45 for nonmembers. Quantity discounts are available, and an order form is attached for your convenience.

Diagnostic arid Therapeutic Technology Assessment Program American Medical Association 535 North Dearborn Street Chicago, Illinois 60610 (312) 645 5000 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety . Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X* . X* X Ethical/Legal/ S. 1 ocla1 X* Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X* X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded Application of Technologies Prevention X DiagnosiS/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling Group judgment Xt Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $380,000 * Drugs and medical devices involved in DATTA assessments are addressed in- sofar as they are applied in medical and surgical procedures, e.g., chelation ther- apy or application of implantable infusion pump. Particular brand-name prod- ucts are not compared or assessed as such. t The program polls a panel of experts regarding their rating of a technology, but panel members do not interact as a group in formulating the DATTA opinion. AMERICAN MEDICAL ASSOCIATION DIAGNOSTIC AND THERAPEUTIC TECHNOLOGY ASSESSMENT PROGRAM Introduction The American Medical Association (AMA) is a national organization of 26O,OOO member physicians. The AMA provides technology as- sessment information in several ways. This 294 profile is devoted primarily to the AMA Di- agnostic and Therapeutic Technology Assess- ment Program (DATTA). AMA's primary channel of evaluative in- formation is its 27 scientific publications, es- pecially the Journal of the American Medical Association (lAMA). The AMA also provides assessment information through the reports of the Council on Scientific Affairs. Since its creation in 1976, the council has published

APPENDIX A: PROFILES over 100 reports developed with the assis- tance of staff, often supported by ad hoc ex- pert panels, dealing with advances or contro- versies in diagnostic, therapeutic, and other medical technologies. Many council reports have been published in.lAMA. Since 1979, the Council on Scientific Affairs has issued reports such as the following: · The Indications for Aortocoronary By- pass Graft Surgery · Exercise Programs in Rehabilitation of Patients with Coronary Heart Disease · Indications and Contraindications for Exercise Testing · Organ Donation and Transplantation · The Importance of Diagnostic Comput- erized Tomographic Scanning · Maternal Serum Alpha-Fetoprotein ~ . screening · Acupuncture · Electronic Fetal Monitoring · Continuous Ambulatory Peritoneal Di- alysis · Cochlear Implants · Percutaneous Transluminal Angioplasty In each case the Council appoints medical expert panels who are knowledgeable in the procedure and can address the issue in detail. These panels are usually comprised of 6 to 10 physicians. DATTA was instituted by the American Medical Association in 1982. All DATTA opinions appear in JAMA. The first DATTA reports were published in JAMA in 1983. The service is under the aegis of the AMA Council on Scientific Affairs. Purpose DATTA was developed for establishing a mechanism within AMA to briefly and promptly answer questions that might arise on the safety, effectiveness, and level of ac- ceptance in clinical practice of medical tech- nologies. Subjects of Assessment DATTA primarily assesses diagnostic and therapeutic procedures and technologies. Preventive and rehabilitative technologies 295 may also be assessed by DATTA, but they have not yet been subject to full assessments. Stage of Diffusion DATTA assesses new and existing technol- ogies. Possibly obsolete or outmoded technol- ogies also have been dealt with by DATTA, but they have not yet been subject to full as- sessments. Concerns DATTA assessments are concerned with the safety and effectiveness of diagnostic and therapeutic procedures and technologies, consonant with available peer-reviewed in- formation. Requests DATTA considers requests for assessment from any source as long as they are clearly stated in writing and focused so that a clear opinion can be rendered. Questions generally present matters of controversy in the clinical community. The AMA prefers that requests be accompanied by appropriate biblio- graphic references or suitable documentation that will help to justify the question. Selection The AMA responds to thousands of inqui- ries annually regarding information on as- sessment of diagnostic and therapeutic pro- cedures and technologies, particularly estab- lished technologies. Inquiries are handled by AMA staff, principally those in the two sci- ence divisions and the medical library. Those not appropriate for DATTA may be referred elsewhere within AMA for response. In addi- tion to DATTA, inquiries may be referred to the AMA library, the "Questions and An- swers" section of lAMA, the Council on Sci- entific Affairs, or other AMA councils and departments. The selection of questions for DATTA is made by staff under the direction of the DATTA Subcommittee of the Council of Sci- entific Affairs, which reserves the right to ac- cept, reject, or revise the wording of ques-

296 ASSESSING MEDICAL TECHNOLOGY TABLE A-3 DATTA Assessments and Technology Ratings, 1983-1985 Assessment Topic (JAMA volume:page) - 1983 Quantitative EEG [Fast Fourier Transform Analysis] Monitoring (250:420) No consensus Radial Keratotomya (250:420) Diathermy (250:540) Mandatory ECG Before Elective Surgery (250:540) Carbon Dioxide Laser Treatment of Gynecologic Malignant Neoplasms (250:672) Chelation Therapy for Atherosclerotic Disease (250:672) Implantable Infusion Pumpa (250:1906) Biofeedback (250:2381) 24-Hour Ambulatory EEG Monitoring (250:3340) Panel Rating - 1984 Whole-Body Hyperthermia Treatment of Cancera (251:272) Apnea Monitoring for Newborns at Risk of Sudden Death Syndrome (251:531) Cranial Electrostimulation (251:1094) Cardiokymography for Noninvasive Cardiological Diagnosis (251:1094) Diaphonography tTransillumination of the Breast] for Cancer Screening (251: 1902) Bone Marrow Transplantation in Childhood Leukemia (251:2155) Implanted Electrospinal Stimulator for Scoliosis (251:2723) Gastric Restrictive Surgery for Morbid Obesity (251:3011) Noninvasive Extracorporeal Lithotripsya (252:3301) Percutaneous Nephrolithotomy (252:3301-3302) Endoscopic Transurethral Nephrolithotomy (252:3302) 1985 Continuous Arteriovenous Hemofiltration (253:1325-1326) —for fluid removal in refractory fluid overload or acute renal failure —for uremia in acute renal failure Endoscopic Management of Gastrointestinal Tract Hemorrhage (253:2732-2735) —laser photocoagulation —thermal coagulation —electrocoagulation —topical therapy Diagnostic Intraoperative Ultrasound (254:285-287) Investigational Established Established Established Unacceptable Investigational Established Established Investigational No consensus Investigational/ unacceptable Investigational/ indeterminate, not acceptable Investigational Established (majority), investigational (minority) Investigational No consensus Investigational (78 % fib, other (22 ~o ~ Established (74 % ~b, investigational or indeterminate (26%) Investigational (78%)b, established (22%) Established (60 % ~b, other (40 % ) Established (53 % ), other (47 % ) "Published DATTA report cites panelists ratings by number and percentage of each of these four types of endoscopic treatments, as applied for each of three or four anatomic sites, respectively: esophagus, stomach-duodenum small intestine, and colon.]b Established (44 % ~b, investigational (42%), indeterminate (12%), unacceptable (2 % ) TABLE A-3 Continued on next page

APPENDIX A: PROFILES 297 NOTE: The DATTA reports and panel ratings in this table were published in the Journal of the American Medi- cal Association. See JAMA for full wording of DATTA topic questions and complete report narratives. The man- ner in which panel ratings are reported by DATTA has evolved since the program's inception. Panel ratings cited here do not fully reflect the discussions of DATTA opinions provided in the published DATTA reports. a Panel ratings have been suspended and assessments reopened for these technologies. The panel rating for whole- body hyperthermia treatment for cancer was updated in September 1984 to established for certain indications. ' Percentages cited for panel ratings reflect only those panelists offering opinions. For some assessments, more than half of the panelists surveyed offered no opinion. tions. DATTA will not undertake assessment of the safety and efficacy of a drug or medical device for a use that is included in FDA- approved labeling. It may, however, evalu- ate the safety, efficacy, and indications for use of a drug or device that are not included in FDA-approved labeling. Process Questions approved for DATTA are pre- pared by staff for evaluation by panelists. This includes stating the question so that it can be answered according to a standardized format. DATTA staff researches questions for background information in the neer- reviewed literature and seeks information on existing assessments (completed or in prepa- ration) from other organizations, including appropriate medical specialty societies. Where appropriate, information regarding regulatory status of drugs and medical de- vices is obtained from the FDA. Information on the subject of a question is made available to panelists on request to the AMA library, but otherwise does not accompany the DATTA questionnaire that is sent to panel- ists. DATTA panels comprise at least 40 physi- cians selected by DATTA staff from a large reference panel. Procedures or therapies which are the subject of DATTA questions are rated by the panelists as · established (limitations explained for general use, if appropriate); · investigational (limited to use under re- search protocol); · unacceptable; · indeterminate/no consensus to date (evi- dence insufficient for decision); or · no opinion (panelist has insufficient ex- perience with the technology). Panelists are also asked to comment on spe- cific knowledge of controlled trials, their ex- perience with the technology, overall bene- fits and risks associated with the technology, and special populations or patients for whom different ratings may be appropriate. Panel- ists do not review each other's opinions as a group. DATTA assessments are based upon the extent of agreement of the individual panelists. As is evident from Table A-3, pub- lished DATTA panel ratings have become more descriptive since the program's incep- tion. Since mid-1984, published DATTA as- sessment panel ratings have reflected divi- sions of opinion, and now do so in quantitative terms, including the number of panelists offering no opinion. In addition to the ratings of established, investigational, unacceptable, or indetermi- nate, DATTA opinions as published in lAMA include a narrative explanation of literature reports and panel findings. All DATTA opin- ions are reviewed and approved by the DATTA Subcommittee of the Council on Sci- entific Affairs. When a consensus cannot be reached on an especially important question, a special study, conference, or report may be called for by the Council on Scientific Af- fairs. DATTA opinions are sent to the ques- tioner, to the panelists queried, and to [AMA and other AMA publications as appropriate (see Reporting below). Assessors DATTA is operated by AMA staff under the direction of a subcommittee of four mem- bers of the Council on Scientific Affairs. Staff selects panelists for each DATTA assessment from a reference panel which comprises more than 600 physicians. The reference panel, representing a broad spectrum of major spe-

298 cialties and subspecialties, is appointed by the Council on Scientific Affairs. Panel mem- bers include those in practice, medical edu- cation, and biomedical research. Nominees are solicited from all segments of medicine, including state medical societies, medical specialty societies, the AMA Section on Medi- cal Schools, and other groups represented in the AMA House of Delegates and the AMA Councils. Panel composition is reviewed an- nually, and additional nominees are sought as specialty or geographic needs arise. Mem- bership in the reference panel is published as a matter of record, but the identity of indi- vidual panelists responding to a particular in- quiry is not disclosed by the AMA except with the express permission of the panelists and at the request of the Council on Scientific Af- fairs. Turnaround The time from selection of a question to the completion of a DATTA assessment is ap- proximately 4 to 6 months. DATTA panelists are asked to return their completed question- naires within 2 weeks of receiving them. Turnaround time is expected to be 3 to 4 months in 1985. Reporting Upon approval by the Subcommittee of the Council on Scientific Affairs, a final DATTA opinion on the technology in question is sent to the original questioner and to each panelist queried. DATTA opinions are also submitted to.TAMA and other AMA publications for dis- semination to the medical community. Publi- cation in the "Questions and Answers" sec- tion of JAMA makes 1)ATTA findings directly available to 343,000 U.S. sub- scribers, including AMA's 260,000 members, to 5,000 foreign subscribers, and to the in- dexed medical literature. In addition, the Council on Scientific Affairs publishes DATTA opinions in its annual reports. Each DATTA opinion is prefaced by the state- ment: "This report is not intended to be con- strued or to serve as a standard of medical care. It reflects the views of DATTA panelists and reports in the scientific literature as of Date of the report!.'' ASSESSING MEDICAL TECHNOLOGY Table A-3 lists the DATTA technology as- sessments and ratings published since the , · . program s Inception. Impact Given the size of the JAMA readership and the journal's inclusion in the indexed medical literature, opinions are available to a large readership. Although no assessment of DATTA's impact is planned, JAMA has re- ceived numerous letters to the editor com- menting on DATTA findings. Many of these letters cite new or previously uncited studies which are germane to DATTA topics ad- dressed in previous issues of jAMA. DATTA opinions are submitted to the AMA Board of Trustees and House of Dele- gates, which includes representatives from major U.S. medical societies. Membership may vote on accepting DATTA findings as official AMA policy, although none have come up as such as of this writing. Reassessment DATTA will reassess technologies, espe- cially those found to be investigational, based upon the publication or submission of signifi- cant new evidence. DATTA obtains monthly updates of major peer-reviewed journals and other reports to track the status of investiga- tional technologies. When the FDA approves a new device or a new indication for a device already in use on the basis of well-controlled clinical trials that demonstrate safety and efficacy, DATTA will reopen the assessment of any previously published DATTA opinion regarding that device or a related procedure to determine whether the conclusions remain valid. In those instances where the data and regula- tory judgment regarding device safety and ef- ficacy bear directly on the safety and efficacy of the clinical procedure involved, DATTA will publish an update notice reflecting cur- rent professional opinion and the basis for that opinion. Such a reassessment occurred following FDA approval (in January 1984) of labeling claims for specified palliative use of a hyperthermia system. An earlier DATTA opinion (published by AMA in October 1983 and appearing in .TAMA 251: 272, 1984) that

APPENDIX A: PROFILES found adjunctive use of whole-body hyper- thermia in the treatment of solid neoplasms to be investigational was reassessed in light of clinical trials data submitted to the FDA, and it was updated in September 1984 to reflect the FDA decision. DATTA has also reopened assessments of the implantable infusion pump, noninvasive extracorporeal lithotripsy, and radial keratotomy. Funding/Budget The AMA budget includes approximately $380,000 for DATTA in 1985. Example On the following pages is the DATTA re- port on continuous arteriovenous hemofiltra- tion. The report was published in the Journal of the American Medical Association, 253: 1325-1326, 1985, and is reproduced here with permission. Questions and Answers Diagnostic and Therapeutic Technology Assessment (DATTA) DATTA consultant physicians are asked to adrdrosa controversial and timely questions radiative to the aataty, etticacy. and Bud of acceptance in medical practir e of particular drugs, medical devices. and procedures. The con~nta affected ropr sent (1) persona in major reacting centers who ar considered to be knowb~eabie of the atate-ot-the-ar' as it pertains to the question; (2) areas of medicine where the drug, device, or procedure b used in practice; and (3) primary rare apoc~a~s wherein daily d~aions must be made about retiring patients for the type of seance in Creation. An effort is made to reflect a national geographic spectrum of diverse practice environments. This report is not intended to be Imbrued or to serve as a standard d medical care. n retiecta the views of DATTA panelists and replica in the sci - ffific literatur as of Oct 24. 1984. DATTA-rdated inquiries should be submitted to Nancy E. Cabill, Director, Technd~ As~sament, American Al ·~-tion, 535 N Dearbom c,. Cmcaec. ~ 606 10 Continuous Arteriovenous Hemofiltration QIs cornet nuous arteriovenous hemofiltration (CAVH) safe and effective therapy for the removal of Huid and uremic toxins from patients with refractory fluid overload or acute renal failure? A This question was submitted to 80 DACHA panelists; 30 offered an opinion. A majority (18/30) considered CAVH safe and effective ("established") therapy for fluid removal in either of the stated conditions. Sixteen of these same panelists regarded this technique as established for the treatment of uremia in acute renal failure. The 299 Sources American Medical Association. 1983. Reports of the Council on Scientific Affairs of the American Medical Association. 1982. Chicago. American Medical Association. 1984. DATTA Up- date on Hyperthermia Treatment for Cancer. Chi- cago. American Medical Association. 1985. Diagnostic and Therapeutic Technology Assessment (DATTA): An AMA Program of Medical Technology Assessment (program description). Chicago. Cahill, N., and J. Beljan. 1984. Technology assess- ment: Differing perspectives. Journal of the American Medical Association 252:3294-3295. Cahill, N. E., Director, Technology Assessment, American Medical Association. 1985. Personal com- munication. Jones, R. J., Acting Director, DATTA. 1983. Per- sonal communication. August 2. Jones, R. J. 1983. The American Medical Associa- tion's Diagnostic and Therapeutic Technology Assess- ment Program. Journal of the American Medical As- sociation 250:387-388. ~ Controlled hfu~on Fllid ~LScAb~ Shunt /: JO \~—Arm line ~ Hoister ~ W ,<3 / Hewn / ~ PUP " ,_ Graduated I Flltrate Cdbct~n Extracorporeal circuit for continuous arteriovenous hemofittration. Reproduced with permission from the Amicon Corporation, Danvers, Mass. remaining panelists offered no opinion because of insuffi- cient knowledge or experience with the technology. Continuous arteriovenous hemofiltration is an extracor- poreal process in which fluids, electrolytes, and other low-molecular weight substances are removed from blood by filtration at low pressure through hollow artificial

300 fiber membranes.'-3 The membrane allows passage of molecules smaller than albumin, producing an ultrafil- trate. This continuous process approximates the function of the renal glomerulus by using the patient's own arterial pressure to transport substances across a semipermeable membrane. The principles of this process differ from that of hemodialysis, which depends on diffusion of substances (plasma solutes) along a concentration gradient into a large dialysis volume. The rate of diffusion is proportional to the concentration of the solute and inversely propor- tional to its molecular size. Water (volume overload) is not removed by this process.4 Hemodialysis is more efficient than hemofiltration in clearing low-molecular weight substances such as urea, potassium, and creatinine but less efficient in removal of the medium-range sub- stances.4 Blood flow is established by placing a Quinton-Scribner or other arteriovenous shunt in the patient or by cannula- tion of the femoral artery and vein. The hemofilter cartridge is placed on-line. This unit contains thousands of hollow fiber filters made of polysulfone or polyamide. Blood entering the cartridge passes through the interior of the hollow fibers, where all substances less than a certain molecular size (water, urea, creatinine, and middle- molecular weight substances) pass through the filters The cellular components and species of the size of albumin or greater continue on to the venous exit port. Those substances that cross the filter make up the ultrafiltrate, and this is collected and drained into a calibrated urine bag via the ultrafiltrate port (technical data provided by Gambro Inc. Barrington, Ill, and by Amicon Corporation, Danvers, Mass). Heparin solution is infused into the arterial line, usually at the rate of 10 IU/kg of body weight per hour. Replacement fluid is infused into the venous line at a rate determined by the clinical setting. Edited by Hilde L. Slide, Assistant Editor. E—Y Lear must contain ~ I' name and add_, bat - _e ~ be omitted on request. Submined ._ are pubs ea apace pennies and at me di~bn d me editor. A11~ room a direct mail mpy. JAMA, March 1, 1985—Vol 253, No. 9 ASSESSING MEDICAL TECHNOLOGY The DACHA panelists emphasized that special groups of patients are candidates for CAVH, including those not suitable for hemodialysis because of hemodynamic insta- bility and those who require treatment of volume over- load.5b In CAVH therapy, the filtration rate decreases as the patient's blood pressure goes down. Therefore, hypo- tensive episodes are avoided. The dysequilibrium syn- drome is also avoided because there are no sudden shifts in body fluid compartments. Typical patients are those with multiple organ failure, including acute renal failure following surgery or severe trauma.7' Complications are those that may be encountered with any extracorporeal circuit need for vascular access, heparinization, and infection. The prefilter infusion of heparin does not significantly affect the patient's partial thromboplastin time or prothrombin time if there is no preexisting coagulopathy.9 However, in the patient with normal platelet counts and coagulopathy, even this small amount of heparin may induce bleeding., No studies have been reported that assess the relative merits of CAVH, hemodialysis, and peritoneal dialysis. The DATTA panelists found CAVH safe and effective. Clinical judgment must determine which patients would benefit from this therapy. 1. Henderson LW, Besarab A, Michaels A, et al: Blood purification by ultrafiltration and fluid replacement (diafiltration). Trans Am Soc A'tif Intern Organs 1967;13:216-226. ~ Bixler HJ, Nelsen LM, Bluemle LW: The development of disfiltration system for blood purification. Titans Am Soc Arty Intern Organs 1968; 14:99-108. 3. Kramer P. Seegers A, DeVivie R. et al: Therapeutic potential of hemofiltration. Clin Nephrol 1979;11:145-149. 4. Henderson LW, Silverstein ME, Ford CA, et al: Clinical response to maintenance hemodiafiltration. Kidne'/ Int 1975,2(suppl):58-63. 5. Kaplan A, Longnecker RE, Folkert VW: Continuous arteriovenous hemofiltration. Ann Intem liled 19&4;100:358-367. 6. Lauer A, Sacca~<gi A, Belledonne M, et al: Continuous arteriovenous hemofiltration in the critically ill patient. Ann intern pled 1983-,93:4 460. 7. Olbricht C, Mueller C, Schurek HJ, et al: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am Soc Artif Intern Organs 1982;28:33-37. 8. Paganini EP, Nakamoto S: Continuous slow ultrafiltration in oliguric acute renal failure. Trans Am Soc Artif Intern Organs 1980;26:201-204. 9. Kramer P. Bohler J. Kehr A, et al: Intensive care potential of continuous arteriovenous hemofiltration. Trans Am Soc Artif Intern Organs 1982;28:28-32. Questions and Answers 1325

Battelle Memorial Prostitute Human Affairs Research Centers 4000 N.E. 4Ist Street Seattle, WA 98105 (206) 525 3130 Major Emphases of Technology Assessment Activities Concerns Technology Safety Efficacy/ Cost/ Cost-Effect/ Effectiveness Cost-Benefit X X . X X . X X . . Ethical/Legal/ Socla Drugs Medical Devices/Equipment/Supplies Medical/Surg~cal Procedures Support Systems Organizational/Administrative X X X X X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded Application of Technologies X Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing * Clinical trials X Epidemiological and other observational methods X Cost analyses X Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $900,000 * Battelle participates in expanded clinical studies and trials by developing re- search protocols and collecting and analyzing safety, efficacy, and cost-effective- ness data. However, Battelle does not conduct its own clinical trials. BATTELLE MEMORIAL INSTITUTE HUMAN AFFAIRS RESEARCH CENTERS Introduction Established in 1929, Battelle Memorial In- stitute is an independent, nonprofit organiza- tion devoted to the advancement and use of science and technology. In addition to re- search and development in the physical, life, engineering, behavioral, and social sciences, Battelle manages programs and facilities and conducts educational activities and encour- ages the utilization of new inventions and dis- coveries. 30 Battelle has a staff of some 7,200 scientists, engineers, and support personnel at major re- search centers in its Columbus, Ohio, head- quarters and in Richland, Washington; Frankfurt, West Germany; and Geneva, Switzerland. Sites for specialized research and educational programs are located in Duxbury, Massachusetts; Houston, Texas; Seattle and Sequim, Washington; Washing- ton, D. C., and other sites around the world. The Battelle Human Affairs Research Cen- ters (MARC) is a component of the Pacific Northwest Division of Battelle Memorial In- stitute. Assessments of health care technologies are

302 undertaken by the Health and Population Study Center in Seattle. The Health and Pop- ulation Study Center also has programs in health care financing; policy planning and evaluation; chronic disease, disability, and long-term care; epidemiology and environ- mental health; physician behavior and medi- cal manpower; life-cycle transitions; work and the family; and social inequity. Purpose The purpose of Battelle technology assess- ments is to promote the advancement and ap- propriate use of medical technology. Specific objectives vary with assessments conducted for sponsoring agencies. For instance, the primary purpose of the National Heart Transplantation Study for the Health Care Financing Administration (HCFA) is to assist the agency to determine whether heart trans- plantations should be covered and reim- bursed under the Medicare program. Subjects of Assessment The primary emphasis of assessments thus far has been on medical/surgical procedures, although assessment activities focusing on ASSESSING MEDICAL TECHNOLOGY TABLE A-4 Battelle Health and Popula- tion Study Center: Selected Active and Re- cent Projects in Health Care Project Title (sponsor and end date) Cost-Effectiveness of Cyclosporine as Primary Im- munosuppressive Therapy for Kidney Transplant Recipients (Health Care Financing Administration, 1987) Performing Cost-Effectiveness Analysis: A Practical Guide for the Health Care Industry (1985) Survey to Identify Active Bone Banks (Naval Research and l:)evelopment Command, 1985) National Kidney Dialysis and Kidney Transplantation Study (Health Care Financing Administration, 1984) National Heart Transplantation Study (Health Care Financing Administration, 1984) Analysis of University of Southern California Data on Family and General Practitioners (University of Washington/Robert Wood Johnson Foundation, 1982) Estimate 1990 Manpower Requirements for Six Medi- cal Specialties (Health Resources Administration, 1982) An Analysis of the Impact of Physician Practice Ar- rangement on the Use of Drugs and Laboratory Tests (Health Resources Administration, 1981) Evaluation of the Process and Outcome of a Prospec- tive Management Team Approach to the Control of Pain in Cancer Patients (National Cancer Institute, drugs and medical devices have been initi- 1981) , . . Assist in Develonment of a Comnrehen.sive Health ated In Battelles Washington, D.C., office. Battelle's major recent health care efforts have been the broad assessments of heart transplantation and kidney dialysis and transplantation. As a part of these projects, Battelle has examined the government and private third-party payment mechanisms used for these expensive technologies. The role of the physician has been studied, in- cluding factors influencing physician produc- tivity, need for physician manpower, and physician distribution issues. Table A-4 lists selected active and recent Battelle projects in health care. Other studies have examined the economic and psychosocial consequences of chronic and catastrophic disease. For example, a re- cently completed project investigated the in- cidence and characteristics of pain associated with various types of cancer. A series of stud- ies have also been completed on the provision of long-term care in the nursing home indus- ~ ~ -r - Care Financing Plan for Alaska (State of Alaska, 1981) Implement Necessary Protocols for Estimation of Manpower Requirements for Eight Surgical Spe- cialties (Health Resources Administration, 1980) Examination of Rates of Return on Equity Capital and Risks in Nursing Homes under Medicare and Various State Medicaid Reimbursement Systems (Health Care Financing Administration, 1980) Analysis of the Content of Specialty Practices and Their Service Capacities (Health Resources Admin- istration, 1980) Study of the Relationships Between Case Mix and Fa- cility Staff Time and Costs for Direct Care of Nurs- ing Home Patients (Health Resources Administra- tion, 1979) try. Battelle has recently prepared a manual for the medical device industry to guide firms in conducting cost-effectiveness analyses of their products.

APPENDIX A: PROFILES Stage of Diffusion New and emerging technologies (e. g., heart transplantation) and existing technolo- gies (e. g., kidney transplantation and dialy- sis) have been assessed thus far, although technologies at any stage of diffusion would be considered for assessment. Concerns 303 medical device and drug manufacturers and their trade and professional associations. Selection Assessment topics are agreed upon by Bat- telle and its sponsoring organizations. Process The concerns of Battelle technology assess- ments vary among projects, but are generally those of the broader types of assessment. Technology need, availability, safety, effec- tiveness, cost, cost-effectiveness, and ethical and legal issues are explicit concerns of these assessments. Battelle is currently expanding its efforts in cost analyses of medical technol- ogies by encouraging the collection of cost data in clinical trials and developing industry guides for performing cost-effectiveness and cost-benefit evaluations of new and existing technologies. The National Kidney Dialysis and Kidney Transplantation Study is concerned with the quality of life, level of disability, quality of care, and cost of treatment associated with kidney dialysis and kidney transplantation. The National Heart Transplantation Study has been undertaken to determine the need for heart transplantation in the United States, the survival of heart transplant recipi- ents, the availability of donor hearts, the cost of performing a heart transplantation proce- m nt . cure, the rehabilitation and quality of life of e s. heart transplant recipients, and the legal and ethical issues surrounding heart transplanta- nology; tion. The Table A-5 listing of Update Series reports for the Battelle studies on heart trans- plantation and kidney transplantation and dialysis illustrates the range of concerns in- volved in these major assessments. Requests Much of Battelle's sponsored research is initiated from proposals of its own multidis- ciplinary teams. Other study topics come from organizations requesting Battelle's assis- tance for addressing specific problems, pri- marily federal agencies, foundations, and The procedures used by Battelle for con- ducting assessments of heart transplantation, kidney transplantation and dialysis, and other technologies are the following: 1. Identify technology to be assessed and prepare brief research protocol. 2. Establish a technical advisory panel made up of individuals who are familiar with the technology to provide assistance, on a consulting basis, in the evaluation effort. 3. Contact appropriate professional asso- ciations for representatives to provide input as needed. 4. Prepare a detailed research protocol, including background information on each technology, list of institutions or sources from which primary data are to be collected, a brief description of the data analysis plans, and schedule for project activities. 5. Collect data. 6. Analyze data. 7. Prepare final report. The assessments include the following ele- · an estimation of the need for the tech- · an analysis of the survival rates (if appli- cable) of the recipients of the technology; · consideration of the availability of the technology; · a complete analysis of the cost of the technology including a detailed analysis of the cost of alternative treatments for the dis- ease or condition in question; · a full assessment of the purported bene- fits of the technology including both objec- tive and subjective parameters; · a review and evaluation of any legal is- sues surrounding the technology, including regulation of use and distribution, selection

304 ASSESSING MEDICAL TECHNOLOGY TABLE A-5 Battelle Update Series for National Heart Transplantation Study and National Kidney Dialysis and Kidney Transplantation Study National Heart Transplantation Study Economic and Social Costs of Heart Transplantation (#3) Defining the Need for Heart Transplantation (#5) Patient Selection for Heart Transplantation (#6) Dimensions of Family Impact Pertinent to Heart Transplantation (#8) Title VI and Heart Transplantation: Discrimination in Patient Selection (#12) Survey of Hospitals with Open-Heart Surgery Facilities (#20) An Outline of Legal Issues in the Assessment of Health Care Technology: The Case of Heart Transplantation (#23) Fundamental Legal Rights and Governmental Regulation of Heart Transplantation (#26) Donor Organ Procurement Policies and Procedures Throughout the United States: A State-by-State Analysis (#31) The Present and Future Needs for and Supply of Organs for Transplantation (#33) Estimating the Costs of Organ Procurement for Heart Transplantation (#38) National Kidney Dialysis and Kidney Transplantation Study The Conceptualization and Measurement of the Social Costs of End-Stage Renal Disease (#11) Case-Mix, Treatment Modalities, and Patient Outcomes: Results from the National Kidney Dialysis and Kidney Transplantation Study (#14) Complexities in the Treatment of End-Stage Renal Disease: Economic Efficiency and Treatment Modality Pre- scription (#20) The Demographic Characteristics of the National Kidney Dialysis and Kidney Transplantation Study: A Com- parison with the End-Stage Renal Disease Population (#21) Peritonitis, Hospital Admissions, and Days Hospitalized Among Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) and Continuous Cycling Peritoneal Dialysis (CCPD): A Comparative Assessment (#24) A Comparative Assessment of the Quality of Life of End-Stage Renal Disease Patients on Four Treatment Modali- ties: Results from the National Kidney Dialysis and Kidney Transplantation Study (#26) Travel Costs and End-Stage Renal Disease (#30) NOTE: Battelle has printed about 80 reports in the Update Series' for the National Heart Transplantation Study and the National Kidney Dialysis and Kidney Transplantation Study, respectively. All are available from Bat- telle; a few have been published. The selected report titles listed here illustrate the range of concerns involved in these major studies. The respective Update Series report numbers are shown in parentheses. Of recipients, risk imposed on recipients, and so forth; · an analysis of the ethical concerns asso- ciated with the use of the technology, includ- ing patient selection, imposition of risk, dis- tributional concerns, etc. Assessors Battelle has a core staff of scientists from a variety of disciplines, including medical soci- ology, psychology, computer sciences, law, and health services, that are primarily re- sponsible for the conduct of studies. In addi- tion, Battelle has established working rela- tionships with outside individuals who serve primarily on advisory committees and tech- nical review panels, and who, in certain cases, are responsible for selected portions of the research. Staff assigned to assessments varies for each study. Major projects such as the heart transplantation study may involve as many as five full-time and eight part-time staff, plus 15 consultants and a review/advi- sory panel. Turnaround Turnaround time for studies varies. Bat- telle has undertaken numerous short studies, requiring a few months, at the request of HCFA and others which consist primarily of literature reviews and statistical compila- tions. Other studies take longer, such as the heart transplantation study (42 months) and the kidney dialysis and transplantation study

APPENDIX A: PROFILES (32 months). During the course of these longer studies, interim status reports (the Up- date Series) are made available. Reporting In addition to the final reports of assess- ments delivered to sponsoring agencies, Bat- telle publishes numerous interim reports in its Update Series. For example, about 50 up- date reports were made available for the heart transplantation study, and about 40 update reports were made available for the 3- year kidney study. HCFA has encouraged Battelle to disseminate widely reports on studies being carried out for that agency. Or- ganizations such as HCFA publish Battelle study summaries and reports conducted for those agencies in their publications. Battelle researchers also publish their findings in jour- nals such as Contemporary Dialysis, Heart Transplantation, Journal of the American Medical Association, Journal of Health Poli- tics, Policy ~ Law, Lancet, New England Journal of Medicine, and Science. Impact Although there is no tangible evidence for direct impact of studies, there are other indi- cations that the Battelle projects are of inter- est. Study personnel are often asked to partic- ipate and make presentations at conferences (e.g., NIH Consensus Development Confer- ences) and before congressional committees and subcommittees, state governments, and other policymaking bodies. Funding/Budget The total annual research budget for the Health and Population Study Centers has been approximately $2 million-$2.5 million in recent years. Funding for technology as- sessment activities has been approximately $900,000 annually in recent years, most of which has been for the heart transplantation and kidney studies funding by HCFA. Example The following is a summary description of the National Heart Transplantation Study 305 undertaken by Battelle Human Affairs Re- search Centers. This summary is the full text of "Update Series #1, The National Heart Transplantation Study" (February 22, 1982), available from Battelle, Seattle. NATIONAL HEART TRANSPLANTATION STUDY Overview The National Heart Transplantation Study is a cooperative study involving several major heart transplant programs across the United States. The major objective of the study, more completely delineated below, is to ex- amine all aspects of heart transplants, includ- ing the scientific, social, economic, and ethi- cal issues, and, in particular, the impact of a possible Medicare decision to pay for heart transplants on the Medicare program, Medi- care beneficiaries, and providers of health care. In particular, the study will focus on seven major areas. These are: (1) the estima- tion of the potential need for heart trans- plants, (2) the survival of heart transplant re- cipients, (3) the potential availability of donor hearts, (4) the cost of performing heart transplants, (5) the rehabilitation and quality of life of heart transplant recipients, (6) the legal, and (7) the ethical aspects of heart -transplantation. It is expected that the study results will have implications for the promul- gation of Medicare policy with respect to heart transplantation. The National Heart Transplantation Study is to be conducted over an 18 month period beginning in October, 1981 and ending in April, 1983, is funded by the Office of Re- search and Demonstrations of the Health Care Financing Administration (HCFA). The study is being directed by Dr. Roger Evans of the Health and Population Study Center at the Battelle Human Affairs Re- search Centers in Seattle, Washington. Background In November, 1979, the Health Care Fi- nancing Administration authorized Medicare payments for heart transplantation proce- dures performed for Medicare beneficiaries

306 at Stanford University Medical Center. This was an interim decision, based on prelimi- nary findings by the Public Health Service (PHS) regarding the safety and efficacy of heart transplants performed at that center. HCEA anticipated when reimbursement was tentatively authorized, that it soon would be able to reach a final decision not only about coverage at that center, but also on generally applicable, broadly based criteria for ap- proving Medicare coverage of heart trans- plantation at other facilities. As HCFA proceeded to review Medicare coverage of heart transplants, it was deter- mined that the issues were much more com- plex than originally thought and that many of them could not be immediately resolved because adequate data did not exist. There were numerous questions, for example, con- cerning the patient selection process, the ba- sis for assessing safety and efficacy, the long- term social and economic consequences of the procedure, broad ethical considerations, the cost-effectiveness of the procedure, and the potential, if any, for substantial expansion in the availability of heart transplantations. It was concluded that HCFA did not have suffi- cient information at this time to support the development of generally applicable cover- age criteria. On June 12, 1980, Patricia Roberts Harris, then Secretary of the U.S. Department of Health and Human Services (DHHS), an- nounced a decision to exclude heart trans- plants from Medicare coverage, with the ex- ception of a very few patients previously selected for and awaiting transplants. This announcement was published in the Federal Register on August 6, 1980 (Volume 45, No. 153, Pages 52296-S2297~. At this time, Harris announced that all new technologies must be evaluated not only on the basis of their medical efficacy but also on the basis of their "social consequences" before "financing their wide distribution." The approach being suggested by Harris was even more compre- hensive than that used by, for example, the Environmental Protection Agency (EPA) in dealing with pesticides, the Food and Drug Administration (FDA) in its treatment of pharmaceuticals, and the Occupational Safety and Health Administration's (OSHA) ASSESSING MEDICAL TECHNOLOGY approach to carcinogens in the workplace. New health technology was to be evaluated concerning its cost-effectiveness, cost-benefit ratios, and its "long-term effects on society." The decision to exclude heart transplants from Medicare coverage was accompanied by an announcement that HCFA, in close co- operation with the Public Health Service's National Center for Health Care Technology (NCHCT) would conduct a broad study of the sort described by Harris. This study, now referred to as the National Heart Transplan- tation Study, was to address all of the issues identified above including the scientific, so- cial, ethical, legal, and economic issues. As already stated, the study was also to examine the impact of a potential coverage decision on beneficiaries, the Medicare program, and health care providers. The institutions or clinical centers chosen to participate in this study have been selected very carefully. In reviewing the applications submitted by the clinical centers, it was, a priori, determined that cardiac transplanta- tion could not be considered as simply a sur- gical procedure. It was further decided that clinical effectiveness and usefulness are de- pendent upon careful and appropriate pa- tient selection, expert surgery, post-operative care, immunosuppression, evaluation for in- cipient rejection of the donor heart, manage- ment of complications associated with im- munosuppression, patient education, and liaison with the patient's permanent physi- cians for subsequent lifelong care. Criteria for the selection of participating clinical cen- ters were developed by the National Heart, Lung and Blood Institute, with the advice of an advisory group of experts in cardiology, cardiovascular surgery, organ transplanta- tion, and immunology. Three major criteria were specified for the selection of clinical centers. They were: (1) the institution must have had experience with a clinical heart transplant program within the past five years, (2) the institution must have adequate patient selection criteria, and (3) the institu- tion must have adequate patient manage- ment plans and protocols. All participating clinical centers (i. e., heart transplant programs) will be expected to furnish, or facilitate access to, a wide vari-

APPENDIX A: PROFILES ety of data regarding heart transplants previ- ously performed at their facilities during a period starting no later than January 1, 1975, and continuing over the 18 month period of the study. This will include data on each in- stitution's facility and personnel resources, heart donor program, patient selection crite- ria, transplant and patient care protocols, patient follow-up care, patient survival, costs of establishing and maintaining a heart trans- plant program, patient charge information, and other similar and related information. 307 Sources Battelle. 1983. Battelle: Seeking Solutions to Signif- ieant Social Problems. Seattle. Battelle Human Affairs Research Centers. 1982. The National Heart Transplantation Study (Update Series #1~. Seattle. Evans, R. W. 1983. Organ transplantation. Sei- enee 222:232. Luee, B., Senior Research Scientist, Battelle, Washington, D. C. 1985. Personal communication. Overcast, T. D., Senior Research Scientist, Bat- telle. 1985. Personal communications.

Introcluction to Blue Cross and Blue Shield Association Blue Cross and Blue Shield are the names and symbols used by the 87 local, nonprofit plans that contract with hospitals, physi- cians, and other health care providers and fa- cilities to provide prepaid health care services to their subscribers. The Blue Cross plans pri- marily cover hospital expenses, though they have expanded coverage into outpatient care. The Blue Shield plans primarily cover physi- cians' services, though they have expanded into such benefits as dental, vision, and out- patient services. Some local Blue Cross and Blue Shield plans are jointly operated. The Blue Cross and Blue Shield organization is not a single company; rather, it is a nation- wide federation of locally governed, autono- mous corporations, each operating under state law as a nonprofit service organization. There are about 80 million regular Blue Cross and/or Blue Shield plan subscribers, in- cluding subscribers under the Federal Em- ployee Program and coverage supplementing Medicare. Approximately 29 million people are served by plans in their roles as interme- diaries for Medicare Part A, and as carriers for Medicare Part B. Medicaid, and CHAM- PUS (Civilian Health and Medical Program of the Uniformed Services). Eliminating du- plication between the programs, the total number of people served is about 100 million. In 1983, Blue Cross and Blue Shield plans paid $34.6 billion for care received by plan subscribers, and another $38.2 billion was paid for persons in federal programs. The local Blue Cross and Blue Shield plans have medical departments and engage in varying levels of technology review activities. The California Blue Shield Medical Policy Committee assesses for coverage purposes new diagnostic and therapeutic technologies, and initiated the review of obsolete proce- dures that grew into the Medical Necessity Program of the Association. Beginning in 1982 with percutaneous transluminal coro- nary angioplasty, California Blue Shield be- came the first private third-party payer to 308 institute selective reimbursement i. e., payment for certain procedures at designated institutions only and currently reimburses selectively for heart transplants and liver transplants. The Blue Cross and Blue Shield Associa- tion is a coordinating agency of the plans. The Association speaks on behalf of the plans on matters of national concern and operates programs of public education and profes- sional relations. It also works with plans on cost-containment efforts and provides re- search, statistical, actuarial, marketing, and other services to the plans. The Association administers plan membership standards and maintains a computerized telecommunica- tions system linking all the plans. The Associ- ation helps to coordinate the uniform admin- istration of health care coverage for large national employers with plants and offices in more than one region, and is the prime con- tractor for the organization's administration of Medicare Part A. Notwithstanding the na- tional coordinating role of the Association, local plans are responsible for making their own administrative and coverage policy. In addition to the Medical Necessity Pro- gram and the Technology Evaluation and Coverage Program described in the following profiles, the Blue Cross and Blue Shield Asso- ciation supports other organizations in their technology evaluation efforts. For example, it commissioned an Institute of Medicine study of the effectiveness of computed tomo- graphy (CT) scanning, and provided funding for a Conference of Medical Specialty Soci- eties on technology assessment in 1981. The Blue Cross and Blue Shield Association does not conduct its own original clinical re- search. Blue Cross of Massachusetts has obli- gated over $5 million in matching funds to the Massachusetts Fund for Cooperative In- novation, a grant program for hospital cost- containment experiments administered joint- ly with the Massachusetts Hospital Associa- tion.

Medical Necessity Program Blue Cross and Blue Shield Association Technology Management Department 676 North St. CIair Street Chicago, TE 60611 (312) 440 6155 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative Stage of Technologies Assessed Emerging/new X Accepted use X Possibly obsolete, outmoded A p plication of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $350,000* * This amount represents the Association?s expenditures for technology man- agement and coding processes, and related activities. Included are significant por- tions devoted to implementing the Medical Necessity Program and the Technol- ogy Evaluation and Coverage Program. MEDICAL NECESSITY PROGRAM BLUE CROSS AND BLUE SHIELD ASSOCIATION Introduction Most Blue Cross and Blue Shield plan ben- efit contracts contain a medical necessity clause which provides that services are cov- ered when they are medically necessary. When a technology is properly used and is covered by the contract, it will be paid. The 309 plans view as medically unnecessary certain technologies used inappropriately or simply due to routine. The Medical Necessity Program (MNP) rests on the assumption that physicians prefer to practice good medicine, but not all are aware of more recent clinical developments. The program recognizes the difficulty in es- tablishing rules for clinical treatment to which there are no exceptions, and provides that technologies addressed in the program

310 will be paid for if their use is justified by a . . P Scan. The identification of obsolete procedures by Blue Cross and Blue Shield plans began in 1975 with the California Blue Shield's Medi- cal Policy Committee. The Blue Cross and Blue Shield Association Medical Necessity Program was begun in 1977 as one of the first national private initiatives to assess medical technology for coverage purposes, in cooper- ation with the American College of Physi- cians, the American College of Surgeons, and the American College of Radiology. An out- growth of the Medical Necessity Program is the Clinical Efficacy Assessment Project of the American College of Physicians. Purpose The purpose of MNP is to provide informa- tion to member plans to assist them in deter- mining their subscriber contractual obliga- tions which require reimbursement only for necessary medical care. Plans will pay for any recognized procedure found necessary by the admitting physician, but view as medi- cally unnecessary certain clinical practices performed simply out of routine or habit. For plans that adopt the Medical Necessity Pro- gram guidelines, the program "shifts the bur- den of proof" from payer to provider in that providers must justify their use of procedures and services falling outside of MNP guide- lines. MNP guidelines are not statements of Blue Cross and Blue Shield coverage; terms of individual plan contracts govern such cover- age. Concerns Subjects of Assessment The Medical Necessity Program deals pri- marily with medical and surgical procedures. Many of these entail the use of drugs and medical devices, but the emphasis of the as- sessments is on the indications for use of the drug- or device-embodied procedures, rather than on the attributes of the medical prod- ucts as such. With the initiation of the pro- gram in 1977, 42 diagnostic and surgical pro- cedures were identified as outmoded or of unproven value. The second phase of the pro- gram called for the elimination of routine ASSESSING MEDICAL TECHNOLOGY laboratory and x-ray testing at the time of hospital admission. As of 1985 there were nearly 90 procedures on the outmoded proce- dures list. With the development in 1982 of MNP guidelines for respiratory therapy, the scope of the program was expanded to deal with procedures that may be overutilized or inappropriately used. The Medical Necessity Program has devel- oped guidelines on the following clinical is- sues: · outmoded procedures list (1977) up- dated periodically · routine admission testing policy (1979) · respiratory care guidelines (1982) · diagnostic imaging guidelines (1984) · cardiac care guidelines (1985) The program is currently developing guide- lines on clinical laboratory and pathology services and on the use of chest x ray and elec- trocardiogram in hospital admission and pre- operative evaluation. Stage of Diffusion The Medical Necessity Program originally focused on technologies that were outmoded or unproven. The program has since ex- panded its focus to include procedures and services that are standard practice, but are utilized in inappropriate circumstances or more often than warranted by good medical practice. Of primary concern are the clinical effec- tiveness and specific indications for use of a technology for physician education and cov- erage purposes. The Medical Necessity Pro- gram is intended to curtail the unnecessary use of certain procedures. Although cost and cost-effectiveness of technologies have not been explicit concerns of the program, it has recently begun to consider cost-effectiveness for selected procedures such as chest x rays. Requests The MNP addresses questions that are raised directly by local plans, and may inde-

APPENDIX A: PROFILES pendently initiate a review of topics which have implications for all plans. Selection Issues having highest priority are those that may have the greatest impact on all plans and those that may require immediate attention by the plans. Plans are advised of issues that will be considered by the program. Process The Association commissions critical evalu- ations of existing medical literature by recog- nized experts and seeks clinical opinions of rec- ognized medical specialty societies. The medi- cal specialty societies are responsible for supplying the clinical expertise on various pro- cedures and services; the Association's respon- sibility is to disseminate this medical consen- sus. The Association convenes periodic national conferences and invites national medical specialty society representatives for the purpose of soliciting clinical opinions. In all cases, the Association's position or guide- lines consider its evaluation of existing medical literature and the opinions of the Association's Medical Advisory Panel. The guidelines are reviewed by the Medical Advisory Panel and are approved by the Association's board. The Association does not conduct original clinical research to determine clinical efficacy and in- dications. Sensitivity in administration of MNP guidelines is used. For example, plans will view hospital regulations that call for admis- sion batteries as meeting the MNP hospital admission tests battery requirement, pro- vided that the hospital staff has studied the needs of its patient population and has lim- ited the battery to those tests required by a significant majority of admitted patients. An important aspect of the MNP is the edu- cation of health professionals regarding new guidelines. In the case of the MNP guidelines for diagnostic imaging issued in 1984, infor- mation regarding the new guidelines was to be made available to health care providers for a period of 6 to 12 months, after which several plans may start disallowing payments for procedures not meeting the guidelines. 311 Assessors The Medical Advisory Panel consists of about 10 members and is selected by the se- nior staff of the Association. Most members are plan medical directors, primarily of the larger plans, and represent a mixture of spe- cialties, geographic locations, and back- grounds in clinical practice, academe, and administration. The Association has cooperated with a number of medical societies in the Medical Necessity Program. These have included the following: American Academy of Dermatology American Academy of Family Physicians American Academy of Neurology American Academy of Pediatrics American Association of Neurological Sur- geons American College of Nuclear Physicians American College of Obstetricians and Gynecologists American College of Physicians American College of Radiology American College of Surgeons American Psychiatric Association College of American Pathologists Society of Nuclear Medicine The medical societies that participated in writing MNP guidelines are generally cited in the respective guidelines or in accompanying press releases. Turnaround It takes approximately l year from the time of designating a subject for consider- ation by the program to the time that the MNP guidelines are formally approved and distributed. Reporting The guidelines developed by the MNP of- ten are announced in national press confer- ences. Guidelines generally include the fol- lowing: 1. brief description of the technology; 2. policies regarding specific clinical indi-

312 cations for use and nonuse of the technology; and 3. further policy considerations or ration- ale supporting policies. Medical Necessity Program guidelines are transmitted directly to plans by the Associa- tion's TEC Newsletter and various plan bul- letins. The guidelines are provided by many plans to area physicians who provide care to subscribers and to other requesting parties. Reassessment The Association will reassess MNP guide- lines when it is apparent that new clinical ev- idence exists and clinical opinions have changed sufficiently to warrant revised guidelines. This could be the case for proce- dures once considered to be standard practice later found to be obsolete, or for procedures first determined to be obsolete which are later found to be rarely yet appropriately used. An example is radical hemorrhoidec- tomy (whitehead type), which was cited in the MNP procedures list in 1977 and deleted in 1980. Impact The Association does not systematically track the impact of MNP guidelines. Because of contract variations, hold harmless orovi- sions (i.e., where a subscriber is not held fi- nancially responsible for care provided out- side of MNP guidelines), state-legislated mandates, and local practice variations, the impact of the MNP guidelines probably var- ies among plans. When introducing new MNP guidelines, the Association has cited the overall magni- tude of expenditures devoted to the general area of health care involved, e.g., $10 billion devoted annually for diagnostic radiology (Blue Cross and Blue Shield Association, 1984b) and $2 billion-$4 billion spent annu- ally for hospital respiratory care services (Blue Cross and Blue Shield Association, 1982~. All plans are advised to seek justifica- tion before denying payment for services that fall outside the MNP guidelines. In 1977, the Medical Necessity Program ASSESSING MEDICAL TECHNOLOGY announced that 42 outmoded diagnostic tests and surgical procedures should no longer be performed. According to early analyses, if the program's policies regarding these out- moded procedures were fully implemented through 1981, they could have resulted in an estimated $300 million annual savings (see Greenberg and Derzon, 1981~. These esti- mates have not been followed up by broad- based studies of actual savings, however. A review of a sample of insurance claims for portions of the Federal Employee Health Benefits Program administered by Blue Cross and Blue Shield plans in 1975 and 1978 showed a decline in claims for listed surgical procedures of 26 percent and a decline in di- agnostic test claims of 85 percent (Blue Cross and Blue Shield Association, 1982~. How- ever, without earlier points of reference, it is difficult to attribute the decline in tests in surgery to the issuance of the MNP guide- lines. The impact of the MNP was cited in a 1980 report of the General Accounting Office (GAO). Upon studying the MNP, the GAO concluded that medical necessity programs can reduce health care costs, and the agency recommended that the federal government's Office of Personnel Management adopt simi- lar policies throughout its Federal Health Benefits Program. Using data from eight local hospitals, Blue Cross and Blue Shield of Oregon estimated that implementation of the Medical Necessity Program routine hospital admission testing policy resulted in a savings of $22 per admis- sion, and that full implementation on an area-wide basis would result in a projected savings of $8 million. Funding/Budget The Association devotes approximately $350,000 annually to its technology manage- ment and coding processes, including the MNP and the Technology Evaluation and Coverage Program. The Association offers this technical assistance as part of its ongoing support to plans, and does not charge plans a user fee.

APPENDIX A: PROFILES Examples 1 On the following pages are excerpts from three types of Medical Necessity Program guidelines. The first is a page out of the Medi- cal Necessity Procedures List, showing 10 di- agnostic procedures requiring satisfactory justification (for payment, as recommended by the Association) and the specific reason for their inclusion in the list. The inclusion of these particular 10 procedures was endorsed by the College of American Pathologists (CAP) and the American College of Physi- cians (ACP). The second example is the Med- ical Necessity Program statement regarding hospital admission test batteries. The third example is excerpted from the 1985 MNP guidelines on cardiac care, and includes the cover sheet, table of contents, and guidelines on echocardiograms, 1 of 13 procedures ad- dressed in that set of guidelines. Sources Blue Cross and Blue Shield Association. October 12, 1982. Press release: Blue Cross and Blue Shield Association Issues Guidelines on Respiratory Care. Chicago. Blue Cross and Blue Shield Association. Medical 313 Necessity Procedures List. Revised according to BCBSA 81 coding and nomenclature. Revised June 1983. Chicago. Blue Cross and Blue Shield Association. 1984a. Questions and Answers about the Blue Cross and Blue Shield Organization. Chicago. Blue Cross and Blue Shield Association. 1984b. Press release: Blue Cross and Blue Shield Association Issues Guidelines to Reduce Diagnostic Imaging Pro- cedures. Chicago. Blue Cross and Blue Shield Association. 1985. Med- ical Necessity Guidelines on Cardiac Care. Chicago. Blue Cross of Massachusetts/Massachusetts Hospi- tal Association Fund. 1985. Blue Cross/MHA Fund for Cooperative Innovation: Report for 1984. General Accounting Office, U.S. Congress. 1980. The OPM Should Promote Medical Necessity Pro- grams for Federal Employees' Health Insurance. Washington, D.C.: U.S. Government Printing Of- fice. Greenberg, B., and R. A. Derzon. 1981. Determin- ing health insurance coverage of technology: Prob- lems and options. Medical Care 19:967-978. Morris, L. C., Senior Vice President, Health Bene- fits Management, Blue Cross and Blue Shield Associa- tion. 1985. Personal communications. Schaffarzick, R., Senior Vice President and Medi- cal Director, Blue Shield of California. 1985. Personal communication. Tennenbaum, D., Manager, Medical Necessity Program, Blue Cross and Blue Shield Association. 1985. Personal communications.

314 U] C) Cal U C) C) C) U ~ C: Cal ~ ~ ~ ~ ~ ~ =~ S ~ A: o ~ ~ ~ P4 ~ ~ P4 ~ ~ ~ ~ Z ~ ~ ~ ~ <: A: < o ~ ~ C: C) Cal ~ Cal ~ U Cal U ~ Co Z - . a' so: O ~ 1 ~ ~ ~ 1 .. . - . - ~ o ~ oo ~ ~ ~ o O . - ~ ~ ~ ~ E .,, ~ ~` C: v a, v 0 U ~ ~ ~ ~ V E a~ ~ 5 ~ ~ oe ~; U: ~ ~ ~ s~ >, 0? t~ tO 4) ~ ~ E o O >: U~ C) O U E Z ~ ,~ >, v ~ ~ Q O · - ~ ~ ~ ·e O ~ ~ ~ O ~ ~ 3 ~ N _' ~ u] a~ ~5 ~: ~ to ~ ~ ~-— E <: u, ~ a, :5 ~ ~ ~ ~ ~ ~ v 03 ~ U V ~ ~! U ~ ~ ·— ~ CY Q5 ~ U ~ G5 ~ O Q. O ~ ~ tl] H 3 >. ~ C) n5 C: ~ ~ U~ ·— U] ·-~ U] G) 3 Ei C: ~ Q4 ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1— ~ O ns ·— a~ a) 0 ~ G5 ~ ~ ~ ·— a~ 0 6~ ~ ~ ~ ~ ~ ~ ~- - —~ ~ ~ ~ ~: ~ s~ C~) H V O n; a) Q Q to tt O a; Z Z O · - ·' ~ ·' E V ~ ·' tO ·' ·' ·' E 0 ~ f~ c: 0~ 0 a) ~ Q ~ ~ ·— a) a~ ~ ~ a) ` H ~ ~ . - == ~ ~ ~ ~ ~ ~ ~ == == ~ ~ a O cn ~ a) a) c: ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ U] Z V ~ ~ ~ 0 ~ ~ - - - ~ ~ ~ ~ ~ ~ 0 H H O O O · - V ~ ~ O ~ O ~ 0 3 0 · - ~ ~ a ~ u: 0 Ul ~ ~ Ul u~ ~ JJ ~Q V v' ~ u, v O Z O Q ~ Q ~ O ~ G) Q-- O Q ~ Q V Q ~ u: u: <: ~ Z O tQ O S:: Z ~ ~ O ~ Z O tO O n5 0 t: U] ~ O 5: cr: 3Z ~ aaH ,5 ~ C~ O ·,. ~ H O ~) ~ ·,4 ~ ~ ·~1 U: P~ ~ ~ V ~ CO 01 ~ U] 1~ ~ 3 ~1 X 0) 3 ~ ~ CO S m u: m :^ ~ E ~ ~ ~ U] ~ ~ O · - ~ ~ V a ~ cr O ~ ~ u' ~ u: ~ Z C: ~ JJ ~ ~ cn ~: ~ 0 V C) ' ~ — ~ S~ Z E~ ~ a' ~ ~5 0 ~ ~ · - u: ~ (9 z O: a) ·-l 0 ~ u, Q ~ O ~ Z O .- J~ —~ O U) t2J ~ C ) H H ~ ' tIS C) V 0) C: H ~ E~ G' U] ~ _! a =; ~ u, ~ .- ~ ~ a' ·- ·- H E ~ c ~ Q C C £ C: ~ ~ >, ~ O ~ 3 0 0 ,:1 O (~) ~ N ~ ·—l 0) ~ ·~/ ·—I m ~ u, .- 0 rs ~ ~ ~ ~ u2 ~ ~ O ~ O O ~r ·~- · - _1 3 ~ U2 ~ _ 1 ~ 3 ' :5 ~ ~! O · - C) U] ~ ~5 U) V O O U] H 0) O 0) V O ' —i >1 ' ' ~ ~ O V O ~ ~ Q ~ ~ ~ ~ O ,~ O ~ Q · - tt5 · - ~ R:5 ~ O U~ Q (l~J kLI U) ' C Q4 O a) ~ ~ ~ ~ C ~ 0~- ' ' ~ ~ E ~ ~ 5,-.- s 8 ~ ~ · - ~ ~ ~ v 4U 4J ~ ~ a' .` ~ U] 3 E ~! ·— ~ o ~ o u, >, ~ ~ · - · - ~ ~ O O ~ ^ ~ ~ ~ ~ ~ ' V ~ V ~ s O ~ ~ ~ ~ ~ ~ ~ - O ~ ~ ~ ~ ~ ~ ~ U) 3 S~ Q5 C ~ Q5 ~ O E ~ Q~ c' s s O c5 ~ O 3 0 ~s: C) tQ ~ O C) C: ~ Q C~ ~ ~ u: C~ ~ ~ .. O V =1 ~ a) ~ 31 c 4~ 0 ~ ~ _ ~ Z CO ~ ~ ~ 11:1 ~ ~ U] 3 ~ C) tn ~ ~— o tn o ~ r~ <;5 u~ o Q 1~ Z ~ u~ ~ Co ~ o ~ ~ ~ ~ o ·~- - C) ¢ ~ ~ 3 ~ ,- <~ cn ~ ~ ~n <~ ~ ~ o O? t~ m U~ C: 0 0 ~ C~ ~ C~ ~ ~ ~ ~ C~ ~ ~ ·~-— ~ O O Z ~ c:~ co co co ao oo ao oO ~ ~ ~ ~ 11 C) o:: Z . ~ ~ ~ ~ <: + + + ~ =: +

APPENDIX A: PROFILES BLUE CROSS AND BLUE SHI ELD ASSOCIATION MEDICAL NECESSITY PROG~I HOSPITAL ADMISSION BATTERIES I. Hospital Admission Batteries batteries for medical Section; 2-MLIP Page: 1 of 1 In February, 1979 the Blue Cross and Blue Shield Assoc~ ation, based upon advice from the American College or Physicians, recommended to Plans that routine no:~;pital d iagnostic _ _ ~ admission be added to the Medical Necessity Project. Two months later, upon the advice of tne American College of Surgeons, tnat recommendation was extended to include surgical admissions. A. Medical Admissions 1. The American College of Physicians recommends tnat diagnostic tests should not be required as routine procedures for patients admitted to a Hospital. Examples ~ of routine diagnostic admission tests may i nc 1 ude t he f o l low i ng: blood hemog lobi n urine analysis biochemical blood screens chest x-ray e lectrocard iogram Given the American College of Physicians' policy concerning diagnostic tests, the Blue Cross and Blue Shield Association recommends tnat Plans: Continue to provide benef its for tests performed for a patient admitted to a hospital for medical treatment but only upon evidence tnat tne tests were ordered by an attending or admitting physician s~?ecif ically for that patient . B . Surg i Cal Ad mi ss ions 1. The American College of Surgeons stated tnat the routine use of batteries of tests without speck f~c orders on admission should apply to surgical as well as medical cases. Diagnostic admission tests ordered for the pre-operative patient require discrimination by the physician. . 2. Based on this advice from the American College of Surgeons, the Blue Cross and Blue Shield Associate on recommends that Plans: Continue to provide benef its for tests performed for a patient admitted to a hospital for surgical treatment but only upon evidence tnat tne tests were ordered by an attending or admitting physician specif ically for tnat patient . Revision number: 1 Revision Date: 6/8 3 315 Date of issue: 1979

316 ASSESSING MEDICAL TECHNOLOGY MEDICAL NECESSITY GUIDELINES SUE BECTION 5-MNP-85 CARDIAC CARE ~~;l 1 0 f 1 5 MEDICAL NECESSITY GUIDELINES ON CARDIAC CARE BLUE CROSS AND BLUE SHIELD ASSOCIATION These Guidelines have been issued as part of the Blue Cross and Blue Shield Association's Medical Necessity Program. They have been developed in cooperation with medical specialty societies and the Blue Cross and Blue Shield Association for use by the Blue Cross and Blue Shield Plans. REVISION NO. REVISION DA" Date of Issue: 2-1-85

APPENDIX A: PROFILES 317 MEDICAL NECESSITY GUIDELINES SUBJE~ SE=10N 5-MNP-85 PAGC CARDIAC CARE 2 of 15 . TABLE OF CONTENTS Page 1. Cardiac Exercise Stress Test ~ ~ e e e e e e ~ e e e e e e e e e ~ e e e e e 3 2e Outpatient Cardiac Rehabilitation e e e e e e e e e e e e e e e e e e e 4 3 e Intens*e Cardiac Care Unit e e e e e e e e e e e e e e e e e e e e e e e e e 5 4e Permanent Cardiac Pacemakers e e e e e e e e e e e e e e e e e e ~ e e e e e 6 5e Coronary Angiography and Cardiac Catheterization eeee 10 6e Echocardiogram e e e e e e e e e e e e e e e e ~ ~ e e ~ e e e e e e e e e e e e e e e e e 12 7 e Electrocardiogram e e e ~ e e e e e e ~ e e e ~ e e e e ~ e e e e e e ~ e ~ e e e e e a 13 8e Anticoagulant Therapy in the ~yocardial Infarction Patient . e e e e e ~ ~ e e e e e e e e e e e e e e e e e e e e e e e e 13 9e Serum Lipoprotein Evaluation ~ e e e e e e ~ e e e e e ~ e e e e e e e e e e 14 10 e Cardiokymography ~ e e e e e e e e e e e e ~ e e ~ e e e e e e e e e e ~ e e e e e e e ~ 14 11 e Doppler Flow Velocity Study . e e e e e e e e ~ e e e ~ e e e e e e e e e e e 14 12 e Vectorcardiogram ~ e e e e ~ e e e ~ e e e ~ e e ~ ~ e e ~ e e ~ ~ e ~ ~ e e ~ e ~ e e e 15 Most health benef its coverage excludes procedures used to screen asymptomatic persons for evidence of disease e The omission of any such screening procedures from these Guidelines does not ref lect any judgment about the appropriateness or desirability of such public health measures. Similarly, these Guidelines are not and should not be construed as a statement of Blue Cross and Blue Shield coverage for the procedures and services discussed herein. The teens of individual Plan contracts govern such coverage. REVISION NO. REVISION DA" Date of Issue: 2-1-85

318 ASSESSING MEDICAL TECHNOLOGY MEDICAL NECESSITY GUIDELINES BUBJE~ CARDIAC CARE SECTION 5-MNP-85 Pact 12 0f 15 1 ' 1 (Cardiac Catheterization Continued) 2. A ro riate Len th of Has ital Sta for an Uncom licated PP P g P Y _ P Cardiac Catheterization or Angiography The maximum length of hospital stay for an uncomplicated cardiac catheterization or angiography is two nights and three days . VI ECHOCARDIOGRAM DESCRIPTION: An echocardiogrsm is a non-invasive ultrasound imaging procedure of the heart . POLICY: A combined two-dimensional ( 2-D) and M-mode echocardiogram is the format of choice for most echocardiographic examinations. Both 2-D and Recode echocardiograms should be done at the same time and should be considered integral parts of a single examination. 1. Indications for 2-D Echocardioaram An initial 2-D echocardiogram may be indicated in patients with suspected or known heart disease for the noninvasive evaluation of cardiovascular anatomy and function and documentation ot structural or runcc~ona~ aerangemen~s. _ . _ . ~ ~ ~ Chances in clinical or cardiac status may be an indication for a repeat study. In a stable patient with heart disease, repeat 2-D echocardiograms may be indicated if there is a change in clinical status or to monitor suspected subclinical progression of the disease that may require a change in clinical management. Repeat echocardiograms to monitor subclinical progression of the disease are not indicated more of ten than once a year . 2 . Indicat ions for Recode Echocardiogram The indications for Decode echocardiogram are the same as those for a 2-D examination, both for initial and repeat studies . However, M-mode echocardiogram alone Is ~na~cacea only if equipment to perform a 2-D echocardiogrsm is not ava i lab le . REVISION NO. REVISION DA" Date of Issue: 2-1-85

Technology Evaluation and Coverage Program Blue Cross and Blue Shield Association Technology Management Department 676 North St. CIair Street Chicago, TE 60611 (312) 440 5529 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X X Ethical/Legal/ Socla Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded A p plication of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods X Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $350,000* * This amount represents the Association's expenditures for technology policy, coding, and related activities. Included are significant portions devoted to imple- menting the Technology Evaluation and Coverage Program and the Medical Ne- cessity Program. TECHNOLOGY EVALUATION AND COVERAGE PROGRAM BLUE CROSS AND BLUE SHIELD ASSOCIATION Introduction The Technology Evaluation and Coverage Program of the Blue Cross and Blue Shield Association develops medical policies for the Association's Uniform Medical Policy Man- 319 ual. Uniform Medical Policies are provided to Blue Cross and Blue Shield plans primarily for advisory purposes; however, their imple- mentation is stipulated for certain national account contracts. National account con- tracts generally are made with large corpora- tions, such as General Motors and AT&T, that operate in more. than one state or region and are served by more than one local Blue Cross or Blue Shield plan. In these cases, a

320 model Matrix Contract for national accounts may be adopted so as to provide uniform ben- efits to a corporation's beneficiaries. As agreed to in such a contract, the administra- tion of these benefits is subject to the Uni- form Medical Policy Manual, as revised. monitoring Purpose The purpose of the Technology Evaluation and Coverage Program (TEC) is to help the Blue Cross and Blue Shield plans fulfill their responsibility to uniformly pay for care of good quality at reasonable cost. The role of the Association in evaluating technologies is primarily advisory. The program is intended to help plans to deal quickly and equitably with specific questions of efficacy and cover- age. While Association advice is often ac- cepted, plans generally make their own de- terminations. Subjects of Assessment TEC primarily assesses medical and surgi- cal procedures which relate directly to issues of coverage. Drugs and medical devices gen- erally are evaluated insofar as they are em- bodied in procedures and billed as such, e. g., in the case of surgery to implant a particular device. In a few cases, support systems have been evaluated, e.g., ambulance services. New diagnostic procedures are given particu- lar scrutiny. TEC addressed 90 issues in 1983 and 63 issues in 1984. The following are ex- amples of issues addressed in 1984. i] n vitro fertilization magnetic resonance imaging major organ transplants medical foods amino acid based foods extraoperative electrocorticography local hyperthermia intraoperative sensory evoked potentials (SEP) · portable nocturnal hypoglycemia detec- tors automatic implantable defibrillators automatic external defibrillators suction assisted lipectomy bone marrow transplants · diagnostic endocardial electrical record- ing and stimulation ASSESSING MEDICAL TECHNOLOGY · neutron beam therapy · proton beam therapy · percutaneous translum in al angioplasty · biofeedback · sudden infant death syndrome (SIDS) - · physician assistants · ambulance services Stage of Diffusion TEC is primarily concerned with new and emerging technologies and with certain exist- ing technologies that are not in widespread use. Determining a technology's level of de- velopment is one of the program's concerns, as described below. Concerns The main concerns of TEC are the safety and effectiveness of technologies, and their level of development. TEC has recently be- gun to consider the cost-effectiveness of a few technologies. Most Blue Cross and Blue Shield plan contracts, including the national account contracts, exclude benefit payments for technologies which are termed experi- mental or investigative. Uniform Medical Policies are used in administering such con- tract exclusions. Thus TEC is concerned with determining whether technologies are experi- mental, investigative, or standard, and if ap- propriate, identifying clinical indications for their use. Experimental technologies are those that have been largely confined to labo- ratory and/or animal research. Investigative technologies are those that have progressed to limited human applications but lack wide recognition as proven and effective proce- dures in clinical medicine. Standard technol- ogies are those that are widely accepted as clinically effective procedures; however, such technologies may need to be qualified as standard only under certain specified cir- cumstances. TEC increasingly seeks information from medical societies and the medical literature documenting the safety and effectiveness of technologies. TEC may also provide plans with information regarding coverage matters that should be considered when determining

APPENDIX A: PROFILES reimbursement, such as costs of acquisition, facilities, training, and depreciation. Requests Topics for assessment originate through the claims process. Most, though not all, new procedures are first seen by the plans through claims from individual practitioners. Because of contract variations, state-legislated man- dates, and local practice variations, inquiries regarding local Blue Cross and Blue Shield policy normally are directed first to the indi- vidual plans. Increasingly, inquiries about the coverage of procedures and particular medical products are being made prior to claims submission, as the system is better known. Association staff work with plans on a day-to-day basis in responding to inquiries regarding medical policies and related mat- ters. Selection The need for involvement of the Associa- tion is determined by plans' ability to resolve coverage matters locally. Before considering coverage for drug- or device-embodied pro- cedures, plans generally require that the drug or medical device have FDA premarket ap- proval, though FDA approval is not suffi- cient for plan coverage. Likewise, although HCFA decisions are carefully considered by the plans, HCFA approval of a technology as "reasonable and necessary" for Medicare beneficiaries is not sufficient for plan cover- age. A claim for an unrecognized procedure will be forwarded to the medical director of the receiving plan. Medical directors have varying resources for resolving claims. At California Blue Shield, for example, there is a Medical Policy Committee representing most specialties and the research establish- ment. If the medical staff of the plan is un- able to dispose of the procedure, the Medical Policy Committee will be called upon for ad- vice. Blue Shield of Massachusetts convenes an Interdisciplinary Medical Advisory Com- mittee to assist it in making coverage deci- sions for new technologies. Other plans may conduct their own assessments or surveys of 321 available information on new technologies. The many plans that serve as Medicare fiscal intermediaries (i.e., administer Medicare claims for HCFA) may closely observe or par- ticipate in the HCFA assessment process. Process If a claim is not resolved locally, it may be referred to the Blue Cross and Blue Shield As- sociation. The Association's response may consist of advice to the inquiring plan, advice to all plans, or development of a Uniform Medical Policy or a new procedure code. Upon receiving a request from the plan, the Association will first attempt to deter- mine if the procedure is really new, since "new" procedures may simply be minor vari- ations of existing procedures. If the variation is not significant for the purposes of reim- bursement, the plan will be advised to code the procedure as the recognized procedure. This has the advantage of minimizing fragmentation, and of using established data bases for pricing and utilization review. If the procedure appears to be new, the As- sociation will poll plans to determine if any have dealt with it. If the issue has already been resolved by one or more plans, and if the resolution appears to be reasonable, the in- formation will simply be transmitted to the requesting plan. If the issue has not been re- solved among polled plans, inquiry may be made to yet other plans, HCFA, or the Office of CHAMPUS. If the issue remains unresolved, TEC staff gathers information on the issue from a num- ber of other sources. Staff may conduct a lit- erature search and may seek opinions from among the Association's registry of consul- tants in various specialties. In addition, the staff may contact appropriate medical spe- cialty organizations for any experience in ad- dressing the issue. The Association does not conduct original clinical research to deter- mine clinical efficacy and indications. Infor- mation derived from the literature search and consultation is forwarded to the Associa- tion's Medical Advisory Panel. This panel, which generally meets quarterly, considers the available information in an interactive though not formalized group setting.

322 Depending upon the issue, the panel may circulate its draft findings to all or a sample of plan medical directors for comment before reaching a final opinion. The Medical Advisory Panel has several possible courses. It may simply issue advisory opinions to plans. Advice to plans may consist of noting a technology's stage of development and level of acceptance; recommendations or guidelines clarifying technical and clinical details regarding safety, effectiveness, or ap- propriate use; and important issues for plans to consider in their coverage decisions. When formulating advice on new technologies, the Association may consider cost-effectiveness information. This information does not af- fect the recommendations directly, but is transmitted to the plans. The Association does not recommend an amount for reim- bursement. However, as noted above, it may provide information which plans may use in determining appropriate reimbursement. Plans are free to weigh the information in their respective coverage policy decisions. The Medical Advisory Panel may also elect to assign a code to the procedure. This code establishes the procedure's identity for pur- poses of reimbursement and utilization re- view. Ordinarily, new codes will be assigned only where significant differences from exist- ing technology are perceived. Frequently, the Association incorporates its recommendations in the Blue Cross and Blue Shield Uniform Medical Policy Manual. This manual became effective January 1982 and governs the administration of contracts in which it is incorporated, as described above. Of the issues reviewed by the Medical Advisory Panel, approximately one-half be- come Uniform Medical Policy. The panel reports its recommendations to Association staff, and for selected issues, to the Association's committees and board. A separate but entirely parallel process is used for the assessment of dental technology, in- volving a Dental Advisory Panel. Assessors The Medical Advisory Panel consists of about 10 members and is selected by the se- nior staff of the Association. Most members ASSESSING MEDICAL TECHNOLOGY are plan medical directors, primarily of the larger plans, and represent a mixture of spe- cialties, geographic locations, and back- grounds in clinical practice, academe, and administration. Turnaround The length of time required to review an issue varies considerably. Some issues can be resolved by TEC staff within 48 hours. Uni- form Medical Policies generally require about 6 months to be made final, and most issues are disposed of within 1 year. Factors influencing turnaround include the complex- ity of the issue and whether it is necessary to seek the clinical opinions of medical specialty . ~ socletles. Reporting The dissemination of information varies. Medical policy advice and information is transmitted directly to plans by the Associa- tion's TEC Newsletter and various plan bul- letins. Uniform Medical Policies are trans- mitted as inserts to the Uniform Medical Policy Manual. The information is normally presented as medical policy which includes the following components: 1. applicable procedure coders); 2. brief description of the technology; 3. status of service, i.e., experimental, in- vestigative, or standard (generally accepted) practice; 4. the specific clinical indications which apply to the coverage of services (if appropri- ate); and 5. further policy considerations, excep- tions. Impact In addition to those plans that are obliged to comply with Uniform Medical Policies as per their national account contracts, most other plans voluntarily adopt the Uniform Medical Policies in the administration of lo- cal accounts. However, the Association does not track changes in reimbursement patterns

APPENDIX A: PROFILES that may have resulted from the implementa- tion of Uniform Medical Policies. Reassessment Uniform Medical Policies are reviewed at least every 2 years to determine if revisions are necessary. Existing policies may be reas- sessed sooner if it is apparent that new evi- dence exists and clinical opinions have changed sufficiently to warrant a revised pol- icy, e.g., the reassessment of chemonucleoly- sis following FDA approval of chymopapain. Funding/Budget The Association offers this technical assis- tance as part of its ongoing support to plans. The Association does not charge plans a user fee. In its annual budget the Association de- votes approximately $350,000 to technology management and coding, and related activi- ties, with significant portions devoted to im- plementing TEC and the Medical Necessity Program. Example On the following pages are Uniform Medi- cal Policies on sensory evoked potential (SEP) 323 response studies (revised December 1984) and chemonucleolysis (revised December 1984~. Sources Blue Cross and Blue Shield Association. Uniform Medical Policy Manual. Sensory Evoked Potential (SEP) Response Studies. Section I. Page 92280.0-2. Revised December 1984. Blue Cross and Blue Shield Association. Uniform Medical Policy Manual. Chemonucleolysis. Section III. Page 62292.0. Revised December 1984. Gleeson, S., Executive Director, Technology Man- agement, Blue Cross and Blue Shield Association. 1985. Personal communications. Morris, L. C., Senior Vice President, Health Bene- fits Management, Blue Cross and Blue Shield Associa- tion. 1985. Personal communications. Office of Technology Assessment. 1984. Health Technology Case Study 27: Nuclear Magnetic Reso- nance Imaging: A Clinical, Industrial, and Policy Analysis (Chapter 8: Third Party Payment Policies). Washington, D.C.: U.S. Government Printing Of- fice. Tennenbaum, D., Manager, Medical Necessity Program, Blue Cross and Blue Shield Association. 1985. Personal communications. Assistance was also provided by K. Smith, Manager, Technology Evalua- tion and Coverage Program, Blue Cross and Blue Shield Association.

324 ASSESSING MEDICAL TECHNOLOGY UNIFORM MEDICAL POLICY MANUAL SUBJECT SENSORY EVOKED POTENTIAL (SEP) RESPONSE STUDIES SECTION T PAGE 92280.0 PROCEDURE CODE RANGE DESCRIPTION POLICY 92280 92585 95925 A noninvasive* technique in which e- voked responses are measured and re- corded through electrodes, and averaged by computer. An assessment is then made of the integrity of specific necrologic and auditory functions. * * The following three types of EVOKED RE- SPONSE STUDIES are generally accepted ** medical practice*: * * 1. VISUALLY EVOKED POTENTIAL (VEP) RE- .* SPONSE STUDY This procedure is considered gener- ally accepted medical practice in detecting delays in the conduction of the visual pathways as may re- sult from the demyelination pro- cess, especially as they relate to: o detection of possible multiple sclerosis; 0 monitoring changes related to treatment or spontaneous re- mission of the disease pro- cees; and 0 establishing past visual in- volvement in suspected eul- CONTINUED REVISION SOMBER 6 REVISION DATE 12/84

APPENDIX A. PROFILES UNIFORM MEDICAL POLICY MANUAL . 325 SUBJECT SENSORY EVOKED POTTY IAL ( SEP ) RESPONSE STUDIES SECTION I PAGE 92280. ~ tiple sclerosis patients who have no visual problems at the present. 2. BRAINSTEM AUDITORY EVOKED RESPONSE ( BAER/BSER ) STUDY: This procedure i. considered gener- ally accepted medical practice* when used for the following: o to differentiate metabolic from structural lesions of the brainstem and to define the location and nature of the latter; o to localize brainstem tumors, particularly those which can not be revealed by CT acan- ning; o to assess recovery of function id cases of brainstem lesions due to demyelination or trau- ma. Such potentially irre- versible lesions include multiple sclerosis, central pontine myelinolysis, brain- stem contusions, vertebrobasi- lar insufficiency, postremov- al of apace occupying lesions compressing the brainstem; o to supplement the BEG in eval- uating the irreversibility of coma or "brain death"; and 0 to measure the type and extent of hearing impairment and to determine the degree of neural maturation in children and ne- onates. CONTINUED REVISION DUMBER 5 REVISION DATE 12/84

326 ASSESSING MEDICAL TECHNOLOGY UNIFORM MEDICAL POLICY MANUAL . SUBJECT SENSORY EVOKED POTENTIAL (SEP) RESPONSE STuvIES SECTION ~ PAGE 92280.2 3. SOMATOSENSORY EVOKED POTENTIAL ** (SSEP) RESPONSE STUDY (CEREBRAL EVOKED POTENTIALS) This procedure is considered gener- ally accepted medical practices in evaluating the following: o spinal card injuries; o severe head injuries; and o specific necrologic deficits. EFFECTIVE DATE EXCEPTIONS DESCRIPTION POLICY EFFECTIVE DATE 7/82 6/83 Reevaluated 6/84 Reevaluated INTRAOPERATIVE SENSORY EVOKED POTENTIAL (SEP) MONITORING Noninvasive* monitoring techniques used during surgery to assess the neurologi- cal function of the anesthetized patient or to minimize postoperative morbidity. The INTRAOPERATIVE use o f SENSORY E- VOKED POTENTIALS (SEP) is EXPERIMENTAL/ INVESTIGATIVE*, including: 1. 1/85 visually evoked potentials; brainstem auditory evoked response; somatosenaory evoked potentials (SSEP) during spinal and orthopedic surgery; and SEP monitoring of the sciatic nerve during total hip replacement. REVISION NUMBER 5 REVISION DATE 12/84 * * * *

APPENDIX A: PROFILES UNIFORM MEDICAL POLICY MANUAL SUBJECT CHEMONUCLEOLYSIS SECTION III PAGE 62292.0 PROCEDURE CODE DESCRIPTION POLICY EFFECTIVE DATE POLICY CONSIDERATIONS 327 62292 Chymopapain, a proteolytic enzyme, is injected into a herniated disc to cause breakdown of the chondromucoprotein within the disc. CHEMONUCLEOLYSIS utilizing chymopapain (Chymodiactin) is generally accepted medical practice* only for herniated intervertebral lumbar discs unresponsive to conservative treatment. d/81 3/83 Reevaluated 6/84 Reevaluated CHEMONUCLEOLYSIS te approximately one- half, or fifty percent as difficult as a laminectomy, or approximately three times as difficult as a discogr~m. * * * * A discogram is an integral part of CHEM- ONUCLEOLYSIS. When a radiologist per- *e forms the discogram, his efforts consti- tute approximately one-third of the CHEMONUCLEOLYSIS procedure. REVISION NUMBER 5 REVISION DATE 12/84 * * * * * * * *

ECRI 5200 Butler Pike Plymouth Meeting, PA 19462 (215) 825 6000 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/ Cost-Effect/ Effectiveness Cost-Benefit X X . X X Ethical/Legal/ S., octal Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X X X Stage of Technologies Assessed X Emerging/new X Accepted use X Possibly obsolete, outmoded A p plication of Technologies X Prevention X Diagnosis/screening X Treatment X Rehabilitation Assessment Methods X Laboratory testing X Clinical trials X Epidemiological and other observational methods X Cost analyses X Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $5,000,000 ECRI Introduction ECRI (formerly the Emergency Care Re- search Institute) is an independent, nonprofit corporation that evaluates and assesses medi- cal devices and equipment. ECRI also pro- vides publication, information, education, and consultation services to assist hospitals, health care professionals, and governmental and voluntary sector agencies in improving the safety, efficacy, and cost-effectiveness of health care technologies. This discussion of ECRI evaluation activi- ties is devoted primarily to the Health De- vices Program (ECRI/HDP), an evaluation 328 and information dissemination service pro- vided to over 2,500 member hospitals. Mem- ber hospitals receive comparative medical device evaluations conducted by ECRI and published in the ECRI journal Health De- vices, which is similar in purpose and format to the popular Consumer Reports. ECRI pro- vides other publications addressing medical devices, hospital risk control, and related is- sues, which are described below under Re- porting. In addition to its Health Devices Program, ECRI provides a wide variety of technology- related consulting services to health care facilities, including assistance with codes, standards and accreditation, equipment

APPENDIX A: PROFILES planning, acquisition and testing, chemical and gas monitoring, accident investigation, and risk control services. In a program initi- ated in 1984, an interdisciplinary staff of an- alysts conducts comprehensive assessments focusing on diagnostic imaging and clinical laboratory technologies for publication in ECRI's new peer-reviewed Journal of Health Care Technology: Assessment, Planning, and Value Analysis. The National Implant Registry is a pilot program established as a nonprofit organiza- tion by ECRI. This registry maintains a per- petual, central record of medical device im- plants (e. g., pacemakers and prostheses such as heart valves and artificial hip joints) and patients, and automatically notifies hospitals and physicians of implant recalls or deficien- cies, identifying patients and addresses when action may be indicated. The National Im- plant Registry is supported primarily by member hospitals and physicians. Purpose The purpose of ECRI is to assist hospitals, health care professionals, and governmental and voluntary sector agencies in improving the safety, efficacy, and cost-effectiveness of health care technologies. In particular, the purposes of ECRI/HDP are to 1. conduct assessments of medical devices Requests and other technologies 2. provide independent, objective judg- ment for selection, purchase, and use of med- ical instruments, equipment, and systems 3. function as a clearinghouse and investi- gate and resolve hazards and deficiencies in medical devices 4. encourage the improvement of medical devices through an informed marketplace Subjects of Assessment ECRI/HDP evaluates many types of diag- nostic and therapeutic medical devices, equipment, and support systems, as well as some preventive and rehabilitative technolo- gies. These range from disposables such as hypodermic syringes and nasal oxygen can- nulas to electric beds, x-ray units, and patient 329 monitoring systems. Comparative evalua- tions are usually conducted within a product category. Table A-6 shows technologies eval- uated in the journals Health Devices and the new Journal of Health Care Technology. Stage of Diffusion ECRI/HDP evaluates new and existing technologies that are being actively marketed by industry and purchased by hospitals. Some technologies may be evaluated as obso- lete or outmoded. Concerns ECRI/HDP conducts comparative evalua- tions of the efficacy, performance, safety, ease of use, and cost-effectiveness of technol- ogies. The comparative evaluations are used to provide brand name ratings of specific products. In addition to these concerns, the publication Issues in Health Care Technol- ogy addresses legal, ethical, economic, and social issues of medical technologies; and the publication Health Devices Alerts provides weekly notification of hazardous devices and recommendations that require corrective action. Topics for ECRI/HDP evaluation are staff initiated or originate from inquiries made to ECRI by hospital members of the Health De- vices Program that are considering technolo- gies for purchase. These inquiries provide indications to ECRI that its hospital member- ship may be especially interested in evaluative information for certain product categories. ECRI operates two formal networks to handle requests, inquiries, and reports of user experience. The Problem Reporting Net- work receives reports of adverse experiences with medical devices from hospitals, health professionals, government agencies, and manufacturers, and reviews and abstracts the relevant clinical, engineering, and legal literature. These reports are evaluated by ECRI engineers and, when appropriate, are reported in ECRI/HDP publications to in-

330 TABLE A-6 Evaluations Published in Health Devices, 1981-1985,and.70urnal of Health Care Technology, 1984-1985 Health Devices (volume:page) Anesthesia unit gas scavengers (12:267) Arrhythmia monitoring systems (11:211) Batteries, medical device (14:209) Blood gas/pH analyzers (12:59) Blood warmers (13:191) Breathing circuits (12: 183) Defibrillators, line-powered (12:291) Disposable pressure transducers (13:268) Electrocardiographs, three-channel (13:235) Electrode monitoring systems, electrosurg~cal, return (14: 115) Electronic intermittent thermometers (12:3) Electrosurg~cal electrodes, active, hand-switched (11:69) Enteral feeding pumps (14:9) Ethylene oxide sterilizers (11:287) External transcutaneous pacemakers, Pace*Aid Model 50C (13:3) Fetal monitors (11: 123) Heat and moisture exchangers (12: 108) Incontinent pads (12:108) Infant incubators (11 :47) Infant radiant warmers (13:119) Infant transport incubators (11: 179) Infusion controllers (11:75; 14:219) Infusion pumps (13:31) Operating room ECG monitors (11:155) Oxygen analyzers (12:183) Oxygen monitors, transcutaneous (12:213) Patient bed scales (13:75) Physiologic monitoring systems ~ 1 1:2 1 1; 1 4: 1 43) Pneumatic tourniquets (13:299) Suction canisters (12:127) Surgical case carts (11:311) Surgical gloves (12:83) Volume ventilators (11 :264) Wall vacuum regulators (14:191) X-ray film processors (11:99) Journal of Health Care Technology (volume:page) Automated leukocyte differential counters (2:51) Automated microbiology systems (1 :213) Deaths during general anesthesia (1:155) Digital imaging storage and retrieval (1: 13) Digital subtraction angiography (DSA) (1:177) Freestanding imaging centers (1:257) Magnetic resonance imaging (MRI) (2:23) Therapeutic apheresis (1:279) Therapeutic drug monitoring (TDM) (1 :39) ASSESSING MEDICAL TECHNOLOGY form users of the problems and recom- mended solutions. A number of ECRI's sources of information about medical devices have been consolidated into the User Experi- ence Network, a data base of user experience with specific device brands and models. It in- cludes reports from the Problem Reporting Network, results of regular surveys and ques- tionnaires directed to device users, and inter- views about user experience that are a regu- lar part of ECRI/McGraw-Hill Product Comparison Systems (a series of information services about specialized technologies). Other reports are based on ECRI's extensive accident investigation and forensic engineer- ing studies. Reports derived from the User Experience Network appear in ECRI publi- cations and electronic data bases (e.g., Na- tional Clinical Engineering Computer Net- work). Approximately 40,000 reports were on ECRI's computer data base as of January 1985. To avoid conflict of interest, neither ECRI nor its staff members provide medical device evaluation services to inventors, manufactur- ers, or distributors of medical devices, or ac- cept financial support from these parties. Selection Topics for evaluations are selected based on the volume of inquiries from ECRI/HDP member hospitals and the experience of ECRI's senior staff about their importance to hospitals and to safe, efficacious, and cost- effective patient care. Process The comparative evaluations conducted by ECRI/HDP and reported in Health De- vices are based on ECRI laboratory, clinical, and field (i.e., in-hospital) evaluations. Lab- oratory evaluations are conducted in ECRI's 45,000-square-foot facility, and clinical stud- ies (in vivo evaluations of device perfor- mance) are conducted in selected member hospitals. Evaluations follow appropriately reviewed medical/scientific protocols devel- oped by ECRI for device evaluation.

APPENDIX A: PROFILES Assessors Evaluations are conducted by ECRI's full- time interdisciplinary staff of more than 120, representing medical, engineering, and ana- lytical sciences. There is an extensive review process involving both in-house and indepen- dent reviewers, typically including clinicians with special expertise in the subject area. No staff member may consult for or own stock in medical device companies. Turnaround The usual time between the selection of an evaluation topic and the publication of the evaluation in Health Devices is 6 to 9 months. Reporting ECRI has 15 publications addressing med- ical device evaluation, hospital risk control, and related issues. Three of these publica- tions are included in the ECRI/HDP: Health Devices, Health Devices Alerts, and Issues in Health Care Technology. · Health Devices is published monthly by ECRI. In addition to comparative evalua- tions, Health Devices includes editorials and hazard reports of deficiencies and hazards re- ported to ECRI by equipment users and manufacturers. (Manufacturers are made aware of hazard reports related to their equipment as soon as deficiencies are found, and they are invited to respond.) Approxi- mately 170 comparative evaluations have been published in Health Devices since 1973. Subscriptions to Health Devices are available only through membership in the ECRI/HDP. · Health Devices Alerts is a weekly ab- stracting service which summarizes articles, letters, recalls, and problems with medical devices from the medical, engineering, and legal literature, calling out action items that require immediate response. · Issues in Health Care Technology is a bi- monthly publication provided in loose-leaf form which addresses emerging technologies, economics, ethics, reimbursement, and gov- ernment regulations and policies. The "New Technology Briefs" section of this publication 331 contains miniassessments of a broad range of new clinical technologies. Members of ECRI/HDP receive a full vol- ume of 12 issues of Health Devices, 52 issues of Health Devices Alerts, and 6 mailings of Issues in Health Care Technology annually, in addition to telephone consultation and other services. In 1985, an annual member- ship in the Health Devices Program cost $875, and single copies of Health Devices cost $50. Additional ECRI publications include the following: · Technology for Health Care is a set of monthly specialty newsletters on anesthesia, cardiology, emergency medicine, materials management, respiratory therapy, and sur- gery. · Health Devices Sourcebook is an annual directory of 6,000 categories of medical de- vices, equipment, and manufacturers, based on a continually updated computerized data base. It provides a widely used standard no- menclature and computer coding. · Hospital Risk Control is a four-volume, loose-leaf, monthly publication on issues of hospital risk management. · journal of Health Care Technology is a journal begun in 1984 that includes assess- ments performed by ECRI staff on clinical laboratory and radiography/imaging tech- nologies, and submitted papers on a broad range of health technology issues. Because ECRI depends on publication rev- enue to support its assessment activities and the policy of the National Library of Medi- cine (NLM) is to index only those publica- tions that they may freely reproduce, ECRI publications are not included in NLM in- dexes. However, indexes and data base searches are available from ECRI. ECRI has three technology comparison services in loose-leaf binder formats mar- keted by McGraw-Hill. These address the se- lection and purchase of capital equipment for hospitals, clinical laboratory equipment and supplies, and diagnostic imaging and radiol- ogy products. Other information services in similar formats for surgery, emergency medi- cine, anesthesia-critical care, materials man-

332 agement, supplies and disposables, and home health care products will be introduced in the near future. Impact ECRI provides the Health Devices Pro- gram to over 2,500 member hospitals, repre- senting about 70 percent of all acute-care hospital beds in the United States. (Many Ca- nadian hospitals and overseas health care or- ganizations also are members.) The Health Devices Program membership renewal rate has exceeded 95 percent since its inception. Periodic surveys of Health Devices Pro- gram members have indicated a high degree of satisfaction with the program. According to ECRI, a majority of the hospital CEOs reading Issues in Health Care Technology rated it as more useful and valuable than other hospital publications that they read. Insofar as the impact of the Health Devices Program on safety of patient care is con- cerned, numerous specific product improve- ments have been directly attributed to prod- uct evaluations published in Health Devices, thus benefiting all hospitals, not just those that are program members. For instance, ECRI reports that following an extensive 1973 study of electrosurgical machines, most manufacturers undertook major redesign to improve safety. With an estimated 90 per- cent replacement of the U.S. nationwide in- ventory with improved equipment over the past decade, the impact has been significant; many fewer electrosurgical burns are cur- rently reported to ECRI. ECRI attributes cost savings in the hundreds of millions of dollars to ECRI/HDP evaluations and other technology-related efforts on behalf of mem- ber hospitals (e.g., the National Electrical Code controversy over isolated power re- quirements in anesthetizing locations). Reassessment Product categories are reassessed based upon member hospital inquiries for more ASSESSING MEDICAL TECHNOLOGY current information than is available from previous evaluations. These normally occur when a significant number of new product models appear on the market in a given prod- uct category. Funding/Budget The 1985 budget for ECRI's total technol- ogy assessment activities is approximately $5.0 million. ECRI is supported through earned income, grants, and contributions. Most of its operating budget comes from pub- lication sales, information program member- ship, and fees from consulting, laboratory, and technical services. ECRI does not accept financial support from inventors, manufac- turers, or distributors of medical devices. Example The following is the first page of an ECRI comparative evaluation of critical care venti- lators published in Health Devices (August 1982, Vol. 11, No. 10) and is reproduced with permission here. Due to its length (20 pages) and copyright limitations, the balance is not included here. Sources ECRI. 1982. Critical care ventilators. Health De- vices 11:264-283. ECRI. 1983. ECRI: Information and Consultation Services for the Health Community. Plymouth Meet- ing, Pa. ECRI. Undated. National Implant Registry. Plym- outh Meeting, Pa. Mosenkis, R., Vice President, Publications, ECRI. 1984. Personal communications. Nobel, J., President, ECRI. 1984. Personal com- munication. VanAntwerp, M., Director of Policy Analysis, ECRI. 1985. Personal communications.

APPENDIX A: PROFILES Evaluation Health Devices Sourcebook 1982~3 Reference Ventilators, Volume [1 4-362] Critical Care Ventilators Positive pressure ventilation is the insufflation of the lungs by the forceful delivery of gas. Although known and practiced for more than a century, the technique was not widely used until the late 1950s, when it superseded negative pressure ventilation. Negative pressure ventila- tors (e.g., the "iron lung," the cuirass shell) were popular because they imitated natural breathing (by exerting negative pressure on the chest as the diaphragm does) but were eventually recognized as less effective, convenient, and versatile than devices that provide positive pressure ventilation. Technical advances in positive pressure ventilation and the ability to quickly and accurately determine the effectiveness of ventilation (through the measurement of arterial blood gases) have allowed rapid development of the modern critical care ventilator. As the figure illustrates, these devices are connected to a source of breathing gases (usually oxygen and ambient or compressed air) and deliver breaths to the patient via an airway, or breathing circuit. Breathing circuits currently used by most ventilators have both inhalation and exhalation lines. [The breathing circuit may also include accessories, such as a humidifier and a nebulizer.] During inhalation, the exhalation valve must remain closed to prevent loss of gases intended for the l SUMMARY We evaluated six critical care ventilators. Five are equipped to deliver PEEP and IMV; the sixth unit is not equipped for these functions and, therefore, Is not appropriate for use on patients with complex respira- tory problems. Most of the units exhibit an improve ment over critical care ventilators of the past In that they detect various kinds of disconnects; the one exception is rated Conditlonally Acceptable. Another unit was rated Conditlonally Acceptable because Its breathing circuit may be occluded when electrical power fails. On the cover: The evaluated ventilators (from left): the Puritan-Bennett MA- 1 and MA 2+2, the Monaghan 225/ SIMV, the Siemens-Elema 900C and 900B, and the Bourns BEAR 1. 333 VENTILATOR/BREATHING CIRCUIT 1 , 1 CONTROLS 1 GAS suPPLy 1 INHALATION ~ ' 1 Jim I PATIENT \ EXHALATION 1 ` VALV E ~ |EXHALATION I EXHAI .ATION PORT Typical Ventilator System patient. The valve opens to permit the exhaled breath to exit through the exhalation port until the airway pressure Was been reduced to the desired level. The ventilator provides direct control of the patient's ventilation variables (see A Primer on Ventilation, p. 265), as well as other variables (e.g., the concentration of inspired oxygen) and the limits on certain variables for safe operation. All these controls allow the clinician to provide better patient management, even for patients with serious respiratory impairments. The ventilator can be adjusted to suit the needs of a particular patient and his current phase of treatment. For example, the ventilator can sense inspiratory efforts of a patient who is regaining his capacity to breathe and immediately deliver an assisting breath. If the mode of treatment or the patient's condition changes, the operating mode of some ventilators can be changed, via panel controls, to provide special functions (e.g., positive end expiratory pressure, or PEEP; see Primer) without requiring the addition or reconnection of various pieces of equipment (e.g., a PEEP valve). The greater the complexity of the ventilator equipped for multiple therapies, the greater the chance for malfunction and operator error (see the table on p. 268, constructed from literature reports of both simple and complex ventilators). Therefore, the devices are equipped to monitor variables such as pressure, exhaled volume, Duplication of HEALTH DEVICES~, in whole or in part, by any moans for ony purpose is illegal.

Hastings Center Institute of Society, Ethics and the Life Sciences 360 Broadway Hastings~on~the Hudson, NY 10706 (914) 478 0500 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/ Cost-Effect/ ErE - =`~ _s MA B=~r . == Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surg~cal Procedures Support Systems Organizational/Admin~strative X X X Stage of Technologies Assessed X Emerging/new Accepted use Possibly obsolete, outmoded Application of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $250,000 HASTINGS CENTER INSTITUTE OF SOCIETY, ETHICS AND THE LIFE SCIENCES Introduction The Hastings Center is a nonprofit corpo- ration formally known as the Institute of So- ciety, Ethics and the Life Sciences. Since its founding in 1969, Hastings has addressed ethical issues arising from advances in health and medicine, the natural sciences, and the social and behavioral sciences. In addition, Hastings conducts studies in natural science, the humanities, behavioral science, and pro- fessional ethics. Other services include an ed- 334 ucational program; fellowships, scholar- ships, and internships; consultation; and publications. The Hastings Center is one of few organi- zations which systematically examines ethi- cal issues arising from medical technologies. Bioethicists at the Kennedy Institute of Eth- ics at Georgetown University are primarily concerned with teaching and individual re- search. The Battelle Institute addresses ethi- cal issues for certain projects, and the Con- gressional Office of Technology Assessment cites ethical, social, and legal issues in certain of its medical technology assessments. The Center has about 9,000 individual

APPENDIX A: PROFILES members, including 1,600 libraries. Mem- bership fees range from $22 for students to $35 for institutions and libraries. Purpose The Hastings Center seeks to carry out nonpartisan research on pressing ethical is- sues; to develop educational programs and literature; and to assist universities, legisla- tors, and professional organizations in coping with moral problems. Subjects of Assessment Technologies assessed have included drug- and medical device-embodied technologies, medical and surgical procedures, and sup- port systems used in screening, diagnosis, and treatment, as well as organizational/adminis- trative technologies. Examples of particular technological areas addressed in Hastings re- search projects have included recombinant DNA research, organ transplantation, prena- tal diagnosis of genetic disease and genetic counseling, human experimentation, life-ex- tending technologies, and health cost-con- tainment policies. Most Hastings Center work is conducted by research groups that address certain tech- nological areas. Among those currently ac- tive are groups on health policy research, chronic illness, neonatology, occupational health, and organ transplantation. Others have been groups on genetics research; ethi- cal, social, and legal issues in genetic counsel- ing and genetic engineering; death and dying; and alternative forms of care for the terminally ill. The death and dying research group, es- Concerns tablished in 1970, has examined the moral, social, and legal issues of the care of the dying engendered by advanced medical technol- ogy. Subjects included organ transplantation and the definition of death, the termination of treatment of dying patients, and the allo- cation of scarce resources to the dying. A suc- cessor group examines the goals of medicine and their relationship to death, suffering, and well-being. It has examined changing so- cial attitudes and practices toward child- birth; the difficulties of treating pain that ap- 335 pears to be psychological in origin; and the nature of suffering in a life-threatening ill- ness, including the role of hospices. The Health Policy Research Group is con- cerned about the quality, cost, and distribu- tion of health care in the United States. This group is studying the ethical issues raised by the increasing rate of technological innova- tion in medicine. By examining technologies already in use such as dialysis and heart transplants and those currently under de- velopment, its members aim to arrive at some consensus that may prove useful to research- ers and policymakers who face difficult deci- sions about the appropriate direction for fi- nancing and distributing new medical technologies. Another study being conducted by the health policy group is addressing the ethical, social, and political problems raised by ef- forts on the part of government to encourage those forms of behavior considered advanta- geous for the preservation of health, and to discourage personal behavior deemed haz- ardous to health. . ... .. . The program on ethical problems of re- search on human subjects monitors govern- ment regulations regarding human subjects research, develops educational and training programs and related activities, and serves as a resource for institutional review boards. Stage of Diffusion Most of the technologies that have been subjects of Hastings assessments have been new and emerging technologies, while some have been widely used technologies. Hastings is concerned with ethical, social, and legal issues of technologies. The Center is especially interested in highlighting the role played by regulatory agencies and commit- tees such as institutional review boards (IRBs) and hospital ethics committees in monitoring new technologies. Requests Subjects for assessments may originate from many sources, including Center staff,

336 fellows of the Center, medical societies and professional organizations, government agencies, foundations, and subscribing mem- bers of the Center. Selection The selection of topics for Hastings proj- ects is generally made by Center staff, as ap- proved by the board of directors. In some cases, final selection is made by foundation approval of project grant proposals made by the Center. Process Hastings works primarily through small, multidisciplinary study groups of about 10- 12 outside specialists. Each group is set up to address a particular set of problems, and may meet four or five times over 12 months or more. Groups usually first meet for informal planning in response to staff suggestions. Work plans are finalized and approved by groups, then approved by the Center director or associate director. Groups often discuss relevant case studies or case histories, and may use a consensus development format. Reports and guidelines go through numerous drafts by Center staff and subgroups. In ad- dition to the study group, Hastings conducts other activities related to technology assess- ment. Staff members have served as consul- tants to state and federal officials and con- gressional committees. Staff members have also served as consultants to organizations such as Blue Cross and Blue Shield of Massa- chusetts, the Massachusetts Hospital Associa- tion, the Battelle Institute, the Congressional Office of Technology Assessment, the Office of Protection from Research Risks at NIH, the President's Commission for the Study of Ethical Problems in Medicine and Biomedi- cal and Behavioral Research, the New York State Department of Health, the Labor Re- sources Committee of the United States Sen- ate, and the House Committee on Science and Technology. Center staff publish papers on ethical issues in medical technology, speak at medical conferences, and respond to inqui- ries from attorneys and journalists. The Hastings education program conducts ASSESSING MEDICAL TECHNOLOGY workshops for teachers and other profession- als throughout the country, and sponsors in- ternships for graduate and undergraduate students and fellowships for visiting scholars. The Hastings Center holds workshops on problems in the ethical and legal assessment of new technologies, e. g., a 1-day workshop held in 1983, "Which Babies Shall Live?," and week-long seminars on medical ethics. Assessors Hastings has a full-time staff of about 23. The research staff members have back- grounds in such disciplines as philosophy, medicine, political science, law, and psy- chology. The multidisciplinary study groups gener- ally include physicians, lawyers, ethicists, and economists. Other participants have come from the fields of literature, history, re- ligious studies, philosophy, and sociology. The selection/appointment of research groups is made by the staff, the director, and the president and occasionally through inqui- ries made to Hastings Center fellows, of which there are currently approximately 150. The Center has a 23-member board of di- rectors comprising persons in medicine, law, ethics, education, industry, and biomedical, social, and behavioral research. New board members are nominated by Center fellows and are approved by the sitting board. Turnaround Turnaround time varies among types of projects. Most studies range from 6 to 12 months, although some have taken 2 years. The Center must also respond quickly to cer- tain types of requests, such as for presenting testimony at congressional hearings and for state and local government agencies. Reporting The bimonthly Hastings Center Report, which reaches an audience of nearly 10,000, is devoted. to case studies, court decisions, and other news and articles regarding ethical problems of the biomedical, behavioral, and

APPENDIX A: PROFILES social sciences and issues in professional and applied ethics. Published since 1971, this is the Center's primary means of communica- tion with its members and the general public. Many of the publication's topics deal with ethical questions arising from the develop- ment of new medical technologies. Articles of the Report are frequently reprinted in books, other journals, newsletters, and for class- room use. IRB: A Review of Human Subjects Re- search has been published since 1979 and ap- pears 10 times a year. Other publications in- clude monographs and books arising out of project work. Also, members of the Center staff act as consultants to communications media and to academia on ethical issues of medical technologies. The Center also offers reading packets for teaching and public information in such cate- gories as ethics and the life sciences; death, dying, and euthanasia; experimentation and informed consent; genetic engineering; and health policy and the allocation of scarce re- sources. The Hasting Center Series in Ethics (pub- lished by Plenum Press) includes books such as Which Babies Shall Live (1985), Ethics, the Social Sciences, and Policy Analysis (1983), In Search of Equity: Health Needs and the Health Care System (1983), Ethics and Hard Times (1983), and Violence and the Politics of Research (1981~. Reassessment The health policy project has reassessed implications of dialysis technologies. Impact Because Hastings does not set policy, it is especially difficult to measure its impact. A 1981 Hastings report listed a variety of activi- ties in which it had participated to indicate both the scope of its work and range of possi- ble impact. Cited were numerous instances of testimony before federal and state legisla- tive committees, over 20 instances of assis- tance to other public bodies, membership on committees and commissions (e.g., NIH con- sensus development conferences), organiza- 337 tion of national conferences, and assistance to a wide variety of public and private associ- ations and societies. Also cited were publica- tion of proposed guidelines on mass screening for genetic diseases, the definition of death and prenatal diagnosis, and participation in drafting legislation on hereditary diseases and the definition of death adopted in a num- ber of states. Over 300 universities and pro- fessional schools have received Hastings Cen- ter assistance in the development of teaching programs in ethics. The New Jersey State at- torney general, concerned about the implica- tions of the Karen Ann Quinlan case in which a young woman became comatose and was being kept alive by life-support sys- tems sought the Center's advice in estab- lishing a definition of death. Funding/Budget The annual budget of the Center is about $1.4 million. Of this amount, about $250,000 is devoted to studies in health and medicine. About 54 percent of Center funding is de- rived from grants (both for specific projects and for the general fund) and contributions from individuals, foundations, and corpora- tions (including drug and medical device companies and insurers); 18 percent is from government agencies (e.g., NIH and the Na- tional Center for Health Services Research); and the remainder is from membership dues, publications, workshops, and other sources. Technology assessment activities are sup- ported directly by foundations such as The Henry I. Kaiser Family Foundation, the Pew Memorial Trust, and the Charles C. Cul- peper Foundation and by general funds from the Hastings Center's budget. The ongoing project on ethical issues of neonatology, for example, is supported by the National Foun- dation-March of Dimes, Squibb, and the Up- john Company, among others. Example On the following pages is the full text of the Hastings Center report "The Care of the Terminally Ill: Mortality and Economics," published in 1983 in the New England lour- nal of Medicine (309:1490-1494) and is re- produced here with permission.

338 Sources Caplan, A. L., Associate Director, Hastings Cen- ter. 1985. Personal communication. Goodman, W. June 18, 1984. Medical Ethics are Fare at Hastings Center Party. New York Times. Hastings Center. 1981. The Hastings Center: Eth- ics in the 80s. ASSESSING MEDICAL TECHNOLOGY Hastings Center. 1983. Financial statements for the year ended December 31, 1982. Otten, A. L. November 23, 1983. As Medicine Ad- vances, Hastings Center Tries to Solve Ethical Issues. Wall Street Journal. SPECIAL ARTICLE THE CARE OF THE TERMINALLY ILL: MORALITY AND ECONOMICS RONALD BAYER, PH.D., DANIEL CALLAHAN, PH.D., JOHN FLETCHER, PH.D.*, THOMAS HODGSON, PH.D.T, BRUCE `JENNINGS, M.A., DAVID MONSEES, PH.D.l, STEVEN SIEVERTS, M.S.§, AND ROBERT VEATCH, PH.D.1T Abstract Are current expenditures on dying patients dis- proportionate, unreasonable, or unjust? Although a review of empirical data reveals that care for the terminally ill is very costly, it is not appropriate to conclude that such ex- penditures represent a morally troubling misallocation of societal resources. Moreover, though efforts to reduce the costs of caring for the dying are not unreasonable, they must be undertaken with great caution. At present, such efforts should concentrate on three basic goals: develop- ment of better criteria for admission to intensive- and T—CURING the past decade, the care of the terminal- (J ly ill has become a topic of sharpened debate. The conditions under which people die, the attitudes and practices of the medical profession toward them, and the ability of dying patients to control or modify the circumstances of their death have attracted wide attention. These concerns raise some exceedingly diffi- cult practical and ethical questions for those who care for the terminally ill. From the Hastings Center, 360 Broadway, Hastings-on-Hudson, NY 10706, where repent requests should be addressed to Dr. Bayer. Supported by a grant from the Health Services Improvement Fund of Blue Cross/Blue Shield of Greater New York. *National Institutes of Health, Bethesda, Md. National Center for Health Statistics, Bethesda, Md. "National Institute of Child Health and Development, Bethesda. Md. §Blue Cross/Blue Shield of Greater New York, New York, N.Y. 11Kennedy Institute of Ethics, Washington, D.C. critical-care units; promotion of patient and family autono- my with regard to decisions to stop or refuse certain kinds of treatment; and promotion of alternative forms of institu- tional care, such as hospice care. The most difficult moral problems will arise when pa- tients and their physicians seek access to therapies judged only marginally useful. There may be conflict be- tween administrators with broad institutional responsibil- ities and clinicians committed to particular patients. (N Engl J Med 1983; 309:1490-4.) Yet, as perplexing as these questions are, they be- come even more complex because of a growing, if ill- defined, economic concern that often lurks just below the surface of recent discussions. Terminal care often involves intensive and expensive treatment, and ques- tions have been raised about its value. Is the cost too high? Is it "wasteful"? Many recoil when such questions are raised. In- deed, a repugnance at the implications of a more "sen- sible," calculating approach to the care of the dying may lead one to repress the problem altogether. We believe, however, that the relation between the eco- nomic and the moral dimensions of care for the termi- nally ill is a subject that can be addressed openly, without embracing a crude calculus that trades life for dollars. It is ultimately neither possible nor desirable simply to ignore matters of costs and economics. If such issues are not brought out into the open, deci- Reprinted from The New England Journal of Medicine 309: 1490- 1494 (December 15), 1983

APPENDIX A: PROFILES signs may be made in a way that is beyond the pale of public scrutiny or accountability and on the basis of criteria that are capricious, unreasonable, or danger- ous. Equally important, only a direct, careful discus- sion of the issues will prevent unexamined economic suppositions from artificially restricting full consider- ation of the moral and clinical aspects of terminal care. The purpose of this paper is to stimulate responsible public discussion of the pertinent moral problems, and to do so by identifying some of the moral, conceptual, economic, and clinical issues that arise in the care of the terminally ill. After reviewing the evidence and attempting to specify the relevant moral consider- ations, we propose some general moral principles that may serve as a prolegomenon to more specific moral rules. We also suggest some strategies of cost contain- ment that may lower expenses, but in ways that are responsible and humane from both a medical and a moral viewpoint. THE COSTS OF CARING FOR THE TERMINALLY ILL: ARE THERE MORAL ISSUES? Is a disproportionate, unreasonable, and unjust amount of money being spent on the care of the termi- nally ill? In essence, that is the moral question that haunts current discussions about the care of dying patients. Since the medical needs of the terminally ill are often more acute than those of most other patients and their care is often more labor- and capital-inten- sive, it should hardly be surprising that such care is very costly. But are the costs disproportionate relative to the needs? Is it unreasonable to allocate expensive care to the terminally ill if that care is therapeutically warranted by reasonable standards of clinical judg- ment? And is it unjust to expend resources on the patients most in need of them rather than on those who will otherwise survive? Furthermore, what does "terminal illness" mean? Though widely used, it is not a standard technical term with clear and precise criteria. The difficulties of prognosis, the occasional surprise recovery, and a combination of aspiration and hope can make such a determination problematic in many cases. No wonder many if not most physicians are often reluctant to de- clare formally that a patient is terminally ill. The label "terminal illness" must therefore be used with caution. For the purpose of this paper, we define it as an illness in which, on the basis of the best avail- able diagnostic criteria and in the light of available therapies, a reasonable estimation can be made pro- spectively and with a high probability that a person will die within a relatively short time. This definition is both specific enough to allow some focused discus- sion and general enough to take into account the diffi- culties of making precise predictions about the trajec- tory of dying. Many of the moral and economic questions with which we are concerned in this paper also pertain to a consideration of the problems in caring for the critical- ly ill i.e., patients with poor prognoses whose death 339 is possible but not highly probable, or those who may die. However, our discussion is restricted to patients for whom it is possible to make a prospective determi- nation of terminal illness i.e., those known to be dying. Despite the importance of this distinction for a care- ful analysis of the moral issues surrounding the care of the dying, empirical research has been primarily retrospective and has tended to focus on the cost of care in the last months of life. Thus, the data available tend to conflate the costs of caring for the terminally ill and the critically ill. Nevertheless, a strong infer- ence can be derived from the literature that the termi- nally ill receive proportionately much more expensive care than do other patients. Two kinds of data based primarily on retrospective analyses are available on the cost of caring for the terminally ill; for conve- nience, they may be called "macrolevel" and "micro- level" data. In 1974 Selma Mushkin estimated that over 20 per cent of all nonpsychiatric hospital and nursing-home expenditures in nongovernment facilities were spent on the care of the terminally ill. i Although only 5 per cent of all Medicare enrollees died in 1967, 22 per cent of all reimbursements from that program were made on their behalf. The 1968 figures are similar,2 and the proportions have remained relatively stable over the years. The Health Care Financing Administration re- ported that the cost of such care ranged from 19 to 22 per cent of all reimbursed Medicare charges from 1974 through 1976. Of course, these data are only suggestive and reflect only the costs of care for patients covered by Medi- care. Nonetheless, they are compatible with other mi- crolevel data that is, with the costs of caring for patients who are terminally ill with cancer and for those who do not survive after treatment in critical- or . . . mtenslve-care units. Scotto and Chiazze found that total hospitalizations and payments for patients with cancer who died with- in the 24-month period of data collection from 1969 to 1970 averaged almost twice those for patients who survived longer than 24 months.3 This ratio of dece- dent-to-survivor costs echoes the average Medicare decedent-to-survivor ratio,2 which is over 2:1. Detsky et al. studied an intensive-care unit and reported that "the care of nonsurvivors involved a significantly higher mean expenditure than did the care of survi- vors...."4 In an earlier study of 17 acute-care hos- pitals, the same researchers stated, "the data indicate that use of resources for dying patients exceeds re- source use for other high-cost patients."5 In a 1970 study of the Surgical Intensive-Care Unit at Massa- chusetts General Hospital, Civetta noted that "over- all, the intensive care costs generated by prolonged utilization of this type of facility seem to be inversely related to the probability of patient survival."6 Some of the possible implications of these data have not gone unnoticed. For example, in his study of the treatment of patients who were acutely ill with cancer,

340 Silverman concluded, "a disproportionate amount of intervention was employed on patients who eventually expired. It seems evident that efforts directed at reduc- ing cost and increasing efficiency must be focused on this high-risk, high-cost, low-yield group."7 However, Detsky and his colleagues have sounded a note of caution: the relations between prognosis, expenditure, and outcome are more complex than can be appreciated when a study focuses only on nonsurvivors of on subsets of patients with the poorest prognosis or the highest costs. Among nonsurvivors, the highest charges were due to caring for patients who were perceived at the time of admis- sion as having the greatest chance of recovery. Among survivors, the highest charges were incurred by those thought to have the least chance of recovery. Patients with unexpected outcomes . . . in- curred the greatest costs.... For the clinician, the problem may seem hopelessly complex. Simple cost-saving solutions, such as withholding resources from the hopelessly ill or earlier transfer of those requiring only anticipatory care, are difficult to apply to an individual patient because prognosis is always uncertain.4 Where does that leave us? The available data do not allow us to conclude that the care is disproportionate, unreasonable, or unjust. Nonetheless, as new medical technologies lengthen the time span between the onset of the terminal phase of an illness and death, and as the number of persons over 65 years of age (the largest age group of terminally ill patients) increases, the cost of care for the terminally ill will surely rise above its present level. Hence, the belief in the need for cost- containment policies in terminal-care medicine will undoubtedly persist and may even gain intensity. An intelligent response to this belief requires a more com- plete and careful discussion of the general moral issues raised by cost-conscious decision making in the care of the terminally ill. DEFINING THE MORAL ISSUES There is no need here to repeat the many moral arguments that have been made to justify different forms of care for the terminally ill than for other pa- tients. Their needs are different, and thus their care should be different not less but different. But can the special features of terminal illness sup- port a moral case that less money should be spent on the care of the dying solely on the grounds that they are known to be dying? Or that more money should be spent on their care solely on the grounds that they are dying? Either general proposition, on its face, is hard to defend. To deny care to the terminally ill solely on the grounds that such care does not return the eco- nomic investment would be to stigmatize the dying as second-class persons, treating them with less than the respect deserved by all patients. The position that the dying have a greater right to economic resources runs the double risk of doing an injustice to other patients and using scarce resources without reflection. The real problem is to determine when and in what way a con- sideration of costs is reasonable either in clinical or administrative decision making, and then to devise acceptable criteria for making cost-conscious deci- s~ons. ASSESSING MEDICAL TECHNOLOGY The central dilemma here arises from the uncertain- ty regarding therapies that are only "marginally use- ful." It is unlikely, at one extreme, that anyone— administrator, clinician, family, or patient would in principle be prepared either to justify diagnostic tests and therapies that promise no benefits whatsoever or to dismiss procedures that hold the possibility of sub- stantial benefits. The important differences of opinion Still focus on the use of marginally useful therapies, which can be defined as those that provide a slight but real contribution (physical or psychological) to the welfare of all or most patients or that make a moder- ately valuable contribution to the welfare of some but not most patients (with no certain foreknowledge of which patients are in the minority that will benefit). Given the wide range of possible variations in the notion of"marginally useful" from physical to psy- chological benefits, from moderate benefits for some to none for others, and so forth it is hardly surprising to discover a elide array of attitudes toward them. For some, a benefit is a benefit, marginal or not. For oth- ers, a pursuit of marginal benefits has to be justified vigorously. What the administrator may view as a pat- tern of unjust or wasteful expenses for statistically minuscule benefits the clinician whose practices are being examined may consider a pattern of justified expenses for a series of individual treatments, each undertaken in the best interests of the particular pa- tient. The potential for conflict between administrators and clinicians is likely to be most pronounced in any attempt on the part of the former to set limits on the availability of diagnostic procedures and therapies. Administrators have obligations that are broader than those that confront clinicians. Whether responsible for the functioning of hospitals, concerned about the fiscal integrity of health-insurance programs, or involved in the planning of health services for a community, ad- ministrators must attempt to balance competing inter- ests. At times, financial constraints will force decisions that are justified in terms of institutional or program survival rather than equity. Not infrequently, admin- istrators at different levels of responsibility will con- front each other with claims about the consequences for patients of efforts to limit health-care expenditures. In the end, the clinician's duty to individual patients may exist in a state of tension with the duties and commitments of the administrator. Given the likeli- hood of conflict, clinicians, patients, and the families of patients will benefit if they have a clear understand- ing of administrative policies, the constraints these policies impose, and the reasons for them. STRATEGIES OF COST CONTROL We believe that the attempt to find ways of reducing the costs of the care given to the dying is a reasonable one, since at least some of the current costs are a con- sequence of practices that are of little value to the patients and may in fact be harmful to their interests. But great caution is necessary in trying to reduce

APPENDIX A: PROFILES costs. Any such attempt cannot begin by assuming, as if demonstrated, that a large-scaLe socioeconomic problem exists or that there is a widespread and irre- sponsible indifference to costs. We believe that at present, cost-containment poli- cies for terminal care should concentrate on three ba- sic goals: developing better criteria for admitting pa- . . . .. . tents to Intensive- or erotica -care units, promoting the autonomy of patients and their families, and pro- . . ~ ~ . . . mot1ng a ternatlve forms ot 1nstltutlona care. Developing Better Criteria for Admission to Intensive and Critical-Care Units Considerable evidence suggests that a prime ingre- dient in the costs of caring for the terminally ill is the high cost associated with intensive- and critical-care units. However, the difficulties of prognosis stand in the way of any simple standards for deciding which patients should not receive such (expensive) care. The Massachusetts General Hospital's patient-classifica- tion system and the Therapeutic Intervention Scoring System represent efforts to address such difficulties.8 9 Our point here is not to recommend these particular approaches, which suffer from a failure to take into account patient and family perspectives, but to under- score the need for further efforts of this kind. Promoting Patient and Family Autonomy A major focus in recent years has been the promo- tion of greater patient and family participation in deci- sion making and the provision of a wider range of options for patients. In the case of the terminally ill, such efforts have centered on their right to withdraw from treatment or to refuse certain kinds of treatment and to have a larger number of choices concerning where they spend the remainder of their lives. If patients and their families had greater decision- making powers, the cost of their care might be re- duced, and their welfare enhanced. Our working as- sumption is that at least some terminally ill patients receive expensive care of a kind they would not, if better informed, desire. Finally, every effort should be made at the policy level to maximize the participation of lay people of eventual patients in decisions to place limits on the kinds of care that will be made available to the termi- nally ill or on the services for the terminally ill that will be reimbursable under insurance plans. Promoting Alternative Forms of Institutional Care The hospice movement stands as the primary sym- bol of efforts to promote alternative institutional forms of care for the dying. Its premises are that many of the terminally ill prefer to die at home or in facilities other than those of a hospital, that more appropriate care may be provided in institutions designed primarily for palliation and caring rather than curing, and that pa- tient autonomy and dignity are enhanced by the exist- ence of alternative institutions among which patients can choose. Enough information has begun to accu- 341 mutate to suggest that for those who seek such care both the dying and their families there are benefits. The terminal illness is made more bearable for the patients, and their families seem to adjust to the ill- ness and to the bereavement afterward with greater psychological strength. Yet, to what extent the hos- pice movement will lead to a decrease in the costs of dying is far less clear. Considerably more experience and data will be necessary to reach any final judg- ment on the long-term economic benefits of hospice care 10-~2 In 1982 the Congress moved to bring hospice care within the framework of Medicare, marking a shift in the reluctance of third-party payers to cover such serv- ices. We believe that though there are some risks to this new course, they ought to be run. No evidence exists to show that the net costs of such coverage will exceed those of hospital care for the dying, nor is there evidence that the extension of coverage will be subject to any special abuse or financial mismanagement. Most important, without a serious and much more widespread effort to test the hospice concept, there will be no way to judge the potential economic savings or the benefits to patients. DEVELOPING GUIDELINES FOR THE FUTURE Despite the existence of some anxiety about the mis- allocation of resources in the care of the dying, there is no solid evidence that the health-care system has reached a "tragic choice situation" requiring painful decisions to withhold medical care. Nonetheless, some tentative steps can certainly be taken to minimize the possibility of a wasteful or inappropriate allocation of resources for the care of the terminally ill. It is prema- ture to propose a detailed set of moral rules for allocat- ing resources to the dying, but it is not premature to suggest some broad guidelines that can at least help focus the issues. The general statements that follow are meant to summarize our analysis and findings and to suggest procedures for the future. The Determination of Terminal Illness Even though it may be difficult in many cases, clini- cians should be prepared to make a determination that an illness is terminal and to propose changes in care when such a determination has been made. Services for Terminally 111 Patients When the consequence of a determination that a patient is terminally ill is to change the nature of services that the patient will receive, the clinician should ensure that no services that can considerably prolong the patient's life or reduce physical or psycho- logical suffering are withheld (unless the patient re- fuses them). In ordering services for the terminally ill, clinicians should request no diagnostic tests that do not promise to provide useful information for patient care. Thera- peutic or rehabilitative services should be proposed only to increase the patient's comfort and the quality

342 of his or her remaining life. Responsiveness to the pa- tient's expressed needs and wishes should remain an important norm. The Settings for Care of the Terminally 111 Policy makers and health planners should acceler- ate current efforts to develop reimbursement plans for the care of dying patients in various settings. At a minimum, all communities should have care available in short-term inpatient hospital facilities, in institu- tional outpatient settings, and in patients' homes or surrogate homes. Services for terminally ill patients in all alternative settings should be planned and managed to meet the special medical, psychological, spiritual, and human- support needs of each patient. The hospice concept provides the ingredients for this kind of care. Families that provide services needed by the terminally ill should receive appropriate support and, when neces- sary, special training. Government and private insurance plans should be designed to encourage voluntary efforts. For example, policies that fail to support training programs for home care should be changed. However, government at all levels should accept the responsibility to ensure that terminally ill patients who lack funds from other sources are given the necessary support through the public welfare system. 1. 2 s. FUTURE RESEARCH NEEDS The lack of good data on the costs of caring for the terminally ill both fuels anxiety about the issue and prevents any useful judgment about whether there is a genuine issue. Despite our skepticism that a serious problem exists, further studies can be helpful. Past efforts to collect good data have been hampered by the difficulties inherent in defining terminal illness, by the 9 fact that the studies have been retrospective, and by the fact that available records typically show only that a patient died, not whether the patient was declared terminally ill at some point and, if so, how he or she was subsequently treated. The need for prospective studies, perhaps even participant-observer investiga- tions, is obvious. Such studies will have to make clear ASSESSING MEDICAL TECHNOLOGY the distinct patterns of care required for patients af- fected by different diseases and the variations in care given to patients in different age groups. The concept of marginally useful therapy also requires further in- . . vest~gat~on. A number of studies under way at present may pro- vide better data on the costs of cancer, catastrophic illness, and terminal illness. Some of the studies bear directly on the costs of terminal illness or illness in the last year of life, whereas others have an indi- rect bearing, in the sense that they focus on the total cost of illness. Much more, however, needs to be done. We are indebted to the following participants in the Hastings Center Project on Terminal Illness: Dorothy Rice, Richard Rettig, Ph.D., David Willis, M.P.H., Ida Martinson, Red., Ph.D., Carol Parkas, Stanley Jones, Charles Goulet, Norman Walter, M.D., and Jerome Yates, M.D. REFERENCES 6. 7. Mushkin So, ed. Consumer incentives for health care. New York: Prodist, 1 974: 1 83-2 1 6. Piro PA, Lutins T. Utilization and reimbursement under Medicare for per- sons who died in 1967 and 1968. Washington, D.C.: Social Security Ad- ministration, 1973. (DHEW publication no. (SSA)74-11702). Scotto J. Chiazze L. Third national cancer survey: hospitalizations and payments to hospitals. Part A: Summary. Bethesda, Md.: National Institutes of Health, 1974. (DHEW publication no. (NIH)76-1094). 4. Detsky AS, Stricker SC, Mulley AG, Thibault GE. Prognosis, survival, and the expenditure of hospital resources for patients in an intensive-care unit. N Engl 1 Med 1981; 305:667-72. Schroeder SA, Showstack JA, Roberts HE. Frequency and clinical descrip- tion of high-cost patients in 17 acute-care hospitals. N Engl J Med 1979; 300: 1 306-9. Civetta IM. The inverse relationship between cost and survival. I Surg Res 1973; 14:26S-9. Silverman W. Goldiner PL, Kaye BA, Howland WS, Turnbull AD. The therapeutic intervention scoring system: an application to acutely ill cancer patients. Crit Care Med 1975; 3:222-5. 8. Optimum care for hopelessly ill patients: a report of the Clinical Care Com- mittee of the Massachusetts General Hospital. N Engl I Med 1976; 295:362- A Cullen Do, Civetta JM, Briggs BA, Ferrara LC. Therapeutic intervention scoring system: a method for quantitative comparison of patient care. Crit Care Med 1974; 2:57-60. 10. Bloom BS, Kissick PD. Home and hospital cost of terminal illness. Med Care 1980; 18:560-4. Kassakian MG, Bailey LR, Rinker M, Stewart CA, Yates IW. The cost and quality of dying: a comparison of home and hospital. Nurse Pract 1979; 4(1):18-23. Comptroller General of the United States. Report to Congress. Hospice care—a growing concept in the United States (March 6, 1979). Washing- ton, D.C.: Government Printing Office, 1979:25. @)Copyright, 1983, by the Massachusetts Medical Society Printed in the U.S.A.

Division of Health Services Research Department of Medical Methods Research The Permanente Medical Group, Inc. 345 ~ Piedmont Avenue Oakland, CA 94611 (415) 428 6700 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effeet/ Effectiveness Cost-Benefit . X X X X X . . X X Ethieal/Legal/ oeial Medical Devices/Equipment/Supplies Medieal/Surg~eal Procedures Support Systems Organizational/Administrative Stage of Technologies Assessed X Emerg~ng/new X Accepted use X Possibly obsolete, outmoded Application of Technologies X Prevention X DiagnosiS/screening X Treatment Rehabilitation Assessment Methods Laboratory testing X Clinical trials X Epidemiologieal and other observational methods X Cost analyses X Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $50,000* * This is the average amount spent for technology assessments since 1979. DEPARTMENT OF MEDICAL METHODS RESEARCH THE PERMANENTE MEDICAL GROUP, INC. DIVISION OF HEALTH SERVICES RESEARCH Introduction The Kaiser-Permanente Medical Care Pro- gram (KPMCP) in Northern California is a group practice prepayment plan providing comprehensive medical and hospital services 343 to about 1.9 million members with 13 hospi- tals, 19 outpatient medical offices, and 1,800 physicians. KPMCP established in 1961 its Department of Medical Methods Research (MMR) for the purpose of conducting health services research directed toward utilizing modern technology for improved delivery of medical care with the KPMCP. MMR is administered professionally by its director under The Permanente Medical Group (TPMG) and has a total staff of about 70 persons. All MMR grants and contracts

344 funded from sources outside KPMCP are ad- ministered by the Kaiser Foundation Re- search Institute, a nonprofit, tax-exempt cor- poration. MMR's main divisions of activity include Epidemiology and Biostatistics, and Health Services Research. The Health Services Re- search Division now includes the activities of the former Technology Assessment Division, which was established in 1979 in response to increased interest of KPMCP in medical and surgical procedures, equipment, and sys- tems. Purpose The primary purpose of the technology as- sessments carried out by the Division of The primary selection criterion for assess- Health Services Research is to aid in the con- ments have been total annual costs. A proce- sideration of alternative choices of technol- dure may be selected for assessment if it has a ogy-based services. low unit cost but a very large case load (e.g., chest x rays) or a large unit cost but a small case load (e.g., renal dialysis). Also selected for assessment have been procedures with in- sufficient information for a decision to in- clude them as Health Plan benefits (e.g., bio- feedback). Studies comparing alternative programs (e.g., multiphasic checkups versus traditional health checkups, primary care by team versus by traditional mode, and com- puter versus manual hospital information systems) have been conducted by the Divi- sion of Health Services Research. ASSESSING MEDICAL TECHNOLOGY Technologies suitable for assessment have been identified within KPMCP at all organi- zational levels; these have included the exec- utive director (for biofeedback), professional service chiefs (alternative treatment modes of end-stage renal disease tESRD]), and pediat- ric geneticists (alpha-fetoprotein screening). The Division also has conducted periodic sur- veys of about 300 KPMCP professional ser- vices chiefs to identify substantial capital- investment equipment needs that might be candidates for assessment. Selection Subjects of Assessment The Division has carried out assessments of procedures, equipment, and systems used in diagnostic, therapeutic, and coordinating patient care services. Stage of Diffusion The Division considers for assessment emerging, new, existing, and potentially out- moded technologies. Concerns The primary concerns of assessments are costs, effectiveness, and the impact on the or- ganization as to technical personnel, equip- ment, facilities, and financing. The assess- ments generally are not made in order to arrive at a single decision or recommenda- tion; rather, they present the important con- sequences intended and unintended of appropriate alternative technologies so that management can make more rational deci- sions; thus the assessments are made to de- crease the uncertainty of decision making. Process Assessments consider the characteristics of the population utilizing the technology, the work loads for its utilization, and its total an- nual costs. Alternative technologies used for the same specified objectives are evaluated as to important intended and unintended conse- quences, with consideration of the alterna- tive competing technologies per million peo- ple. These studies all have used epidemio- logic methods, medical record studies, and literature reviews; consensus development was used for the alpha-fetoprotein study, sensitivity analysis for the ESRD study, and controlled studies for the multiphasic and primary care team studies.

APPENDIX A: PROFILES Assessors Assessments are coordinated by the direc- tor of the Division who works with the proj- ect chief, who assembles a team of 4-10 ex- perts from the KPMCP. Turnaround The average time for an assessment is ap- proximately 6 months. The shortest time to complete an assessment was 3 months for the biofeedback study; the longest was 18 months for the end-stage renal disease study. Reporting In the past 5 years, four assessments have been presented to the executive director of TPMG and its board of directors; these are briefly summarized below under Examples. Impact The TPMG board of directors selected one of the alternatives proposed in the biofeed- back study. The alpha-fetoprotein study was accepted by the board but action was de- ferred pending the State of California's initi- ation of its mandated alpha-fetoprotein screening program. The end-stage renal dis- ease study resulted in the executive director of The Permanente Medical Group appoint- ing a special team to develop a long term plan for ESRD care in the Northern California KPMCP. Reassessment No technology has been reassessed thus far. It is possible that a reassessment of biofeed- back may be requested if new data would become available suggesting improved cost- effectiveness. FundinglBudget Approximately $50,000 per year was ex- pended by the Kaiser-Permanente Depart- ment of Medical Methods Research for tech- nology assessments in the period 1979-1983. The study on utilization of diagnostic x rays 345 was supported in part by the Bureau of Ra- diological Health. Examples Four assessments conducted by MMR (spe- cifically by the former Division of Technol- ogy Assessment) are summarized below. The first, on end-stage renal disease, is discussed in greater detail than the others on biofeed- back, utilization of diagnostic x rays, and se- rum alpha-fetoprotein. A Technology Assessment of Care for End- Stage Renal Disease The purpose of this study was to assess the effects on costs to the Northern California Kaiser Foundation Health Plan (KFHP) of alternative treatment technologies for end-stage renal disease (ESRD) and of various economic and case load factors. ESRD is a unique disease category for KFHP in that it is primarily treated by other than the Permanente Medical Group (TPMG) physicians in outside facilities and Medicare is the primary payer. As a result, KFHP is in a vulnerable financial situation when either Medicare alters its reimburse- ment schedule or when non-TPMG providers use treatment technologies which could be more economically provided by TPMG phy- sicians in Kaiser-Permanente (K-P) facilities. At the beginning of 1982, KFHP was paying in part for the care of 457 ESRD patients (compared to 300 in 1978), and the number of new ESRD cases entering the program for care was about 100 a year. The total pay- ments for care of these ESRD members was estimated to be $12 million, of which Medi- care paid about 65 percent and KFHP paid about 35 percent or roughly $2 per member for the year. For this study, a computer model was em- ployed to generate 5- and 10-year cost projec- tions for 16 scenarios. The model used data from 1978-1981 KFHP experience, and from estimates arrived at by consensus of a group of K-P nephrologists. Due to the uncertainty of both past and future economic data, the study involved a sensitivity analysis in which a variety of assumptions were made for im- portant variables, and cost projections were calculated for each assumption using the

346 computer model. The model used several im- portant variables, including the following: 1. the mix of ESRD technologies used (in- stitutional, center self-care, home care, con- tinuous ambulatory peritoneal dialysis, and kidney transplants from live or cadaver do- nors) 2. the ESRD patient case load 3. the proportion of ESRD patients cared for within K-P facilities 4. the general economic inflation rate 5. the Medicare reimbursement schedule The study recognized that, of these five im- portant variables, K-P can only influence sig- nificantly 1 and 2. The study showed how relatively less sensi- tive are KFHP's total payments to changes in inflation, case load growth rates, and the percentage of patients treated in K-P facili- ties. The study indicated that when KFHP becomes the primary payer, then the cost- effective use of alternative treatments and the care of ESRD patients by TPMG physi- cians will become very important. The sce- narios tested showed that KFHP could pro- tect itself by 1. more aggressive region-wide negotia- tions with non-TPMG providers for lower payment schedules 2. monitoring payments by a centralized computer-based registry 3. lobbying for continuing Medicare sup- port 4. phasing in additional dialysis centers while attempting to decrease internal dialysis costs and initiating programs to employ more lower-cost dialysis treatment modes 5. limiting ESRD benefits to patients cared for by TPMG physicians within K-P fa- cilities The study concluded that it would be pru- dent to consider the probability of a serious decrease in Medicare support of ESRD care by 1986, and K-P could benefit by obtaining more actual in-house experience from estab- lishing pilot programs to develop cost-effec- tive methods for certain modes of treatment. Such action could save KFHP $1 million in 1986 and as much as $18 million over 10 years. ASSESSING MEDICAL TECHNOLOGY Biofeedback A new treatment modality was advocated by some TPMG physicians for chronically recurring headaches and other colons. An assessment was completed us- ing data from three Kaiser-Permanente med- ical centers and from the literature. The con- sequences were assessed as they would relate to three alternative organizational decisions for providing biofeedback as a Health Plan benefit, namely, full biofeedback benefits, partial benefits for treatment of chronic headaches only, and no biofeedback benefits. Included was a sensitivity analysis of effects from a variety of biofeedback treatment schedules. Utilization of Diagnostic X Rays Skull, chest, and upper gastrointestinal tract diag- nostic x-ray procedures are the leading radio- logical expenditures for ambulatory care ser- vices. An assessment was completed ana- lyzing clinical indications (i.e., referral crite- ria) for ordering these x-ray examinations and the effects of the radiologists' reports on the diagnosis, treatment, and outcome of pa- tients. (This study was supported in part by a grant from the FDA's Bureau of Radiological Health. ~ Serum Alpha-Fetoprotein Increasing California State legislative interest in this procedure could require KPMCP to provide serum alpha-fetoprotein screening tests to 30,000 pregnant women each year, followed by a series of costly technical procedures (in- cluding ultrasonography and amniocentesis) when positive. An assessment compared the consequences of screening versus no screen- ing of this subpopulation. Sources Collen, M. F., Director, Technology Assessment, Department of Medical Methods Research, The Per- manente Medical Group, Inc. 1982. Technology As- sessment in Prepaid Group Practice (see Appendix B). Collen, M. F., Consultant in Technology Assess- ment, Department of Medical Methods Research, The Permanente Group, Inc. 1985. Personal communica- tions. The Permanente Medical Group, Inc., Depart- ment of Medical Methods Research. 1983. A Technol- ogy Assessment of Care for End-Stage Renal Disease (ESRD) for the Kaiser-Permanente Medical Care Pro- gram Northern California Region.

MecItror~ic, Inc. 3055 OIcl Highway Eight P.O. Box 1453 Minneapolis, MN 55440 (612) 574 4000 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety l _ Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benef~t _ X X _ Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded Application of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods X Laboratory testing X Clinical trials X Epidemiological and other observational methods X Cost analyses X Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $38,000,000* * This is an estimate of total 1985 research and development (R&D) expendi- tures, about 9 percent of the company's annual sales. No line item exists for tech- nology assessment, for which expenditures are considerably less than this amount. Clinical trials expenditures vary according to stage of development of major prod- ucts; e.g., Medtronic spent roughly 7 percent of its 1983 heart pacing product R&D budget on clinical trials. MEDTRONIC, INC. Introduction Medtronic, Inc., designs, manufactures, and markets heart pacemaker systems, neu- rological systems, mechanical heart valves, and instrumentation for medical diagnosis and monitoring. The company's service oper- ations include patient monitoring (e.g., am- 347 bulatory heart monitoring) and physician ed- ucation. Medtronic is the world's leading producer of implantable medical devices, both in terms of sales and number of units sold. As of 1983, one million Medtronic pace- makers and ten thousand Medtronic mechan- ical heart valves had been implanted in hu- mans. Cardiac pacing products and services accounted for 83 percent of Medtronic's

348 $422.7 million in fiscal 1984 sales. Medtronic accounted for an estimated 40 percent of the total 1982 pacemaker market in the United States, where 130,000 implantations are per- formed annually (Standard & Poor's, 1983~. Medtronic employs approximately 5,000 people around the world and does business in over 75 countries. From 25 to 30 percent of Medtronic's 1983 sales were to overseas mar- kets. International production facilities are located in Brazil, Canada, France, and The Netherlands. U.S. plants are located in Ar- izona, Colorado, Massachusetts, Michigan, Minnesota, and Puerto Rico. World head- quarters are in Minneapolis. Medtronic was incorporated in Minnesota in 1957. Purpose The purpose of Medtronic's evaluation ac- tivities is to produce products of high quality and reliability, and to build the knowledge and expertise on which future products are based. Subjects of Assessment Medtronic evaluates its medical devices, materials (e.g., polymers, metals, and ce- ramics), components (e. g., microelectronic circuits), fabrication methods, and applica- tion/implantation methods used for its prod- ucts. In 1984, Medtronic was evaluating a vari- ety of new products in various stages of devel- opment. These included a cystic fibrosis screening system, a portable blood pressure monitor, several cardioversion-defibrillation products, vascular prostheses, sensors for rate-responsive pacing, blood gas monitors, computer-enhanced imaging systems for di- agnosis and stress testing, and a microproces- sor-based artificial heart valve monitor. Also under evaluation were electrode gels, electro- chemical sensors, drug administration (im- planted pump and reservoir) devices, rate- responsive pacing systems (which alter pac- ing rate in response to changes in patient ac- tivity), external and implantable devices for treating scoliosis, spinal cord stimulation sys- tems for treatment of chronic intractable pain, and a synthetic speech source device. ASSESSING MEDICAL TECHNOLOGY Assessment of the medical procedures in which Medtronic devices play a key role is an important element of evaluation. For exam- ple, assessments of procedures for device im- plantation are used to provide instructions for the use of pacemaker leads. Medtronic also works with materials and component suppliers to improve the func- tion, reliability, and quality of the technolog- ical elements which make up devices. Stage of Diffusion In addition to evaluating the emerging and new technologies it develops, Medtronic evaluates existing technologies for product improvement and quality control purposes. Concerns Technology evaluation is concerned with safety, efficacy, cost-benefit, cost-effective- ness, and quality of life. Comparisons are made among Medtronic products, as well as those of other manufacturers, particularly for the purpose of improving durability, de- sign features, manufacturing methods, and longevity. For example, new and existing pacemaker power sources undergo compara- tive testing. Requests The primary source of the technologies de- veloped and evaluated by Medtronic is clini- cal practice. A number of major Medtronic products originated from the ideas of clini- cians, and were developed in collaboration with Medtronic. Some ideas for products have resulted from reconsideration of tech- nologies which had been evaluated earlier, without further action at the time. Medtronic has assembled medical panels to discuss the capabilities of current products and to explore clinical need and directions for new product development. Other sources for product development and improvement ef- forts include reports of clinical engineers studying Medtronic products and detailed analyses of returned devices. These sources are particularly useful for development and improvement of device components, fabrica- tion methods, and manufacturing controls.

APPENDIX A: PROFILES Selection There is no formal process for selecting technologies to be evaluated; technologies which are designed to meet clinical needs and which show promise are those which are allo- cated resources for development and further evaluation. Process The evaluation process varies according to the product, e. g., entirely new products usu- ally undergo different evaluations than do modifications of existing products. Evalua- tions generally begin with a literature review and extend through preclinical testing and clinical trials with review points where it is determined whether adequate promise exists to begin subsequent stages of the assessment. Thus, satisfactory results of preclinical test- ing must precede the support of clinical eval- uation in humans. Computer modeling is used in some circumstances. Food and Drug Administration (FDA) study requirements are followed wherever applicable. Medtronic has various sources of data for follow-up study of pacemakers and other of its prod- ucts. Medtronic conducts so-called phase IV follow-up studies as a condition of FDA ap- proval for marketing certain devices. Med- tronic maintains a registry of device implan- tation data and implant experience. (When Medtronic pacemakers are implanted, physi- cians complete implant data reports which are collected and compiled by Medtronic). Implant physicians are kept apprised of expe- rience related to the lots of devices that they have implanted and are encouraged to report to the company any further information re- garding implant experience. Medtronic also conducts telephonic monitoring of pace- makers, and expects to reach 15O,OOO pa- tients through this service by 1988. Assessors Each Medtronic business group (these are the Components and Instruments Group, Pacing Systems Group, International Group, and New Businesses Group) is responsible for the evaluation of its products along with its 349 other business operations. Evaluations are undertaken by a wide range of experts in technology, science, and medicine. Examples include biochemists, physicists, polymer chemists, electrical engineers, clinical engi- neers, cardiologists, and orthopedic sur- geons. Consisting of the executives of the business groups, The Corporate Research and Tech- nology Committee coordinates work across business groups based on corporate strategies and provides a channel for sharing evalua- tion findings and other developments. A ma- jor role of the committee is to review major proposed and new technologies which repre- sent significant departures from those being used currently. Corporate research expendi- tures are based on the committee's findings. Turnaround Complete evaluation of a major new prod- uct, including clinical studies and FDA re- view, generally requires several years. Some products require more time for development and evaluation. The time from initial re- search to marketing of the single-channel sco- liosis system (discussed under Example be- low) was 12 years, followed by several years of postmarketing study and reporting re- quired by the FDA. An improvement in an existing product, the heart valve, required 5 years from conception to marketing. Minor changes, such as modification of a lead con- ductor or a software change in a programma- ble pacemaker, take less time. Due to differ- ing regulatory requirements for evaluation, marketing outside the United States may oc- cur several years earlier than U.S. marketing for a given product. Reporting Medtronic provides appropriate reports to the FDA to obtain premarket approval for its products. Medtronic also prepares reports for clinicians who will use Medtronic devices, showing the results of evaluations, particu- larly those conducted in a clinical setting. Clinicians involved in Medtronic studies fre- quently report clinical findings to their peers through published literature and at confer-

350 ences and symposia. Company technical spe- cialists and scientists also report through these forums. In addition to Medtronic's own reporting, considerable independent evaluation of Med- tronic products and similar products manu- factured by other companies is undertaken and reported in the literature. Reprints of these independent reports are often distrib- uted with Medtronic reports. Among recent examples, the Pacemaker Center, University of Southern California School of Medicine, reported on the long-term performance of pulse generators used in cardiac pacemakers manufactured by Medtronic and other man- ufacturers (Bilitch et al., 1984~. Butrous et al. (1983) compared the effect of power fre- quency high intensity electric fields on 16 dif- ferent pacemaker models from six manufac- turers, including Medtronic. Hanson and Grant (1984) examined the 9-year experience during 1972-1982 of over 1,000 pacemakers in over 800 patients for such concerns as changing indications for pacing, patient sur- vival, and experience with different pace- maker types, including 10 Medtronic models. Herbert (1983) reported on three treatments of Scoliosis using electrical stimulation of muscle, including the Electro Spinal Orthosis (ESO) treatment developed by Medtronic and described below under Example. Impact FDA reviews of evaluations usually allow for the next phases of evaluation, or market- ing, in the United States. The choices clini- cians make are likely based on their own as- sessment of the clinical performance of the device, peer information, the literature, and/ or other sources. Reassessment The performance of currently used tech- nologies is continuously reassessed, based on experience in the field, analysis of returned ASSESSING MEDICAL TECHNOLOGY products, and in-house bench testing of pro- duction samples. Funding/Budget In fiscal year 1984, Medtronic invested ap- proximately 9 percent of sales, i.e., $37.6 million, in research and development. In 1984, Medtronic predicted that over $250 million would be devoted to research and de- velopment over the next 5 years. Example On the following pages is the table of con- tents and introduction only to a 15-page re- port of the clinical evaluation of the "Med- tronic Scoliosis System Electro Spinal Orthosis (ESO) for the Treatment of Scolio- sis" (Medtronic, May 1983), which are repro- duced here with permission. The full report is a summary of current ESO clinical study results. Sources Bilitch, M., R. G. Hauser, B. S. Goldman, S. Fur- man, and V. Parsonnet. 1984. Performance of cardiac pacemaker pulse generators. PACE 7:157-161. Butrous, G. S., J. C. Male, R. S. Webber, D. G. Barton, S. J. Meldrum, J. A. Bonnell, and A. J. Camm. 1983. The effect of power frequency high in- tensity electric fields on implanted cardiac pace- makers. PACE 6:1282-1292. Flink, R. C., Director of Corporate Standards, Medtronic. 1985. Personal communication. Hanson, J. S., and M. E. Grant. 1984. Nine-year experience during 1972-1982 with 1,060 pacemakers in 805 patients. PACE 7:51-62. Herbert, M. A. 1983. The treatment of Scoliosis us- ing electrical stimulation of muscle. Engineering in Medicine and Biology. September:43-49. Medtronic, Inc. 1983. Medtronic Scoliosis Systems Electro Spinal Orthosis (ESO) for the Treatment of Scoliosis: Clinical Study Results. Minneapolis. Medtronic, Inc. 1985. Annual Report, 1984. Min- neapolis. Standard & Poor's Corporation. 1983. Industry Surveys. Health Care: Basic Analysis 151:H13-H35.

APPENDIX A: PROFILES Med~ron~c Scohosis System™ Electro Spinal Orthos~s (ESO) For ache Reagent of Scohosis 351 CLINICAL STUDY RESULTS May 1983 NOTE: This report is only a summer\ of current ESO clinical studs results. The ESO study will continue Until sufficient data have been collected to confirm safety and efficaes~ of the ESO system, pursuant to U.S. requirements. More specific information is available if req~lircd be contacting Medtronie, Attention: Seoliosis Marketing, at the address oh the back cover. Your comments on this report `~ill he most appreciated. ~ Copyright 1983, Medtronic, Inc. All rights reserved.

352 ASSESSING MEDICAL TECHNOLOGY Table of Contents I. Introduction II. Demographic Information ............................... III. Singlc-Channel Results: Curve Change from Initial to Latest Follow-Up ............................................ IV. Singlc-Channel Results: Average Cunve Size Over Time ...... V. Dual-Channel Results .... VI. Conclusions ............ APPENI)IX—Physicians Reporting Results for Protocol Patients Illus~adom 4 6 8 11 14 . 15 16 Figure 1. MEDTRONIC~ Single-Channel ESO System 5 Figure 2. MEDTRONIC09 Dual-Channel ESO System 5 Figure 3. Electrode Placement Sites 5 Figure 4. Patient Sex Distribution 6 Figure 5. Patient Age Distribution 6 Figure 6. Cunve Size Distribution 7 Figure 7. Cunve Location Distribution 7 Figure S. Single Channel Patient Distribution by Length of Time In Program 7 Figure 9. Overall Cunve Change Distribution—Initial to Latest Follow-Up 8 Figure 10. Cunve Change Over Time—All Cunves Figure 11. Cunve Change by Cunve Location Figure 12. Cunve Chance bv Initial Cunve Size Classification Figure 13. Figure 14. Figure 15. Figure 16. Figure 17. c, , Cunve Change by Patient Sex ..... Cunve Change by Risser Sign ...... Cunve Change by Initial Electrode Position .......... Cunve Change—Untreated Secondary Cunves ...... Average Curve Size Over Time bs Original Cunve Classification .................................... Figure 18. Average Cunve Size Over Time—All Patients . Figure 19. Average Curve Size Over Timc by Degree of Initial Cure e Correction ....... Figure 20. Average Curve Size Over Time by Curve Location Figure 21. Average Curve Size Over Timc by Two Initial Cunve Size Groupings 12 Figure 22. Amperage Cure e Size Over Timc by Patient Sex 12 Figure 23. Average Curve Size Or er Time—Compliant vs. Non-Compliant Patients ........................... Average Curt e Size Over Time by Current Patient Status Dual-Channel Patient Distribution by Length of Time in Program 14 Figure 26. Cunve Change by Upper and Lower Cunves 14 Figure 24. Figure 25. 9 . 9 . 9 . 10 .. 10 12 13 13

APPENDIX A: PROFILES I. Introcluction Medtronic first became involved in the area of scoliosis in 1971 when approached by Dr. Newton McCollough, University ofMiami, who was interested in the concept of stimulating the muscles of the back to treat scoliosis. In 1972-73, Medtronic worked with Dr. McCollough in designing a stimulation unit. In 1974, a pilot study was initiated to investigate the possibility of using such surface stimulation. As the study progressed, a national study group was formed in 1977 under Dr. McCollough's directorship. This study group is the foundation of the data collected and presented in this report. Thc MEDTRONIC0 ESO (Electro Spinal Orthosis) system consists of a stimulator, clcarical cables, and electrodes. Thc stimulator contains the power source and the electronic circuitry of the system. The cables and electrodes transfer intermittent pulses to the patient. Objectives Thc primary objectives of the clinical investigation have been to demonstrate the safety, efficycv, and reliability of Medtronic scoliosis stimulation devices (single and dual channel models). Specifically, the objectives are: 1. To evaluate the Electiveness of this treatment in stabilizing single lumbar, thoracolumbar, thoracic, or double major idiopathic scoliotic curves by comparing curve measurement before treatment and at appropriate times during and following the conclusion of treatment. 2. To evaluate patient acceptance and compliance to this form of treatment. 3. To verify the Electiveness of alternative electrode placement sites in relation to the apex and length of the curve. 4. To evaluate the success of the treatment in relation to a series of interdependent variables, including bone age maturity, initial curve size, and rates of progression. 5. To evaluate the safety of this treatment and potential side effects and complications. 353 Thc following report outlines the results to date using the MEDTRONIC0 ESO system. (Note that there arc separate sections for single- and dual-chanocl results.) Protocol A protocol was established for dhc ESO study to diffcrcntiatc patients on the basis of specific variables. In a study such as this, we cannot, of course, look at every possible application, lines must be drawn somewhere. However, we chose to study patients we felt were most likely to progress—i.c., the "worst case" group. And, within our guidelines, patients were differentiated on the basis of their likelihood of progression. It should be pointed Out, Though, that these patients are not the only group that can potentially be treated. Additional clinical studies are now underway to evaluate ocher indications, such as kyphosis. Thc protocol for using the Electro Spinal Orthosis required that only patients between 20° and 40° curve measurement (using the Cobb measurement technique) be included in the study. In addition, for patients widh curves between 20° and 29°, 5° of documented progression during the previous 12-mondh period was required. The patients had to have at least one year of bone growth remaining documented by eidher Risser sign (excursion and fusion of dhe iliac crest), bone age as defined by Greulich and Pvle Adas using distal radial epiphysis, or vertebral body maturation. Curve location was defined using the guidelines of the Scoliosis Research Society. Thoracic curves included those with apex above T12. Thoracolumbar curves included those widh apex at T12 or L1, and lumbar curves included those widh apex below L1. Electrode Sites Electrodes were placed using Three general locations. Physicians selected dhe electrode site chat provided the best acute curve correction, defined as best muscle contraction. The three electrode sites were: 1. Paraspinal placement: approximately 2.5 - 4 cm from the spine and surrounding dhe curve apex. 2. Intermediate placement: approximately midway between the parasp~nal and lateral position. 3. Lateral placement: at or slightly posterior to the midaxillary line and surrounding the apical rib.

354 ASSESSING MEDICAL TECHNOLOGY Figure 1. MEDTRONICO Single-Channel ESO System Following the initial application of the ESO system, patients returned one week later for a check of electrode positions, and to obtain answers to any questions either they or their parents had concerning the device. Patients then resumed after one month for an x-ray and electrode placement check. They resumed every four months during the course of treatment for x-rays and curve measurements. If any adverse effects occurred between treatment follow-up visits, they were documented at the time of the visit and corrective measures were taken. Patient compliance was measured either by the use of patient diaries, Interrogation of the patient and parents by the physician or physical therapist or, in the case of the dual-channel device, by a 1,000-hour patient compliance meter, which operated while the device was operating. Figure 2. MEDTRONICO Dual-Channel ESO System c ~,_, Figure 3. Electrode Placement Sites

Office of Health Technology Assessment National Center for Health Services Research and Health Care Technology Assessment 5600 Fishers Lane, 3 10 Park Building Rockville, MD 20857 (301) 443 4990 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety . Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X _ X Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X Stage of Technologies Assessed X* ~ . , Mergings new X Accepted use X Possibly obsolete, outmoded Application of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $700,000 * The great majority of assessments have dealt with new technologies or new applications for existing technologies. OFFICE OF HEALTH TECHNOLOGY ASSESSMENT NATIONAL CENTER FOR HEALTH SERVICES RESEARCH AND HEALTH CARE TECHNOLOGY ASSESSMENT Introduction The Public Health Service (PHS) has been responding to requests for assessments from the Social Security Administration, and to the Health Care Financing Administration (HCFA), since the late 1960s. The Office of 355 Health Technology Assessment (OHTA), of the National Center for Health Services Re- search and Health Care Technology Assess- ment (NCHSRHCTA), under the Office of the Assistant Secretary for Health, has the di- rect responsibility for conducting technology evaluations and making recommendations in response to HCPA requests. OHTA (origi- nally as the Office of Health Research, Statis- tics, and Technology assumed these respon- sibilities following the dissolution of the National Center for Health Care Technology

356 (NCHCT) in 1981. Other assessment activi- ties of the NCHSRHCTA are discussed else- where in this report. Among the technology assessment and in- formation dissemination duties of OHTA/ NCHSR described in the Federal Register (January 19, 1983; Vol. 48, No. 13, p. 2444) are · administer a program of assessments of health care technologies which take into ac- count their safety; efficacy; cost-effective- ness; and social, ethical, and economic im- pacts, and · make recommendations on health care technology issues in the administration of the laws under the Assistant Secretary for Health's jurisdiction, including preparation of the PHS position regarding appropriateness of Medicare coverage of health care technology. In late 1984, Congress (in P.L. 98-551) re- named the National Center for Health Ser- vices Research (NCHSR) the National Center for Health Services Research and Health Care Technology Assessment, and set aside $3 million of its FY 1985 budget (and $3.5 million in FY 1986 and $4 million in FY 1987) specifically for technology assessment. This increased support is primarily intended to strengthen the agency's ability to make rec- ommendations regarding Medicare coverage issues. Purpose The objective of the OHTA evaluation is to provide HCFA with the most current infor- mation on health care technology to support coverage decisions. To assist HCFA in decid- ing what diagnostic and therapeutic tech- niques and procedures ought to be covered by Medicare, OHTA carries out evaluations of .celec~ted technologies. The final decisions on coverage are made by HCFA; the PHS has neither statutory nor regulatory authority to decide such matters. (See Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evalua- tion t1984] for a detailed description of the HCFA coverage decision process.) The basis for HCFA requests for informa- tion was originally outlined in an administra- ASSESSING MEDICAL TECHNOLOGY tive agreement between HCFA and PHS. Under the agreement HCFA sought recom- mendations regarding . . . the safety and clinical effectiveness of med- ical products or procedures identified by HCFA for which a coverage determination cannot be made by HCFA on the basis of existing policies and rules, prior coverage determinations, or prior advice from PHS (OHTA, 1983~. Subjects of Assessment Technologies to be assessed may include anv discrete and identifiable techniques or procedures used to diagnose or treat illness, prevent disease, maintain patient well-being, or facilitate the provision of health care ser- vices. Table A-9 shows the OHTA Assessment Report Series and coverage recommendations made to HCFA. Stage of Diffusion Subjects for OHTA assessment may range from practices that are obsolete or of ques- tionable effectiveness to new technologies, ei- ther those recently introduced into medical practice or those still in an investigational stage. Thus far, the majority of assessments have dealt with new technologies or new ap- plications for existing technologies. Concerns Although the duties prescribed for OHTA/ NCHSR by Congress include assessments that take into account cost-effectiveness and so- cial, ethical, and economic impacts, the pri- mary concerns to date of OHTA in making its coverage recommendations are the safety and clinical effectiveness of the technology. In addition, appropriateness (as an adjunct or alternative to conventional practice or standard accepted practice) and desirable skills, facilities, and support systems may be addressed. Cost is not an explicit concern for purposes of HCFA coverage decisions. OHTA may recommend that the technology not be covered by Medicare, that it be cov- ered with certain restrictions, or that it be covered without restriction. In making coverage determinations for

APPENDIX A: PROFILES TABLE A-9 OHTA Assessment Report Series and Coverage Recommendations 357 Volume Recommendation Volume 1, 1981 1. Alcohol Aversion Therapy 2. Hydrotherapy (Whirlpool) Baths for Treatment of Decubitus Ulcers 3. Ultraviolet Light for Treatment of Decubitus Ulcers 4. Transsexual Surgery 5. Urine Autoinjection (Autogenous Urine Immunization) 6. Apheresis in the Treatment of Rheumatoid Arthritis 7. Stereotaxic Depth Electrode Implantation 8. Cytoxic Leukocyte Test for the Diagnosis of Food Allergies 9. Sublingual Provocative and Neutralization Therapy for Food Allergies 10. Intracutaneous (Intradermal) and Subcutaneous Provocative and Neutralization Testing and Neutralization Therapy for Food Allergies 11. Intracranial Pressure Measurement 12. B-Scan of Peripheral Vessels 13. Tinnitus Masker 14. Percutaneous Transluminal Angioplasty for Treatment of Arteriosclerotic Obstructions in the Lower Extremities 15. Transcutaneous Electrical Nerve Stimulation for Treatment of Post-Operative Incision Pain 16. Shortwave Diathermy 17. Human Tumor Stem Cell Drug Sensitivity Assays for Predicting Anticancer Drug Effects 18. EDTA Chelation Therapy for Atherosclerosis 19. Ultraviolet Absorbing Lenses for Aphakic and Pseudophakic Patients 20. Bentonite Flocculation Test in Rheumatoid Arthritis 21. Desoxyribonucleic Acid-Bentonite Flocculation Test in Rheumatoid Arthritis 22. Mycoplasma Complement Fixation Test in Rheumatoid Arthritis 23. Kunkel Test in Rheumatoid Arthritis 24. Technetium-99m Pertechnetate Joint Scans in Arthritis 25. Anti-Inhibitor Coagulant Complex in Hemophilia A with Inhibitor Antibodies to Factor VIII Volume 2, 1982 Electrotherapy for Treatment of Facial Nerve Paralysis (Bell's Palsy) 2. Hyperbaric Oxygen Therapy for Treatment of Organic Brain Syndrome (Senility) 3. Hyperbaric Oxygen Therapy for Treatment of Multiple Sclerosis 4. Gastric Freezing for Peptic Ulcer Disease Bolen's Test for Cancer Bendien's Test for Cancer and Tuberculosis 7. Rehfuss Test for Gastric Acidity 8. Rheumatoid Vasculitis Therapeutic Apheresis 9. Home Blood Glucose Monitors 10. Ambulatory Blood Pressure Monitoring in Hypertensive (Semiautomatic) 11. Apheresis for Multiple Sclerosis 12. Hyperbaric Oxygen Therapy for Treatment of Arthritic Diseases 13. Plasmapheresis and Plasma Exchange for Treatment of Thrombotic Thrombocytopenic Purpura 14. Obesity and Protein-Supplemented Fasting 15. Serum Seromucoid Assay 16. Percutaneous Transluminal Coronary Angioplasty for Treatment of Stenotic Lesions of a Single Coronary Artery 17. Melodic Intonation Therapy 18. Photodensitometry 19. Bone Biopsy for Mineral Analysis or Bone Histology 6. Covered Not covered Not covered Not covered Not covered Not covered Covered Not covered Not covered Not covered Covered Covered Not covered Covered Covered Covered Not covered Not covered Covered Covered Covered Not covered Not covered Covered Covered Covered Covered Not covered Not covered Not covered Not covered Not covered Covered Not covered Not covered Not covered Not covered Covered Not covered Not covered Covered Covered Not covered Covered

358 TABLE A-9 Continued ASSESSING MEDICAL TECHNOLOGY Covered Covered Photon Absorptiometric Procedure for Bone Mineral Analysis Hyperbaric Oxygen for Treatment of Soft Tissue Radionecrosis and Osteoradionecrosis 22. Hyperbaric Oxygen for Treatment of Chronic Refractory Osteomyelitis 23. Carbon Dioxide Laser Surgery 24. Percutaneous Transluminal Angioplasty for Treatment of Stenotic Lesions of the Renal Arteries Endothelial Cell Photography 25. 26. Photoplethysmography Volume 3, 1983 1. EEG Monitoring During Open Heart Surgery 2. Apheresis for the Treatment of Goodpasture's Syndrome 3. Apheresis for the Treatment of Membranous Proliferative Glomerulonephritides 4. Electroversion Therapy for the Treatment of Alcoholism 5. Anti-Gastroesophageal Reflux Implantation 6. Closed-loop Blood Glucose Control Device 7. Plasma Perfusion of Charcoal Filters for Treatment of Pruritis of Cholestatic Liver Disease ~ , _ . Covered Covered Covered Covered Not covered Not covered Covered Covered Not covered Not covered Covered Covered 8. Topical Oxygen Therapy in the Treatment of Decubitus Ulcers and Persistent Skin Not covered Lesions 9. Fully Automated Ambulatory Blood Pressure Monitoring of Hypertension 10. Hyperbaric Oxygen for Treatment of Actinomycosis 11 . Displacement Cardiography—Photomography 12. Displacement Cardiography—Cardiokymography 13. Negative Pressure Respirators 14. Diathermy as a Physical Therapy Modality 15. Hyperbaric Oxygen Therapy for Treatment of Crush Injury and Acute Traumatic Peripheral Ischemia 16. Transplantation of the Liver Not covered Covered Not covered Not covered Covered Covered Covered Covered with guidelines 17. Computer Enhanced Perimetry Covered 18. Lactose Breath Hydrogen Test for the Diagnosis of Lactose Malabsorption Covered 19. Implantable Chemotherapy Infusion Pump for the Treatment of Liver Cancer Covered 20. External Infusion Pump for Heparin Covered 21. Lactulose Breath Hydrogen Test for Diagnosing Small Bowel Bacterial Overgrowth Not covered and Measuring Small Bowel Transit Time 22. Thermography for Breast Cancer Detection Volume 4, 1984 1. Transillumination Light Scanning for the Diagnosis of Breast Cancer 2. Implantable Pump for Chronic Heparin Therapy 3. Electrotherapy for Treatment of Facial Nerve Paralysis 4. SCOW Breath Test for Diagnosing Bile Acid Malabsorption 5. Noninvasive Method of Monitoring Cardiac Output by Doppler Ultrasound 6. Ambulatory Electroencephalographic (EEG) Monitoring 7. JACOB Breath Test for Diagnosing Fat Malabsorption 8. Transcutaneous Electrical Nerve Stimulation for Acute Pain Treatment for Ambulatory Patients 9. Apheresis Used in Preparation for Kidney Transplant 10. Carbon Dioxide Lasers in Head and Neck Surgery 11. Hyperbaric Oxygen Therapy for Acute Cerebral Edema 12. Intraoperative Ventricular Mapping 13. Apheresis in the Treatment of Chronic Relapsing Polyneuropathy 14. 15. - -r -- - - ---- --- --- - - - - ~ ---- --- - _ _ _ _ _ _ __ _ Diagnostic Endocardial Electrical Stimulation (Pacing) Neuromuscular Electrical Stimulation in the Treatment of Disuse Atrophy in the Absence of Nervous System Involvement Not covered Not covered Not covered Not covered Not covered Not covered Covered Not covered Covered Not covered Covered Not covered Covered Covered Covered Covered

APPENDIX A: PROFILES TABLE A-9 Continued 359 16. Hyperbaric Oxygen for Treatment of Chronic Peripheral Vascular Insufficiency 17. Hyperbaric Oxygen in Treatment of Severed Limbs 18. External Counterpulsation 19. Transplantation of the Pancreas 20. Streptokinase Infusion for Acute Myocardial Infarction 21. Nd:YAG Laser for Posterior Capsulotomies 22. External Open-Loop Pump for the Subcutaneous Infusion of Insulin in Diabetics 23. Laser Trabeculoplasty for Open-Angle Glaucoma 24. Local Hyperthermia for Treatment of Superficial and Subcutaneous Malignancies 25. Percutaneous Transluminal Angioplasty for Obstructive Lesions of the Aortic Arch Vessels 26. Percutaneous Transluminal Angioplasty for Obstructive Lesions of Arteriovenous Dialysis Fistulas Volume 5, 1985 1. Extracorporeal Shock Wave Lithotripsy (ESWL) Procedures for the Treatment of Kidney Stones 2. Percutaneous Ultrasound Procedures for the Treatment of Kidney Stones 3. Transurethral Ureteroscopic Lithotripsy Procedures for the Treatment of Kidney Stones 4. Debridement and Other Treatment of Mycotic Toenails 5. 24-Hour Ambulatory Esophageal pH Monitoring 6. Thermography for Indications Other than Breast Lesions 7. Allogeneic Bone Marrow Transplantation for Indications Other than Aplastic Anemia and Leukemia 8. Autologous Bone Marrow Transplantation (ABMT) 9. Stereotactic Cingulotomy as a Means of Psychosurgery 10. Reassessment of Cardiokymography 11. Patient Selection Criteria for Percutaneous Coronary Angioplasty of a Stenotic Lesion in a Single Coronary Artery 12. Bilateral Carotid Body Resection 13. Portable Hand-Held X-Ray Instrument (Lixiscope) 14. Magnetic Resonance Imaging (MRI) 15. Apheresis in the Treatment of Guillain-Barre Syndrome 16. Dual Photon Absorptiometry for Measuring Bone Mineral Density Not covered Covered Not covered Not covered Not covered Covered Not covered Covered Covered with guidelines Not covered Not covered Covered Covered Not covered Covered with guidelines Covered with guidelines a Covered with guidelines Not covered Not covered Not covered Covered with guidelines a a a a a NOTE: In this table are titles of OHTA assessment reports and the respective coverage recommendations made to HCFA. OHTA assessment reports are available in annual bound volumes (NCHSR Health Technology Assess- ment Series: Health Technology Assessment Reports') from the National Technical Information Service, and indi- vidual reports and recommendations are available from the NCHSRHCTA. See the reports for the full wording of the assessment topics and complete report narratives. The recommendations cited here do not reflect fully the discussion presented in the assessment reports. aNo instructions issued as of July 1985. SOURCE: OHTA, 1985. technologies involving drugs and/or medical devices, HCFA considers whether FDA has found the product safe and effective. HCFA generally does not approve coverage of such a technology unless FDA has already approved it. HCFA considers it to be necessary but not sufficient that a technology be safe and effec- tive in order for it to be reasonable and neces- sary. HCFA will not necessarily approve cov- erage for all technologies that FDA has approved, largely~ because the two agencies differ in their respective definitions of effec- tiveness. FDA deems a technology effective if it does what the manufacturer claims it will

360 do, whereas HCFA considers the effective- ness of the technology with respect to health outcome. If a new technology in question is a medi- cal product and has received FDA approval for commercial distribution, the thrust of the OHTA assessment is toward the use of that product in a nonidealized setting, i.e., the setting in which providers in conventional practice circumstances have demonstrated the safety and clinical effectiveness of the procedure. However, if the technology in question is a health care service, not product dependent, the thrust of the OHTA assess- ment encompasses safety and clinical effec- tiveness data as determined by clinical and scientific information published in peer re- view journals, as well as input from NIH and medical specialty societies. Requests Questions on the coverage of a particular technology under the Medicare program are forwarded to OHTA from HCFA. These re- quests may originate in an organization in the public or private sector or be initiated by an individual or group having an interest in the safety and effectiveness of health care technologies. Sources have included the re- gional offices of HCFA, Congress, commer- cial insurers and other fiscal intermediaries, clinical centers, medical societies, private phy- sicians, and medical device manufacturers. Selection Before HCFA requests OHTA to assess a health care technology, HCFA's Physicians Panel decides whether the question raised warrants an assessment. The panel considers the importance of the issue, the adequacy of the database, and the status of FDA approval before recommending that an assessment be conducted by OHTA. Process The OHTA assessment process has four stages, as follows. 1. Initiation. Prior to conducting a full as- sessment, OHTA in conjunction with HCFA ASSESSING MEDICAL TECHNOLOGY reviews the questions to be addressed by the assessment to determine the information need that initiated the original inquiry. OHTA staff work with the HCFA Bureau of Eligibility, Reimbursement and Coverage (BERC) and Physicians Panel to ensure that the questions posed are appropriate and clearly defined. Then OHTA conducts a pre- liminary analysis of the issues and reports back to BERC and the HCFA Physicians Panel if further clarification is required. 2. Collection of Information. OHTA an- nounces the impending assessment in the Federal Register, generally providing 90 days for public response. The agency also conducts a literature search with MEDLARS II com- puter retrieval service and Index Medicus. OHTA routinely contacts medical societies such as the Council on Medical Specialty So- cieties, the American Medical Association, and the American College of Physicians and manufacturers' associations for information on the technology under consideration. OHTA also seeks advice and assistance from appropriate federal agencies. These agencies may supply scientific information, clinical trial data, bibliographic material, or other pertinent information. Agencies that OHTA contacts frequently, including NIH, FDA, HRSA, ADA~HA, CDC, and VA, have de- veloped formal procedures for responding to OHTA's requests. 3. Synthesis of Information. The third stage in the assessment is the synthesis of the available information by OHTA staff in or- der to develop the PHS recommendations. The synthesis involves three steps: a. All pertinent information, including expert opinions, is summarized. b. Logical, or at least defensible, conclu- sions are formulated about the technolo- gy's safety and effectiveness. c. OHTA's policy recommendations to HCFA regarding Medicare coverage of the technology are developed. OHTA cov- erage recommendations are not included in the assessment reports, but are submit- ted separately. 4. Distrioution of Results. The final stage in the process is the dissemination of OHTA's synthesis and findings after HCFA has made

APPENDIX A: PROFILES its coverage decision. Assessment reports are made available to the public. The OHTA assessment process is continually subject to review and adoption of improved assessment techniques. Assessors OHTA assessments are conducted by OHTA staff in cooperation with outside ex- perts and other federal agencies, as described above. Coverage recommendations made by the director of OHTA are approved by the Office of the Assistant Secretary for Health before being forwarded to HCFA. The OHTA staff has seven professionals (five of whom perform assessments, including four physicians) and three support staff members. Turnaround The time between receipt of a request from HCFA to the time of transmittal of an evalu- ation and recommendation from OHTA is approximately 6 to 12 months. This normally includes time for advance notice of assess- ment, sending out requests for and receiving information, and drafting and review of the assessment report. Reporting Under the working agreement between HCFA and PHS, OHTA may publish and disseminate results of its assessments. How- ever, the OHTA report is usually not released prior to the time HCFA issues instructions re- garding coverage of the technology in ques- tion. Once the actual decision concerning Medicare coverage is made, HCFA notifies its contractors and fiscal intermediaries of its decision through formal instruction. State Medicaid agencies are also notified because they often base their determination for cover- age on the OHTA assessment. The assessments are disseminated to physicians, hospital admin- istrators, health insurers, manufacturers, and others in the health field. From 1981 through early 1985, PHS has provided over 100 assessment reports, with recommenda- tions, to HCFA. These reports are available in annual bound volumes (`NCHSR Health Technology Assessment Series: Health Tech- 361 nology Assessment Reports) from the Na- tional Technical Information Service, and are published in the American Hospital Asso- ciation Hospital Technology Series Guideline Reports, which are provided to over 1,200 hospitals. Table A-10 shows the general out- line of OHTA assessment reports. Impact HCFA has always accepted the medical and scientific aspects of OHTA recommenda- tions, although it implements coverage rec- ommendations in keeping with legal and ad- ministrative requirements (Young, 1983~. Of the 103 OHTA assessments listed in Table A-9, OHTA recommended coverage for 52 and noncoverage for 51. After receiving PHS recommendations, HCFA generally requests PHS to review the new Medicare Manual Statement, which reflects those recommen- dations, prior to the issuance of a coverage policy. Then HCFA independently makes the actual coverage decision and notifies Medicare intermediaries and the state Medi- care agencies. Reassessment HCFA or other agencies or persons may re- quest OHTA to reassess a technology in light of new information. This process is similar to the original assessment initiation process ex- cept that OHTA requests other PHS agencies to review additional information. OHTA synthesizes the findings and develops a posi- tion on the need for reassessment. The result- ing recommendations are forwarded to HCFA for consideration by its Physicians Panel. If the Physicians Panel determines that a reassessment is necessary, OHTA initi- ates the assessment described above. An example of a reassessment is that of the treatment of senile macular degeneration by argon laser photocoagulation. The Septem- ber 1980 PHS recommendation to HCFA was that this therapeutic procedure not be cov- ered. During the following year, the Na- tional Eye Institute (NEI) supported a ran- domized clinical trial of safety and clinical effectiveness of the procedure, and con- cluded that it is safe and clinically effective. In light of these findings, OHTA recom-

362 ASSESSING MEDICAL TECHNOLOGY TABLE A-10 General Outline of OHTA Technology Assessments Technology name (generic terminology, if appropriate) Description of the technology 1. What is it? 2. Who does it? 3. On whom? 4. Why is it done (objective)? Is the intervention intended to be therapeutic? Is the intervention intended to palliate or prevent further regression or deterioration? If the intervention is diagnostic, is the information obtained unique when compared with conventional procedures? Will this diagnostic information affect therapy when compared with conventional practice? ~. Are there conventional procedures used to achieve the same objective? 6. Where is it done? 7. How is it done? 8. How often is it done? 9. Is there a national demand/need for this technology? 10. Is the technology permanent, temporary, or replaceable in terms of its application and/or patient contact? Rationale A statement outlining the theoretical basis for the use of this technology for this indication. Review of published peer-reviewed medical and scientific literature to include a summary of the: 1. Issues to be addressed in the published literature 2. Study design (double blind, multicentered cooperative, comparative, serial clinical experience, etc.) 3. Size of patient population 4. Characterization of patient population 5. Length of follow-up 6. Recurrence rate, if any 7. Statistical analysis of data 8. Animal or cadaver studies, if appropriate 9. Analyses of matrix data table (reliability, significance of data to determine if the evidence supports the conclusions) 10. Other information Discussion 1. Have the issues been addressed in the literature? 2. Problems, if any, with the published clinical studies: a. Design of clinical studies (controlled, serial experience, multicentered cooperative, etc.) b. Size of patient population (large, small, representative, homogeneous, heterogeneous, etc.) c. Follow-up: consistency, duration, epidemiologic disciplines used d. Recurrence rate, if any e. Statistical analysis of data, if any f. Animal studies, cadaver studies, etc., if appropriate 3. Safety considerations: a. Known risks—probable/predictable risks b. Criteria, if any, for use (provider) performance (experienced hands. . . ) c. Secondary, harmful effects of the intervention, if any . Citations of review articles that draw comparisons between the new technology and conventional practices 5. Regulatory status, if a product is under review 6. Other nonmedical, nonscientific controversies, if any Summary Statement should contain: 1. Description of differences, if any 2. A statement regarding the supportability of the rationale 3. A description of evidence 4. Level of acceptance of the technology by both the research and clinical practice communities 5. The appropriateness of the new technology as an adjunct or alternative to conventional practice or standard accepted practice 6. Degree of difficulty/sophistication as it affects the needs for special resources and skills 7. Specific characteristics of institution, medical team, etc., involved in use of technology References—All published studies/reports reviewed in this submittal, attach cited literature SOURCE: OHTA, 1983.

APPENDIX A: PROFILES mended in June 1982 that the procedure be covered under Medicare. Other technologies that have been reassessed include liver trans- plants, hyperthermia for the treatment of cancer, and implantable chemotherapy infu- sion pumps. Funding/Budget OHTA budgeted approximately $0.7 mil- lion in 1985 for technology assessments for HCFA and related activities. Example On the following pages is the full text of the 1984 OHTA assessment of percutaneous transluminal angioplasty for obstructive le- sions of arteriovenous dialysis fistulas. Sources Brandt, E. N. 1984. Technology assessment, a pri- vate-public partnership. Public Health Reports 99:329-330. Carter, E., Director, Office of Health Technology Assessment. 1985. Personal communications. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evalua- tion. 1984. Technology Assessment and Coverage De- cisionmaking in the Department of Health and Hu- man Services. Prepared by Macro Systems, Inc. Erlichman, M., Evaluation Staff, Office of Health Technology Assessment. 1985. Personal communica- tions. 363 Federal Register. January 19, 1983; Vol. 48, No. 13, p. 2444. Margulies, H., Director (former), Office of Health Technology Assessment. 1983. Personal communica- tions. National Center for Health Services Research. 1984. Health Technology Assessment Series: Health Technology Assessment Reports, 1981, nos. 1-25. DHHS Publication No. (PHS) 84-3370. Springfield, Va.: National Technical Information Service. National Center for Health Services Research. 1984. Health Technology Assessment Series: Health Technology Assessment Reports, 1982, nos. 1-26. DHHS Publication No. (PHS) 84-3371. Springfield, Va.: National Technical Information Service. National Center for Health Services Research. 1984. Health Technology Assessment Series: Health Technology Assessment Reports, 1983, nos. 1-22. DHHS Publication No. (PHS) 84-3372. Springfield, Va.: National Technical Information Service. Office of Health Technology Assessment, National Center for Health Services Research and Health Care Technology Assessment, Department of Health and Human Services. 1984. Public Health Service Assess- ment of Percutaneous Transluminal Angioplasty for Obstructive Lesions of Arteriovenous Dialysis Fistu- las. Rockville, Md. OHTA. 1982. Memorandum regarding coverage of treatment of senile macular degeneration by argon la- ser photocoagulation, June 9. Rockville, Md. OHTA. Listing of requests returned from PHS, Oc- tober 1979 through April 1983. Rockville, Md. OHTA. 1983. Public Health Service Procedures for Evaluating Health Care Technologies for Purposes of Medicare Coverage. Rockville, Md. Young, D., Deputy Director, Bureau of Eligibility, Reimbursement and Coverage, Health Care Financ- ing Administration. 1983. Personal communication.

364 ASSESSING MEDICAL TECHNOLOGY PUBLIC HEALTH SERVICE ASSESSMENT OF PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY FOR OBSTRUCTIVE LESIONS OF ARTERIOVENOUS DIALYSIS FISTULAS 1984 INTRODUCTION Percutaneous transluminal angioplasty (PTA) is an angiographic treatment for vascular occlusive disease. The technique consists of vascular dilation and recanalization that is associated with the restoration of blood flow through segmentally diseased arteries (1~. PTA involves passage of a balloon-tipped catheter to the site of arterial narrowing and inflation of the balloon to reduce the obstruction (2~. The first clinical dilation of blood vessels was described by lD otter and Judkins in 1964 (3~. They used a "stiff," coaxial catheter system to develop the technique of PTA. Initially, the catheter system was applied to short segment obstructions of the femoro-popliteal region and later to iliac arteries (4~. In the early 1970's Gruntzigs development of a "flexible," double lumen, balloon-dilating catheter permitted extension of the technique from the iliofemoral vessels to previously inaccessible sites such as coronary and renal arteries (5,6~. In recent years, PTA has been used to treat stenoses of aortic arch vessels and stenotic segments of failing arteriovenous (AV) fistulas. The creation of an AV fistula in the forearm is used to facilitate access to the vessels in patients with end-stage renal failure treated by hem odialysis. Presently, the surgically created subcutaneous AV fistula is the primary mode of vascular access for chronic he modialysis. Complications associated with vascular access include stenosis, thrombosis, infection, and cardiac failure associated with high fistula flow. Access malfunction may be manifested by graft and fistula thrombosis, elevated venous pressure resulting in excessive ultrafiltration, and decreased Hood flow resulting in inefficient dialysis. The most common etiology of vascular access thrombosis is the occurrence of stenosis at sites of arterial or venous anastomosis, or the development of fibrosis at sites of repeated needle punctures (7~. The conventional surgical management of patients with obstructive lesions of failing AV dialysis fistulas has been revision or replacement of the fistula. Revision includes excision or bypass of the stenotic area and reanastomosis (8~. As complications occur, increasingly proximal revisions are performed using any suitable vessels. When the fistula is not amenable to revision, placement of a new fistula is required. Often the patient will receive an AV forearm fistula in the other arm (8~. When an autogenous fistula is no longer feasible, extended procedures with prosthetic graf ts are used. Forearm brachioantecubital loop grafts, radioantecubital straight grafts, as well as upper arm brachiobasilic loops have been employed routinely (9~. The demand f or AV access fist ulas in chronic renal failure is clearly defined by a yearly incidence of about 24,000 patients treated by chronic dialysis with a prevalence of about 72,000 patients (personal communication, HCFA). Studies of the surgical m en gem ent of fist ula complications have indicated that fistulas require revision or replacement at an average of 0.6 times per year per patient. (9~. PTA has been offered as an alternative method for restoration of flow in the arteriovenous dialysis fistulas obviating the need for conventional surgery. The purpose of this report is to assess the safety, clinical effectiveness and use of PTA in the treatment of obstructive lesions of AV dialysis fistulas.

APPENDIX A: PROFILES 365 BACKGROUN1) Chronic he modialysis became an accepted method of treatment for end-stage renal disease with the development of the Quinton-Scribner external shunt in 1960 (8~. With this technique, Teflon Silastic cannulas are inserted into the radial artery and into an adjacent forearm vein. The two ends of the cannulas that exit from the skin are then connected by a U-shaped external shunt that can be disconnected for dialysis (10~. Despite improvements in the use of the external shunt, serious complications such as frequent clotting, local and systemic infection, and erosion of the skin overlying the shunt, precluded long-term patency (11~. Mennes and coworkers (8) reviewed numerous reports where the duration of function of such shunts was from 3 to 12 months. They found that infection, clotting, or bleeding, necessitated removal and replacement of the cannula in the majority of cases. However, as a result of the external shunt more and more patients were maintained on chronic dialysis for longer periods. This necessitated repeated shunt revisions and reinsertions and made the problem of chronic access to the circulation an even more important consideration in their care. In 1966, the internal fist ula and the use of repeated venipuncture, for dialysis appeared as an alternative. Brescia and coworkers surgically created a subcutaneous AV fistula by anastomosis of the radial artery to an adjacent branch of the cephalic vein in the forearm (12~. The internal fistula provides a sufficient blood flow for dialysis through the arterialized vein. Hemodialysis is accomplished by two separate punctures of the enlarged arterialized vein with a No. 15 or 16 gauge needle. The arterial needle is placed distally toward the wrist and is used for withdrawal of blood from the patient, while the venous needle, placed proximally toward the elbow, returns the blood from the dialyzer to the patient. Satisfactory hemo&alysis requires three 6-hour sessions per week at a minimal flow rate of 200-300 ml per minute and an ideal fistula flow of 400- 500 ml per minute (13~. The &star forearm is the most practical site for fistula creation. Though fistulas mature in about 10 days, it takes three to six weeks for the vein to become "arterialized (i.e., large and thick enough to permit repeated dialysis). During mat ~ration, the overlying skin heals, a thrill develops in the veins continuous with the shunt, and these veins enlarge and become readily palpable (13~. In most patients the fistula can be constructed without difficulty. Arteries of the upper extremities are preferred since they tend to be less atherosclerotic The usual surgery is a side-to-side fistula between the radial artery and the cephalic vein near the wrist. The radial artery is the artery of choice' since it is larder in most patients and can be easily anastomosed to the adjacent . . . . . . . ... . . . . . cephalic vein. The cephalic vein is also of adequate size in most patients and has an anatomic pattern in the forearm most suitable for arterialization. If the radial artery is not available because of previous cannulations, the ulnar artery can be used. Also, the basilic vein can be used if the cephalic vein is not available and anastomosed to the ulnar artery or mobilized and anastomosed to the radial artery (14~. Though a radial-cephalic side-to-side anastomosis was originally described by Brescia and coworkers (12) other authors prefer the end vein-to-side artery anastomosis while some recommend the use of an en~to-end anastomosis (14~. Glanz and associates reported that because of blood flow characteristics, these techniques have not proved as durable as the side-to-side anastomosis (15~. Additionally, when an internal AV fistula is not feasible, a graft fistula may be inserted between an appropriate artery and vein. Various materials such as bovine carotid artery heterograft and Gor~tex expanded polytetrafluoroethylene have been used. Despite the type of anastomosis used in the formation of the subcutaneous AV fistula, complications associated with vascular access still represent one of the most frequent and significant problems encountered in a chronic hemodialysis center. Thrombosis, stenosis, venous aneurysms, infections, and cardiac failure associated with high fistula flow all contribute to the morbidity and mortality of the hem odialysis patient. Initial failure rates for most AV fistulas range from about 8 to 16 percent; however, once the fistula is established and successfully used for dialysis, the incidence

APPENDIX A: PROFILES 367 heparinzation during the procedure and low dose aspirin as a platelet inhibitor one or two days before and 3-6 months after dilatation. Some routinely add heparin for several days after dilatation and others institute warfarin anticoagulation for several months (1~. Some clinicians who perform PTA on dialysis patients do not favor the use of anticoagulants after PTA due to coagulation abnormalities that exist in some uremic patients (8~. To date, no controlled trials of the efficacy of the various post-PTA anticoagulation regimens have been reported. PTA has become a widely used technique for dilatinglesions of the ileofemoral, popliteal2 renal and coronary arteries. The Office of Health Technology Assessment has previously assessed the use of PTA in the treatment of stenotic lesions of these vessels and found the technique safe and clinically effective (4,5,6,). Until recently there has been a hesitancy to dilate obstructive lesions in veins and grafts. However, recent studies have reported the outcome of PTA treatment for stenotic lesions of AV dialysis fistulas. Since the use of PTA in AV fistulas has been used for a limited period of time in the United States only a few American studies have been reported in the recent literature. This report examines these and other studies in the published literature as well as other available evidence that pertains to the safety and clinical effectiveness of this technique. RATIONALE Proponents of PTA believe that this technique off ers a safe and effective alternative to the surgical revision or replacement of AV fistulas with stenotic or occlusive lesions. Additionally, they propose that intervention with PTA at the stenotic stage of access malfunction could prevent access occlusion and/or thrombosis. They cite several advantages of this approach including its use in ambulatory patients, the prolongation of fistula survival and its effectiveness with multiple stenoses. Proponents of PTA argue that it is a less invasive procedure that can be repeated in the event of restenosis and it neither precludes nor prejudices the outcome of subsequent surgery. Moreover, the cost of conventional surgery and hospitalization are certainly more than would be anticipated with PTA (26~. REVIEW OF AVALAB LE INFOK RATION In 1981, Lawrence and associates reported treating six hem odialysis patients with stenotic segments of failing AV fistulas by balloon catheter dilatation (17~. These patients were considered can&dates for PTA because they developed hemodynamic problems while on dialysis. Three of the six patients had successful dilatation of the AV fistulas. They included one patient with a stenosis of the midportion of a Brescia-Cimino forearm fistula, one patient with a tight stenosis 4 cm from the anastomotic site of a Brescia-Cimino AV fistula and one patient with a stenosis lust distal to the venous anastomosis of a straight forearm bovine graft. ~ .. . . ~ . . ~ .. .. Two of these fistulas were still uncuon~ng at ~ and tu montns tonowup and the third fistula functioned up to the patient's death (two months). Dilatation was unsuccessful in two patients because the stenosis located adjacent to the AV anastomosis could not be approached with the balloon. The third failure was due to the inability to pass a catheter through a very tortuous vein leading from the anastomotic site. The authors reported no complications secondary to the technique and found that the dilatation attempt did not preclude surgical revision when it failed (17~. In a related report, Spinowitz and associates attemped PTA in 12 hem odialysis patients with vascular access stenoses (7~. Though successful dilatation was achieved in six patients, vascular access patency lasted from only 3 weeks to 11 months postangioplasty; at which time surgical correction was performed in the surviving patients. The authors stated that there were no episodes of distal embolization,

368 ASSESSING MEDICAL TECHNOLOGY significant hematoma formation, or rupture of the dilated vascular access. Spinowitz and associates concluded that stenoses of short segments in the venous limb of polytetrafluoroethylene grafts, as well as Brescia-Cimino fistulas are amenable to PTA with a high degree of success and no morbidity. Recently, Glanz and colleagues reported on their 4-year experience of 56 balloon dilatations in 51 patients with failing dialysis access fistulas (27~. Internal fist ulas and grafts were evaluated and then dilated in patients presenting increased venous pressure during dialysis, arm edema, venous or graft aneurysms and pseudoaneurysms, and arterial sucking during dialysis. Forty-five lesions in graft fistulas were dilated. Of these, 38 stenoses were located at or near the venous anastomosis, three at the arterial anastomoses and four in a far proximal vein. Eleven lesions were dilated in internal AV fistulas. Of these, six venous stenoses were located within 8cm of the anastomosis and five were in a far proximal vein. The majority of procedures were performed on an outpatient basis. Glanz and colleagues found that 39 of 56 dilatations (70 percent) were initially successful, as shown by morphologic improvement of the lesion and reduction in pressure gradient (27~. Of the initial successes, 28/35 (80 percent) were patent at 3 months, 19/27 (70 percent) at 6 months, 12/22 (55 percent) at 1 year, 7/14 (50 percent) at 2 years, and 3/9 (33 percent) at 3 years. The authors reported three complications (5 percent); one internal fistula thrombosis, and one graft thrombosis within 24 hours of the procedure and one pseudoaneurysm at the dilatation site 1 year postprocedure. Because the authors did not have any successful dilatations of lesions longer than 4 cm they recommended that patients with these lesions receive surgical revision (27~. Although the long-term patency rates of fistula dilatations using PTA were not high, Glanz and colleagues believe that the nonsurgical prolongation of the life of a fistula by one or more years is still of benefit to dialysis patients who have already undergone and are still likely to undergo numerous surgical procedures during their lifetimes. Especially since repeat dilatation can be performed on recurrent lesions and patients with failed angioplasty can still undergo the surgical revision that would have been done prior to PTA (27). Satisfactory results with PTA for stenotic segments of failing AV fistulas was also reported by Hunter and coworkers (28~. A total of 31 patients with 45 episodes of failing AV dialysis fistulas were evaluated and treated by PTA and occasionally streptokinase . . . . .. .. . .. · · .. — infusion. ~lstula tallure was usually due to venous anti/or anastomotlc stenosis, often in conjunction with thrombosis. There were 28 occlusions and 17 stenoses treated. Success, defined as having remained patent for at least 6 months of continuous use, being currently patent (less than 6 months) at the time of the review, or remaining patent until the patients death or successful transplantation, was achieved in 10 of the 28 occluded episodes and in 14 of the 17 stenotic episodes (28~. The authors found occlusions associated with AV fistulas extremely resistant to dilation and the treatment of occlusions with associated thrombus even more difficult to treat. About forty-three percent (6/14) of the occlusions without thrombus were successf ully dilated while only twenty-nine percent (4/14) of the occlusions with thrombus were successfully dilated. Streptokinase and/or heparin played a critical role in three of the four "occlusions with thrombus" that were successfully dilated. The authors found stenoses associated with AV fistulas also resistant to dilation. These abnormalities were much more amenable to PTA treatment. The average patency for the 14 successfully dilated stenoses was almost 10 months. Only three stenoses could not be dilated by PTA and two of these involved multiple stenoses. Hunter and coworkers determined that most complications and failures occurred either in patients with recently created fistulas or in those with multiple or long segment stenosis associated with thrombosis. They recommend PTA as the treatment of choice in patients with a single nonobstructing stenotic AV fistula (28~.

APPENDIX A: PROFILES 369 DISCUSSION Recently, PTA has been used to dilate stenotic lesions of failing dialysis access fistulas and shunts. While recent experience suggests that there may be a wider spectrum of applications for PTA than dilating lesions of the ileofemoral, popliteal, renal and coronary arteries, there exists a paucity of published literature describing the use and safety of PTA in AV fistulas in a significant number of patients. AV fistulas are the favored vascular access for chronic he modialysis and when an internal fistula is no longer feasible a graft may be inserted. Stenotic lesions are a common problem, however, in patients with internal and graft fistulas and many of these patients have had numerous fistulas inserted and multiple revisions in an attempt to maintain adequate access for dialysis. Presently, several authors have reported the successful use of PTA to maintain adequate access for dialysis. All stress the advantages of PTA to surgery and the importance of proper selection of patients. Their experience so far, with small numbers of Datients. suggests a promising technique with a low complication rate when a careful ~ ~ ~ - r - - - ~ -A selection of patients is made and the angioplasty is performed by an experienced individual. Although recent developments, such as high-pressure balloons and long inflation time procedural refinements, of PTA have permitted clinicians to apply this technology to the problem of access stenosis, many stenoses and occlusions associated with AV fistulas have proved resistant to dilation (27-28~. Dense perivenous and en dovenous fibrosis make venous anastomotic lesions quite resistant to dilatation. Far proximal venous stenoses with endovenous fibrosis only, are easier and more successfully dilated. Glanz and coworkers suggest that the turbulence and shear stresses of arterial blood flowing into a low-resistance vein may act as the initiating event in the deposition of platelets and fibrin, resulting in mural thrombus and eventual fibrosis (15~. They reported needing as many as 8-10 balloon inflations for up to 30 seconds before a successful result was effected (27~. In order to generate the higher pressures needed to dilate fibrotic lesions, Glanz and coworkers used polyethylene, rather than polyvinyl chloride balloons. In some cases, they have also had to increase balloon inflation tinge from 30 seconds to 5 minutes in order to dilate several resistant venous stenoses (27~. Hunter and associates found that even strenuous balloon dilation can be unsuccessful with fibrotic stenotic lesions. Seven of their 10 successful dilations of occlusions and four of their five successful dilations of anastomotic stenoses required the followup use of semirigid dilators (coaxial dilation) after unsuccessful attempts with balloon dilation. Presently, rates of late patency of the dilated internal and graft fistulas are not high, and substantially more experience with PTA in AV dialysis fistulas is needed in controlled studies to better define the safety and clinical effectiveness of the procedure. The treatment of patients with obstructive AV fist ulas with PTA is a relatively new procedure that lacks adequate experience. Advice concerning the safety and efficacy of PTA for stenotic lesions of AV dialysis fistulas has been sought from groups and organizations, both within and outside of the Federal Government. However, due to the newness of this application of PTA, and the lack of adequate data and experience in its use, those organizations contacted have been unable to establish positions at this time. The Food and Drug Administration (FDA) states that percutaneous transluminal balloon dilatation catheter type devices were marketed in the U.S. before May 28, 1976, but have not been classified. Several devices of this type are currently being marketed under the terms of section 510(k) of the Medical Device Amendments of May 28, 1976, to the Food, Drug, and Cosmetic Act. According to the FI:)A, the indicated use of this type of device is to percutaneously dilate certain stenotic peripheral arteries, including the iliac, femoral, popliteal, tibial, and renal arteries. The FDA has not received any 510(k) premarket notification submissions for use of this type of device in dilating AV fistUas.

370 ASSESSING MEDICAL TECHNOLOGY SUMMARY PTA is the percutaneous, fluoroscopically guided use of balloon-tipped catheters to remove or relieve stenotic or occlusive lesions of the vascular system. Since its introduction in 1964, PTA has been widely used to treat atherosclerotic occlusive disease of the coronary, renal, iliac, and femoral arteries. However, dilation of failing AV access fist~as has been only rarely performed due to the newness of this application of PTA. Maintenance of a patent vascular access is one of the most vexing and frequent problems facing the physician who cares for patients on maintenance hemodialysis. While several authors have reported the successful use of PTA in these vessels, their experience. so far. with series of small numbers of patients, suggests a promising application of PTA with a low complication rate when careful selection of patients is made and the angioplasty is performed by an experienced individual. The treatment of patients with obstructive lesions of AV dialysis access fistulas with PTA is a relatively new procedure that lacks adequate experience. Substantially more experience with PTA in failing AV dialysis fistulas and shunts is needed in controlled studies to better define the safety and clinical effectiveness of the procedure. Prepared by: Martin Erlichman, M.S. .;b

APPENDIX A: PROFILES 371 References 1. Moore, T.S., et al. Percutaneous transluminal angioplasty in subclavian steal syndrome Recurrent stenosis and retreatment in two patients. Neurosurgery. 11 (4): 512-17(1982). 2. American College of Physicians: Health and Public Policy Committee. Percutaneous transluminal angioplasty. Annals of Internal Medicine. 99 (6): 864- 68 (1983). 3. Gruntzig, A. Recanalization of Arterial Stenosis with a Dilatation Catheter. D. Dobbelstein (ed). CEPID, Munich, 1980. 4. National Center for Health Care Technology. Percutaneous transluminal angioplasty in treatment of the lower extremities. Assessment Report Series. 1 (14):1-12 (1981). 5. National Center for Health Care Technology. Percutaneous transluminal angioplasty for treatment of stenotic lesions of a single coronary artery. Assessment Report Series. _ (24): 1-21 (1981). 6. National Center f or Health Care Technology. Percutaneous transluminal angioplasty in treatment of stenotic lesions of the renal arteries. Assessment Report Series. _ (24): 1- 13 (1984). 7. Spinowitz, BS., Carsen, G., Meisell, R. et al. Percutaneous transluminal dilatation for vascular access. Nephron. 35:201-204(1983. 8. Mennes, PA., Gilula, LA., Anderson, CB., et al. Complications associated with arteriovenous fistulas in patients undergoing chronic hemodialysis. Arch Intern Med. 138:117-21(3uly 1978). 9. 11. Giacchimo, JL, Geis, P., Buckingham, JM., et al. Vascular access: Long-term results, new techniques. Arch Surg. 114:403-408~1979~. 10. Lewis, SM. (1983) Acute and chronic renal failure in: Lewis, SM., Collier, IC., (eds) hledical Surgical Nursing. McGraw-Hill, New York, p.ll28-30. Bailey, GL., Morgan, AP. (1972) Circulatory access for he modialysis in Bailey, GL., (ed) Hemo&alysis. Academic Press., New York and London, p. 211-31. Brescia, MJ., et al. Chronic hem odialysis using venipuncture and surgically created arteriovenous fistula New England J Med. 275:1089-92~1966~. 13. Gilula, LA., Staple, TOO., Anderson, ca., et al. Venous angiography of he modialysis fistulas. Radiolo~ 115:555-62(June 1975~. 14. Ilaimov, M. Vascular access for hemodialysis. Surgery Gynec. Obstet. 141:619- 629~1975~. 15. Glanz, S., Bashist, B., Gordon, DH., et al. Angiography of upper extremity access fistulas for dialysis. Ra&ology. 143:45-52(April 1982~.

372 ASSESSING MEDICAL TECHNOLOGY 16. Kinnaert, P., Vereerstraeten, P., Toussaint, C., et al. Nine years experience with internal arteriovenous fistulas for haemodialysis a study of some factors influencing the results. Br. J. Surg. 64:242-46~1977~. 17. Lawrence, PF., Miller, FJ., Minneau, DC. Balloon catheter dilatation in patients with failing arteriovenous fistulas. Surgery. 89:439-442~1981~. 18. Hunter, DW., So, SKS., Cataneda-Zuniga, WR., et al. Failing or thrombosed Brescia-Cimino arteriovenous dialysis fistulas. Radiology. 149:105-109~1983~. 19. Anderson, CB., Gilula, LA., Harter, H., et al. Venous angiography and the surgical management of subcutaneous hemodialysis fixates. Ann Surg. 187~2~:194- 204(1 978~. 20. Gothlin, J., Lindstedt, E. Angiographic features of Cimino-Brescia fistulas. AJR. 12S(:3~:582-90(1 975~. 21. American Medical Association. Percutaneous transluminal angioplasty. Report H of the Council on Scientific Affairs. 269-71 (1982~. 22. Abele, J.E. Balloon catheters and transluminal dilatation: Technical considerations. AJR. 135:901-06 (1980). Sos, T.A., Sniderman, K.W. Percutaneous translunainal angioplasty. Seminars in Roentgenology. XVI ~ 1~:26-41 (1 98 1~. 24. Athanasoulis, CA. Percutaneous transluminal angioplasty: AJR. 135:893-900~1980~. General principles. 25. Block, PC. et al. hlorphology after transluminal angioplasty in human beings. N ENGL J Med. 305382-85~1981~. lDamuth, HD. et al. Angioplasty of subclavian artery stenosis proximal to the vertebral origin. AJNR. 41239-42~1983~. 27. Glanz, S., Gordon, D., Butt, KMH., et al. Dialysis access fistulas: Treatment of stenoses by transluminal angioplasty. Radiology. 152:637-42~1984~. 28. Hunter, DW., Castaneda-Zuniga, WR., Coleman, CC., et al. Failing arteriovenous &alysis fist ulas: Evaluation and treatment. Radiology. 152:631-35~1984~.

National Heart, Lung, and BloocI Institute Office of Program Planning ant! Evaluation BIcig. 3 ~ Room 5A 03 National Institutes of Health Bethesda, MD 20205 (301) 496 6331 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ . Effectiveness Cost-Benefit . x 1 X X ~ X Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X X X Stage of Technologies Assessed X Emerging/new X Accepted use X Possibly obsolete, outmoded A p plication of Technologies X Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods X Laboratory testing X Clinical trials X Epidemiological and other observational methods Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $26,000,000* * This estimate covers NHLBI clinical trials expenditures and expenditures for consensus development and related assessment activities. The total fiscal year (FY) 1984 NHLBI budget was over $700 million. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE NATIONAL INSTITUTES OF HEALTH Introduction The National Institutes of Health (NIH) is the principal biomedical research agency of the federal government. NIH accounts for 69 percent of all federal expenditures for health R&D and 36 percent of total national support for health R&D. NIH is composed of 12 bu- reaus and institutes (hereafter all referred to 373 as institutes), and six research and support di- visions. The National Heart, Lung, and Blood Institute (NHLBI) is the second largest in terms of funding, after the National Can- cer Institute (NCI). NHLBI was established in 1948 under au- thority of the National Heart Act as the Na- tional Heart Institute. With a growing awareness of national health problems, it was redesignated as the National Heart and Lung Institute in 1969. The activities of the institute were expanded in 1972 by the Na-

374 tional Heart, Blood Vessel, Lung, and Blood Act (P.L. 92-423) to advance the national ef- fort against diseases of the heart, blood ves- sels, lungs, and blood. With the passage of the Health Research and Health Services Amendment in 1976 (P.L. 94-278), and its redesignation as the National Heart, Lung, and Blood Institute, the authority was fur- ther enlarged to include research on the use of blood and blood products and on the man- agement of blood resources. The mission of the National Heart, Lung, and Blood Institute is to advance the nation's capabilities to prevent, diagnose, and treat heart, lung, and blood diseases. NHLBI plans, fosters, and supports an integrated and coordinated program of research, investiga- tions, clinical trials, and demonstrations re- lating to the causes, prevention, methods of diagnosis, and treatment of heart, lung, blood vessel, and blood diseases, including the uses and management of blood and blood products. Other federal agencies support cardiovas- cular, lung, and blood research as well. The Interagency Technical Committee (IATC), chaired by the director of NHLBI, coordi- nates federal health programs and activities in these areas. The 1972 act mandated that the NHLBI director, with the advice of the National Heart, Lung, and Blood Advisory Council, develop a national plan for attacking heart, blood vessel, lung, and blood diseases. The 1972 act also requires the director and Advi- sory Council of NHLBI to submit an annual report to the President, for transmittal to Congress, on the accomplishments of the na- tional program during the preceding year and on plans for the next 5 years. NHLBI as- sessment activities described in this profile are determined largely through the institute's ongoing program cycle of planning, imple- mentation, and evaluation. The major components of NHLBI are the Office of the Director, Division of Heart and Vascular Diseases, Division of Lung Dis- eases, Division of Blood Diseases and Re- sources, Division of Epidemiology and Clini- cal Applications, Division of Extramural Affairs, Division of Intramural Research, Of- fice of Program Planning and Evaluation, ASSESSING MEDICAL TECHNOLOGY Office of Administrative Management, Of- fice of Prevention and Control, and Office of Special Concerns. The Office of Program Planning and Evaluation (OPPE) coordi- nates technology assessment and technology transfer activities, and its director represents NHLBI on the NIH Coordinating Committee on Assessment and Transfer of Technology. Major program areas of NHLBI are as fol- lows. Heart and Blood Vessel Diseases arteriosclerosis* hypertension cerebrovascular disease coronary heart disease peripheral vascular diseases arrhythmias heart failure and shock congenital and rheumatic heart diseases v cardiomyopathies and infections of the heart circulatory assistance Lung Diseases structure and function of the lung chronic obstructive pulmonary diseases pediatric pulmonary diseases occupational and immunologic lung diseases respiratory failure pulmonary vascular diseases Blood Diseases and Resources bleeding and clotting disorders red blood cell disorders sickle cell disease blood resources NHLBI supports extramural research and conducts intramural research in the three categorical disease areas. The Division of Ep- idemiology and Clinical Applications plans and directs a program of epidemiological studies, clinical trials, basic and applied be- havioral research, demonstration and educa- tion research, and projects for disease pre- vention and health promotion in all three areas. * Although NHI,BI does not have direct program- matic responsibility for diabetes mellitus, it supports investigations on the metabolic effects and cardiovas- cular consequences of diabetes.

APPENDIX A: PROFILES Like other institutes, NHLBI has several advisory bodies, the foremost of which is the National Heart, Lung, and Blood Advisory Council. The council has 5 ex officio mem- bers, including the directors of NHLBI and NIH, and 18 appointed members from out- side the federal government, including scien- tists and lay community members with a demonstrated interest in relevant health areas. Among its major activities, the council makes recommendations regarding areas and relative emphasis of institute research sup- port, reviews grant applications, and submits an annual report to the President and Con- gress on the progress of the national program. The Board of Scientific Counselors advises NHLBI regarding the intramural research program. The NHLBI Clinical Trials Review Committee, Research Review Committees A and B. and Research Manpower Review Committee advise the institute by providing initial scientific merit review for studies seek- ing grant or contract support. Other program advisory committees composed of nonfederal experts review and evaluate ongoing extra- mural and intramural programs, identify fu- ture research needs and opportunities, and conduct other advisory tasks. Purpose This profile deals primarily with NHLBI clinical trials and other assessment activities such as consensus development conferences and workshops. The purpose of NHLBI tech- nology assessment activity is to serve the over- riding strategy of the institute's national pro- gram. This strategy is represented by the biomedical research and clinical applications spectrum illustrated below (Figure Am. A1- though the institute recognizes that the de- velopment and use of many medical technol- ogies have not evolved through this sequence, NHLBI efforts to guide technological evolu- tion through this spectrum are intended to maximize the beneficial effects of research findings on clinical practice and on the health-related behavior of the population. Evaluation is integral throughout this model spectrum because some aspect of evaluation is built into it in all stages. Formalized evalu- ation and validation in the form of clinical 375 1 ~ | Generation Communication Utilization and Diffusion Basic and Applied Research Research and Development L Knowledge Knowledge Validation Acquisition _ ~ ~: ~ Evaluation ~ === Development ~ , ~ nto~ Demonstration \ and Education ~ Health Programs / Practice . _ ~~ 1 ~ Knowledge ~ / j FIGURE A-1 NHLBI conception of the biomedical research spectrum. SOURCE: Moskowitz et al. (1981). trials or other validation research often oc- cur before a technology is disseminated for general use. Existing technology is contin- ually evaluated and reevaluated by practi- tioners, by patients and, in some cases, by regulatory and research agencies. Consensus development conferences, task force reports, workshops, review articles, and related re- ports evaluate the available scientific evi- dence on medical technologies, and identify problems needing further research. Subjects of Assessment The principal types of technology assessed by NHLBI are drugs, medical devices, medi- cal and surgical procedures, and support sys- tems used in prevention, diagnosis, screen- ing, and treatment. NHLBI also devotes considerable attention to the roles of smok- ing, diet, and other aspects of life-style and the environment in heart and vascular dis- eases, lung diseases, and blood diseases. One of the major NHLBI efforts addressing sup- port systems is that of the Division of Blood Diseases and Resources, which plans and di- rects programs to improve national systems of blood procurement, management, and distribution. The institute does some work in evaluating the organization of health care, e.g., assessing alternative hypertension man- agement programs, various educational pro- grams, and delivery of care by state health departments. Furthermore, it administers and evaluates the National Heart, Blood Ves- sel, Lung, and Blood Program. Topics of ongoing and completed NHLBI clinical trials are shown in Table A-7, with

376 ASSESSING MEDICAL TECHNOLOGY TABLE A-7 NHLBI Clinical Trials Since 1965 Trial Initiation/ Duration (years)a Actual/Projected Total Cost (in millions of $) Heart and Vascular Diseases Program Coronary Drug Project Coronary Drug Project Mortality Surveillance Lipid Research Clinics Coronary Primary Prevention Trial Multiple Risk Factor Intervention Trial for the Prevention of Coronary Heart Disease Hypertension Detection and Follow-Up Program Unstable Angina Pectoris Trial Coronary Artery Surgery Study Program on Surgical Control of Hyperlipidemias Aspirin-Myocardial Infarction Study Beta-Blocker Heart Attack Trial Multicenter Investigation of Limitation of Infarct Size Treatment of Hypertension Management of Patent Ductus in Premature Infants Systolic Hypertension in the Elderly Program (Pilot Study) Randomized Trial of Aspirin and Mortality in Physicians Hypertension Prevention Trial Cardiac Arrhythmia Pilot Study Randomized Clinical Trial of Non-Surgical Reperfusion of the Coronary Arteries Thrombolysis in Myocardial Infarction Dietary Intervention Study for Hypertension Control of Hypertension by Non-Pharmacologic Means Risk Factor Intervention in Coronary Disease Intravenous Streptokinase in Acute Myocardial Infarction Platelet Drug Trial in Coronary Disease Progression Platelet-Inhibitor Drug Trial in Coronary Angioplasty Evaluation of SC-V Versus Conventional CPR Systolic Hypertension in the Elderly Program Studies of Left Ventricular Dysfunction Lung Diseases Program Prevention of Neonatal Respiratory Distress Syndrome with Antenatal Steroid Administration Clinical Study of Intermittent Positive Pressure Breathing Nocturnal Oxygen Therapy Extracorporeal Support for Respiratory Insufficiency Prospective Investigation of Pulmonary Embolism Diagnosis Prevention of Chronic Obstructive Pulmonary Disease High Frequency Ventilation in Premature Infants Blood Diseases and Resources Program Granulocyte Transfusion Study Interruption of Maternal-to-Infant Transmission of Hepatitis B by Means of Hepatitis B Immune Globulin Cooperative Study of Factor VIII Inhibitors Hepatitis B Vaccine Clinical Trial Transfusion-Transmitted Cytomegalovirus Prevention in Neonates Division of Intramural Research NHLBI Type II Coronary Intervention Study Diffuse Fibrotic Lung Disease Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis and a Controlled Trial to Determine the Value of Supplemental Ascorbic Acid 1965/18 1981/3.5 1973/15 1972/13 1971/14 1972/10 1973/14 1973/12 1974/6 1977/7 1977/8 1966/12 1978/4 1980/5 1981/9 1981/5 1982/5 1982/5 1983/4 1980/3 1980/5 1983/5 1983/4 1979/8 1983/5 1981/3 1984/9 1985/5 1976/7 1976/7 1976/4 1974/3 1983/5 1984/7.5 1984/3 1976/4 1975/3 1978/2 1978/3 1983/3 1971/10 1978/5 41.6 0.2 172.0 115.3 71.6 0.6 26.9 51.1 16.9 18.4 19.0 3.1 4.3 3.7 8.0 10.6 7.9 4.2 10.2 10.2 2.3 2.9 1.3 1.9 1.6 0.9 48.0 30.1 5.5 8.9 4.0 5.6 7.6 20.9 7.0 1.6 0.1 0.8 0.2 0.7 0.5 69.1 man-years 1978/5 13.5 man-years a Total duration, including patient recruitment, intervention, analysis, follow-up.

APPENDIX A: PROFILES the initiation year, duration, and actual or projected total cost of each. Other assessment topics are addressed in group efforts such as consensus development conferences, special task forces and other working groups, and in state-of-the-art review articles. Many of the group efforts are cosponsored by other fed- eral agencies and by professional and volun- tary organizations. NHLBI has cosponsored with the NIH Office of Medical Applications of Research (OMAR) the following eight NIH consensus development conferences: · Tranfusion Therapy in Pregnant Sickle Cell Disease Patients (1979) · Improving Clinical and Consumer Blood Pressure Measuring Devices (1979) · Thrombolytic Therapy in Thrombosis (1980) · Coronary Bypass Surgery (1980) (A sec- ond conference was cosponsored with the National Center for Health Care Technol- ogy) · Treatment of Hypertriglyceridemias (1983) · Fresh Frozen Plasma: Indications and Risks (1984) · Lowering Blood Cholesterol to Prevent Heart Disease (1984) · Health Implications of Obesity (1985~. The following are examples of publications covering other recent group efforts con- ducted or cosponsored by NHLBI on subjects related to technology assessment. · Fourteenth Bethesda Conference: Non- invasive Diagnostic Instrumentation for As- sessment of Cardiovascular Diseases in the Young · Third Report of the Joint National Com- mittee on the Detection, Evaluation, and Treatment of High Blood Pressure · Proceedings of a Workshop on Apolipo- protein Qualification · Report of the Working Group to Define Critical Behaviors in the Dietary Manage- ment of High Blood Pressure · Working Papers, NHLBI Conference on the Implications of the Hypertension Detec- tion and Followup Program · Workshop on Arachidonic Acid Metabo- lism and the Pulmonary Circulation 377 · Report of the Working Group on Arteri- osclerosis of the National Heart, Lung, and Blood Institute · Artificial Heart and Assist Devices: Di- rections, Needs, Costs, Societal and Ethical Issues. Report of the Working Group on Me- chanical Circulatory Support of the National Heart, Lung, and Blood Institute · Legal and Ethical Issues Surrounding Organ Transplantation Through OMAR, NHLBI participates in the technology coverage decision process for the Health Care Financing Administration (HCFA). In FY 1983 and 1984, OMAR re- ferred 22 HCFA coverage issues to NHLBI for review and analysis. Examples of technol- ogies that were subjects of these inquiries are outpatient cardiac catheterization, cardiac pacemakers, fully automated blood pressure monitoring, and streptokinase infusion for acute myocardial infarction. (The profile of OMAR describes the NIH Consensus Development Program in detail and OMAR's role in coordinating NIH re- sponses to HCFA inquiries. See the Office of Health Technology Assessment tOHTA] pro- file for discussion of its role in coordinating Public Health Service responses to HCFA . . . ~ coverage Inquiries.) Stage of Diffusion NHLBI's technology assessment activities address emerging and new technologies and established technologies in transition. Ac- cording to the institute, emerging technolo- gies are those under development that appear likely to be used in the practice of medicine within 5 years. New technologies are those that may have passed the stage of clinical trials but are not yet widely disseminated, or those that are moving into general use with- out benefit of clinical trials. The last group are those established technologies that are currently undergoing or likely to undergo major changes in use or costs as a result of new research findings, or for which serious concerns have been raised concerning safety and effectiveness. Examples of clinical trials involving established technologies in transi- tion are the Coronary Artery Surgery Study

378 and the Clinical Study of Intermittent Posi- tive Pressure Breathing. Concerns ASSESSING MEDICAL TECHNOLOGY Of the 43 NHLBI clinical trials initiated since 1965, 17 have been funded by grants, 22 by contract, 2 were intramural studies, and the others were combinations of these. Clinical trials account for a minority of all NIH grants and contracts, which are also The principal concerns of NHLBI assess- ment activities are safety and efficacy. The provided for laboratory research and other institute also continues to address certain R&D activities. (The definition and use of ethical, social, and legal implications of tech- .1 . 7. ~ my, ~ 7 · STATE 1 nologies such as the artificial heart and ven- tricular assist devices, coronary artery bypass surgery, and organ transplantation. (Exam- ples are the efforts of the NHLBI Working Group on Mechanical Circulatory Support, and the 1985 conference cosponsored by the institute on the legal and ethical issues sur- rounding organ transplantation.) Of course, the planning and conduct of research sup- ported by NHLBI—particularly clinical trials are subject to detailed review of ethi- cal considerations. The institute does con- duct some cost studies, such as in-house stud- ies to demonstrate the cost-effectiveness of its clinical trials. It must also evaluate the cost- effectiveness of the federal investment in the National Heart, Blood Vessel, Lung, and Blood Program, and make recommendations regarding future resource allocations. Requests (The descriptions under Requests, Selec- tion, and Process address N[ILBI clinical trials. Other assessment activities conducted by NHLBI, i.e., consensus development con- ferences and the technology coverage deci- sion process for HCFA, are described in the profiles of OMAR and OHTA.) The process of initiating a clinical trial begins with dis- cussions among institute staff, institute advi- sory groups, and other biomedical scientists and health care researchers. Suggestions may also originate from workshops, conferences, and various professional organizations. In most cases, a clinical trial is part of the pro- gression of an idea as it emerges from basic science through clinical research to the point at which large-scale testing is required to de- termine the safety and efficacy of a technol- ogy. Activities leading up to a clinical trial frequently include feasibility studies and pi- lot studies of intervention. the term clinical trial varies among Ally bu- reaus, institutes, and divisions. NIH is con- sidering the implementation of a standard- ized inventory of clinical trials that will use common definitions of this and related terms. ~ Most grants are not solicited by the insti- tute. In general, the investigator (through an eligible institution) who applies for a grant is formally responsible for developing the ideas, concepts, methods, and approach for a re- search project. In contrast, for projects that would be supported by contracts, the insti- tute is responsible for establishing the plans, parameters, and detailed requirements. Con- tracts are generally solicited through requests for proposals (RFPs). In certain circum- stances, grant applications are invited to sup- port areas of special interest to the institute, in which case requests for applications (RFAs) and program announcements are is- sued. For solicited contracts, institute advisory groups generally recommend types of proj- ects that should be undertaken by the respec- tive institutes. In NHLBI, these groups in- clude the Arteriosclerosis, Hypertension and Lipid Metabolism Advisory Committee; Blood Diseases and Resources Advisory Com- mittee; Cardiology Advisory Committee; - (:linical Applicat~ons and Prevention Advi- sory Committee; Pulmonary Diseases Advi- sory Committee; and Sickle Cell Disease Ad- visory Committee. The institute advisory groups review the contract concept to recom- mend whether the anticipated results will be beneficial to NIH and whether the necessary technology and resources are available. If the contract concept is approved by the institute, an REP is prepared and advertised. The REP defines the program requirements and de- scribes the.criteria by which the proposals will be evaluated.

APPENDIX A: PROFILES Selection 379 is undertaken by panels of experts- referred to as study sections established by the Divi- Proposed clinical trials generally go sion of Research Grants according to scien- through a peer review process twice—the tific disciplines or current research areas for first time for approval to plan the trial and the primary purpose of evaluating the scien- develop a detailed trial protocol; the second tific and technical merit of grant applica- time for review of the detailed proposals for - A' ' ^~ - conducting the trial. Review of a proposal to plan a trial entails consideration of the state of the science, feasi- bility, required resources, potential impact, and ethical considerations. Approval com- mits resources to plan the trial and develop its protocol. This approval does not commit NHLBI to conduct the trial itself, although its fiscal planning is made with the assump- tion that the planning phase will develop a scientifically appropriate and feasible proto- col. Once a proposal to plan a trial is ap- proved, a planning committee composed of principal investigators and other key project staff and institute staff oversees a detailed trial planning process generally involving subcommittees on trial design, patient eligi- bility, pharmacology, end points, recruit- ment, and others as appropriate. The major factors considered in review of a proposal to conduct a trial are the feasibility of the trial based on the detailed planning, the state of the science, and the projected cost of the trial. Although these have been re- viewed earlier in the decision to approve planning of the trial, they are considered in great detail here. Approval to conduct the trial commits defined resources for an ex- tended period—several years in the case of major long-term trials. (For an example of a detailed clinical trial protocol, see NHLBI t19783.) The peer review system for grant applica- tions used by the NIH is based on two sequen- tial levels of review, referred to as the dual review system. The dual review system is in- tended to separate the scientific assessment of proposed projects from policy decisions about scientific areas to be supported and the level of resources to be allocated. Grant applica- tions submitted to NIH are received and pro- cessed centrally by the Division of Research Grants, which is one of the research and sup- port divisions of NIlI. For most institutes, the first level of review tions. There are approximately 95 study sec- tions in the Division of Research Grants. In the case of NHLBI, the Division of Research Grants also may forward grant applications to the NHLBI Division of Extramural Af- fairs, which establishes ad hoc study sections to carry out the first level of review. (This is usually the case for program project grants and institute-solicited programs, including clinical trials.) These study sections usually consist of 12 to 20 members each and are composed primarily of nonfederal scientists selected for their competence in the particu- lar scientific areas for which that study sec- tion has review responsibilities. An NIH health scientist administrator serves as execu- tive secretary of each study section. The study sections provide initial scientific and technical merit review of grant applications, but they make no funding decisions and do not set program priorities. The study sections may recommend that a grant application be approved, disapproved, or deferred for fur- ther information. For approved applications, they assign a technical merit priority rating and make specific budget recommendations. The second level of review is conducted by the institute and includes review by appro- priate division staff, the institute director, and a national advisory board or council of the institute. For NHLBI, this is the National Heart, Lung, and Blood Advisory Council. Council recommendations are based not only on considerations of scientific merit, as judged by the study sections, but also on the relevance of the proposed study, as outlined in a grant application, to the institute's pro- grams and priorities. The council assesses the quality of study section review of grant appli- cations, makes recommendations to institute staff on funding, and evaluates program pri- orities and relevance. It also advises on policy and matters of significance to the mission and goals of the institute. Variations on this process are required for review of solicited and unsolicited contract

380 proposals and for proposals responding to so- licitations for R&D support. All of these re- view, approval, and award processes are con- ducted in accordance with requirements of federal and DHHS procurement regulations. Process If the institute makes a commitment to conduct a trial, subject recruitment and clin- ical intervention begin. In general, subjects are not recruited simultaneously, and thus the recruitment and intervention activities proceed together. Once the trial is under way, it is managed by a complex of committees composed of the investigators, advisors, and institute staff. Often, the central organizational element of the trial is a steering committee that provides overall scientific direction for the study at the operational level. Various subcommittees ap- pointed by the steering committee are re- sponsible for reviewing such matters as pa- tient adherence, quality control, nonfatal events, natural history, mortality classifica- tion, bibliography, and editorial review. An assembly of investigators representing all of the clinical and logistical coordinating cen- ters reports to the steering committee. A pol- icy data-monitoring board which does not in- clude any of the trial investigators acts in a senior advisory capacity to NHLBI on policy matters throughout the duration of the trial. It periodically reviews study results and eval- uates the study treatments for beneficial and adverse effects, and consults on such major policy decisions as trial safety and termina- tion, changes in protocol, measurement pro- cedures, and publication. Analysis continues during the trial. By the time the trial is ended, much of the analysis concerning the major question may already have been completed. However, only in rare cases such as those in which a trial is not double-blind and the trends are extraordi- nary might the findings of a trial be pub- lished during its course. Assessors NHLBI technology assessment activities entail the participation of the full comple- ASSESSING MEDICAL TECHNOLOGY ment of biomedical research and health care delivery personnel. Various advisory groups also include representatives of other profes- sions. As noted above, members of the Na- tional Heart, Lung, and Blood Advisory Council include scientists and others who are lay community members with a demon- strated interest in health areas relevant to the program area of the institute. The study sec- tions that review proposals are composed of nonfederal scientists selected for their compe- tence in the particular scientific areas for which a study section has review responsibili- ties. Turnaround The duration of clinical trials supported by NHLBI has ranged from 2 to 18 years (in- cluding patient follow-up), averaging about 6.6 years, although interim assessments and other reports are made during the longer trials. Consensus conferences, state-of-the- art conferences, and workshops generally take about 1 year to plan. Reporting Reports of NHLBI clinical trials and other assessment activities appear in many medical and other scientific journals; books; technical reports; conference proceedings; annual re- ports of the National Heart, Lung, and Blood Advisory Council; and reports from the di- rectors of NIH and NHLBI, and OMAR. For example, reports of the 13-year Multiple Risk Factor Intervention Trial for the Prevention of Coronary Heart Disease (MRFIT) have appeared in the American Journal of Epide- miology, American Journal of Medicine, American Journal of Public Health, Annals of the New York Academy of Sciences, Circu- lation, International Journal of Mental Health, Journal of the American Dietetic As- sociation, Journal of the American Medical Association, Journal of Chronic Diseases, Preventive Medicine, and various NIH re- ports and conference proceedings. Among the other journals in which NHLBI assessment activities are often reported are the American Heart Journal, American Jour- nal of Cardiology, Annals of Internal Medi-

APPENDIX A: PROFILES cine, Chest, Circulation Research, Hyper- tension, Controlled Clinical Trials, Journal of the American College of Cardiology, lour- nal o; Community Health, Journal of Medi- cal Virology, Medical Care, New England Journal of Medicine, and Symposia Reporter. NHLBI promotes and disseminates assess- ment findings through workshops; informa- tion centers; and prevention, education, and control programs. The institute also dissemi- nates information through professional soci- eties, educational programs such as the Na- tional High Blood Pressure Education Program, clearinghouses such as the High Blood Pressure Information Center, interac- tions with industry representatives, and ac- tivities of the institute's Office of Prevention, Education, and Control. NHLBI's Specialized Centers of Research (SCORs) and National Research and Demon- stration Centers Program are important means of technology transfer. SCORs were initiated to provide a program of basic and clinical research in institutions that are fully equipped and staffed to support sophisticated investigations of specific diseases. Impact NHLBI is the leading research organiza- tion addressing cardiovascular, pulmonary, and hematologic diseases. There has been a concurrent expansion of NHLBI's functions and funding, and the sharp decline in adult cardiovascular mortality in the United States. Over the 20-year period 1963 to 1983, the death rates for coronary heart disease and cerebrovascular disease dropped 40 and 55 percent, respectively. The death rate for all cardiovascular diseases combined declined much more rapidly over that period than did the rate for all other causes of death com- bined. The decline in the death rate from coronary heart disease has resulted in the pre- vention of an estimated 114,000 deaths annu- ally. Improvements in rates of mortality and morbidity are not only desirable for human well-being, but there are also sizeable eco- nomic benefits. The decrease in mortality from cardiovascular disease has been attrib- uted to advances in diagnosis and treatment 381 (e. g., early noninvasive diagnostic tech- niques and coronary care units), preventive measures, and changes in life-style. Among 26 industrialized countries, the United States has shown the steepest decline in cardiovas- cular mortality in middle-aged men, and the steepest decline in mortality from coronary heart disease in men and women ages 35-74 years. Over the last generation, no advance in the prevention, diagnosis, or treatment of dis- eases of the heart and blood vessels, the lungs, and the blood has been unaffected in some measure by NHLBI, and most major technological advances in these areas have come as a direct result of NHLBI support. These have certainly resulted in improve- ment in the health of the American people and others throughout the world. However, it is not possible to quantify causal connec- tions between the wide spectrum of NHLBI activities and improvements in the health of the American people. According to the institute, a number of NHLBI clinical trials have had major impli- cations for practice, including the following. · The Beta-Blocker Heart Attack Trial to determine whether the regular administra- tion of propranolol would prevent sudden death in patients with myocardial infarction. In this trial, mortality in patients on pro- pranolol was reduced 26 percent (from 9.8 to 7.2 percent) when compared to the control group. This would amount to a savings of at least 6,000 lives annually if put into wide- spread practice. · The Coronary Primary Prevention Trial showed that lowering blood cholesterol re- duces risk of coronary heart disease. The results of this trial have immediate applica- bility to the estimated one to two million hy- percholesterolemic men in the country, and the results could be extended to women with elevated cholesterol levels. · The implications of the Coronary Artery Surgery Study, which compared surgical and medical treatment of patients with mild to moderate heart pain or in those who survived a heart attack and were free of angina, are that mildly affected patients can be managed with medical rather than surgical treatment

382 unless or until the condition becomes worse and surgery is clearly indicated. Results of this trial should make it possible to select pa- tients for bypass surgery more appropriately. · The Type II Coronary Intervention Study of the effects of diet and drug therapy on the rate of progression of coronary heart disease showed that the greater the reduction in cholesterol obtained through treatment, the less the progression of coronary artery dis- ease. · The Intermittent Positive Pressure Breathing (IPPB) Study provided scientific evidence to the medical community that IPPB provides no benefit as a therapy for am- bulatory patients with chronic obstructive pulmonary disease. NHLBI also evaluates its technology trans- fer and information dissemination processes, e.g., the Evaluation of Health Hazard Ap- praisal Strategies in Industrial Cardiovascu- lar Risk Reduction Programs, and the Evalu- ation of Sickle Cell Education. OMAR has conducted and sponsored evaluations of the NIH Consensus Development Program, which has included consensus conferences cosponsored by NHLBI. Reassessment NHLBI reassesses technologies in light of new scientific evidence of efficacy or of long- term adverse effects not apparent in short- term studies, and given suggested new uses for established technologies. Two examples of such reassessment are the reappraisals of arteriosclerosis and the institute's artificial heart program. NHLBI sponsored expert panel reports in 1971, 1978, and 1981 on arteriosclerosis. The first task group on arteriosclerosis was formed in response to the magnitude of the national and personal toll exacted by the dis- ease, and issued its report in 1971. This re- port was instrumental in the passage of the National Heart, Blood Vessel, Lung, and Blood Act of 1972. The 1981 report of this group summarized the current understand- ing of basic processes of the disease; its pre- vention, diagnosis, and treatment; and reha- bilitation of persons suffering from it. It also ASSESSING MEDICAL TECHNOLOGY identified opportunities for research, with particular attention to preventive measures, therapies, and technologies ready for clinical trials or application in practice. The institute's artificial heart program, formally established in 1964, has evolved during a period characterized by marked changes in technology; cost considerations; and ethical, legal, and social concerns rele- vant to the program. The institute has spon- sored periodic reviews of the artificial heart program, reports of which were published in 1969, 1973, 1977, 1980, 1981, and most re- cently in 1985 by the NHLBI Working Group on Mechanical Circulatory Support. Funding/Budget NIH is funded by congressional appropria- tion. In terms of appropriations, NHLBI is the second largest institute after the National Cancer Institute (NCI). In FY 1984, NHLBI appropriations were $703.2 million, or nearly 16 percent of the total NIH appropria- tions. In constant dollars, NHLBI funding rose during the 1970s, but was reduced by 1982 to 85 percent of its 1979 level. By FY 1984, it had risen again to nearly the 1979 level. NHLBI funding is broken down by pro- gram areas roughly as follows: heart and vas- cular diseases (67 percent), lung diseases (17 percent), and blood diseases and resources (16 percent). By type of activity, funding consists of extramural research (86 percent), intramural research (8 percent), direct oper- ations (5 percent), and program manage- ment (1 percent). Clinical trials expenditures by NHLBI were $22.9 million in FY 1984 and an esti- mated $25.2 million in FY 1985, accounting for about 9 percent of total NIH clinical trials expenditures. (Total NIH clinical trials ex- penditures are an estimated $275.7 million for FY 1985, of which NCI accounts for 59 percent. ~ Due to uncertainties in funding and competing priorities, NHLBI has postponed initiating new large-scale clinical trials since 1978; its support of clinical trials overall dropped from the $40 million-$60 million range of the mid- to late 1970s to $25.2 mil- lion in FY 1985 (current dollars not corrected

APPENDIX A: PROFILES for inflation). Whereas clinical trials expend- itures accounted for 11 percent of NHLBI ex- penditures in 1979, they accounted for only 3.2 percent of 1984 NHLBI expenditures. Example On the following pages is a brief descrip- tion of the Coronary Artery Surgery Study, a major long-term trial supported by NHLBI comparing surgical and medical treatment of coronary heart disease. This description is given in the May 1984 NHLBI Clinical Trials Reference Document, as updated in June 1985. Sources DeMets, D. L., R. Hardy, L. M. Friedman, and K. K. Gordon. 1984. Statistical aspects of early termina- tion in the beta-blocker heart attack trial. Controlled Clinical Trials 5:362-372. Levy, R. I., and J. Moskowitz. 1982. Cardiovascu- lar research: Decades of progress, a decade of prom- ise. Science 217: 121-129. Levy, R. I., and E. J. Sondik. 1978. Decision-mak- ing in planning large-scale comparative studies. An- nals of the New York Academy of Sciences 304:441- 457. Moskowitz, J., Director, Office of Program Plan- ning and Evaluation, National Heart, Lung, and Blood Institute. 1985. Personal communication. Assis- tance was also provided by W. T. Friedewald, Direc- tor of the Division of Epidemiology and Clinical Ap- plications, NHLBI; L. M. Friedman, Chief, Clinical Trials Branch, Division of Epidemiology and Clinical Applications, NHLBI; P. L. Frommer, Deputy Direc- tor, NHLBI; and J. G. Green, Director of Extramural Affairs, NHLBI. Moskowitz, J., S. N. Finkelstein, R.I. Levy, et al. 1981. Biomedical innovation: The challenge and the process. In E. B. Roberts, R. I. Levy, S. N. Finkel- stein, et al. (eds). Biomedical Innovation. Cam- bridge, Mass.: MIT Press. National Heart, Lung, and Blood Institute. 1978. 383 Beta-Blocker Heart Attack Trial Study Protocol (with July 1980 update). Bethesda, Md. National Heart, Lung, and Blood Institute. 1982. Tenth Report of the Director, National Heart, Lung, Blood Institute. Volume 1: Progress and Promise. Be- thesda, Md. National Heart, Lung, and Blood Institute. 1983. Guidelines for Demonstration and Education Re- search Grants. Bethesda, Md. National Heart, Lung, and Blood Institute. 1983. Eleventh Report of the National Heart, Lung, and Blood Advisory Council. Bethesda, Md. National Heart, Lung, and Blood Institute. 1984. Clinical Trials Reference Document. Bethesda, Md. National Heart, Lung, and Blood Institute. 1984. Fiscal Year 1984 Fact Book. Bethesda, Md. National Heart, Lung, and Blood Institute Work- ing Group on Arteriosclerosis. 1981. Arteriosclerosis 1981. Volume 1: Summary, Conclusions, and Recom- mendations. Bethesda, Md. National Heart, Lung, and Blood Institute Work- ing Group on Mechanical Circulatory Support. 1985. Artificial Heart and Assist Devices: Directions, Needs, Costs, Societal and Ethical Issues. Bethesda, Md. National Institutes of Health. 1982. Orientation Handbook for Members of Scientific Review Groups. Bethesda, Md. National Institutes of Health. 1983. NIH Public Advisory Groups: Authority, Structure, Functions, Members. Bethesda, Md. National Institutes of Health. 1983. National Insti- tutes of Health Organization Handbook. Bethesda, Md. National Institutes of Health. 1984. NIH Data Book. Bethesda, Md. National Institutes of Health. 1985. Report on the Patterns of Funding Clinical Research. Bethesda, Md. Office of Medical Applications of Research, Na- tional Institutes of Health. 1984. Technology Assess- ment and Technology Transfer in DHHS: A Report Submitted to the Department of Commerce in Com- pliance with the Stevenson-Wydler Technology Inno- vation Act of 1980 (P.L. 96-480~. Bethesda, Md. Office of Technology Assessment. 1982. Technol- ogy Transfer at the National Institutes of Health. Washington, D.C.: U.S. Government Printing Of- fice.

384 ASSESSING MEDICAL TECHNOLOGY CORONARY ARTERY SURGERY STUDY (CASS) Objective To compare coronary artery surgery with medical management in patients with coro- nary artery disease and to maintain a registry on all patients undergoing coronary arteriog- raphy, whether operatively or medically managed. Summary Data Mechanism: Initiation: Total Duration: Funding: Contract June 1973 14 years Total funding prior to FY 1984 FY 1984 support Support projected beyond FY 1984 Total support Subjects $23,958,615 2,924,971 $26,883,586 Randomized: males and females, under 66 years of age with ischemic heart disease and specific history, symptoms, and angiographic findings. Registry: All patients undergoing coronary angiography for ischemic heart disease. Experimental Design Randomized: non-blind, sequential. Some 780 patients meeting the criteria of specific subsets based on history, physical exam, lab- oratory tests, catheterization, and angiogra- phy were randomized to either surgical or medical therapy. Primary endpoints in- cluded death and myocardial infarction. Registry: Essentially identical data, but no randomization. Current Phase (As of June 1985~: Analysis and dissemina- tion. Background Although it is generally agreed that many patients with severe angina pectoris improve symptomatically after coronary artery sur- gery, there is less consensus concerning, for example, other effects of the procedure, such as its long-term benefit and the criteria for patient selection. In addition, there are fewer data and less agreement on the effects and proper role of this procedure in other clinical circumstances. Both the surgical procedure and the prior diagnostic procedures represent substantial costs in both monetary and man- power terms; moreover, they entail morbid- ity and mortality risks. There exists an urgent need for reliable and quantitative information regarding the ef- fects of coronary artery surgery in patients 0 with coronary ischemic heart disease. To be meaningful, these data must be set into the perspective of the clinical course of such pa- tients under medical treatment. This assess- ment presupposes a meaningful classification of these patients and of the therapeutic inter- ventions as well as evaluations of the effects of surgical and medical regimens in terms of mortality, the quality of life, and objective hemodynamic and other physiological mea- surements. Only such information can pro- vide sufficient background for determining the suitability of coronary artery surgery for a particular patient. In 1972, the National Heart and Lung Ad- visory Council identified these questions as topics of high priority, and the National Heart and Lung Institute established an Ad Hoc Policy Advisory Board on Coronary Ar- tery Surgery to assist it in developing a pro- ~ram of research activities. In its report, the board noted a "critical need for objective data on the long- and short-term effects of coronary artery surgery." Requests for pro- posals were issued to carry out the recom- mendations of the board. Planning of the trial was conducted be- tween June 1973 and April 1975 and included protocol design, the development of a man- ual of operations, and a pilot study of the reg- istry. In August 1975, registry patients' entry

. APPENDIX A: PROFILES and randomization began at the 11 clinical centers and coordinating center. Initial pro- jections of patient population numbers were underestimated, therefore, five clinical cen- ters were added to the trial in 1976. The five clinical subgroups of patients in the randomized studies included stable an- gina with normal resting left ventricular function; stable angina with impaired left ventricular function; postmyocardial infarc- tion without angina; congestive heart failure due primarily to ischemic heart disease; and patients previously asymptomatic who were discovered to have serious coronary artery disease. All of the above subgroups must have met specifically outlined clinical and angio- graphic criteria to be placed in the random- ized subset. The other two subsets (as distin- guished from subgroups) of the study included those patients who were unsuitable for randomization because surgery was the treatment of choice in the judgment of many physicians and those patients for whom med- ical management was the treatment of choice. The patients enrolled in both the reg- istry and randomized trial were followed for a 10-year period. This allowed evaluation of the primary endpoints, death and myocar- dial infarctions, and the secondary end- points, angina, status, and quality of life. A total of 24,959 patients were entered into the registry; 780 patients were entered into the trial. Recruitment ended in 1979. In- tervention ended in June 1983. Follow-up has been extended for an additional four years to 1988. Trial Results The randomized collaborative Coronary Artery Surgery Study showed that coronary artery bypass graft surgery improves the quality-of-life as manifested by relief of chest pain, by improvement in both subjective and objective measurements of functional status, and by a diminished requirement for phar- macological therapy. However, no signifi- cant effect on employment or recreational status was observed. The excellent survival observed in both medically and surgically as- signed CASS patients and the similarity of survival rates in groups of patients assigned to 385 either treatment strategy . . . . . . . i] n this randomized trial leads to the conclusion that patients sim- ilar to those enrolled in this trial can safely defer bypass surgery until worsening symp- toms require surgical palliation. From August 1975 to May 1979, 780 pa- tients with stable moderate or milder ische- mic heart disease were randomly assigned to surgical (390) or nonsurgical (390) manage- ment and followed through April 15, 1983. At five years, the average annual mortality rate in patients assigned to surgery was l.l~o. The annual mortality rate in those randomized to medicine was 1.6%. The an- nual mortality rates in surgically assigned pa- tients with single, double, and triple vessel disease were 0.7 %, 1.0 %, and 1.5 %; the corresponding rates in medically assigned pa- tients were 1.4 %, 1.2 %, and 2.1 % . None of the differences were statistically significant. The annual rate of bypass surgery in all medi- cally assigned patients was 4.7 % . In order to evaluate the comparative ef- fects of medical and surgical therapy on "quality-of-life" in patients with stable mani- festations of ischemic heart disease, the 780 randomized patients were systematically fol- lowed for a mean of 5.5 years. Analysis was performed according to original treatment assignment. Surgically assigned patients had significantly less chest pain, fewer activity limitations, and less utilization of nitrates and beta-blockers. Treadmill exercise tests documented significantly longer treadmill time, less exercise-induced angina, and less ST-segment depression among surgical pa- tients. However, employment status and rec- reational status did not differ significantly between medical and surgical groups, al- though employment status related signifi- cantly to chest pain severity. Total hospital- izations following randomization were greater in the surgical group owing primarily to rehospitalization during the first year of follow-up for the coronary artery bypass graft surgical procedure.

Consensus Development Program Office of Medical Applications of Research National Institutes of Health Building I, Room 216 Bethesda, MD 20205 (301) 496 I 143 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X X X Ethical/Legal/ S., octal X Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded Application of Technologies X Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials Epidemiological and other observational methods Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $1,789,000* * This is the approximate total OMAR budget for 1985. The average total cost of a consensus conference is approximately $145,000. OFFICE OF MEDICAL APPLICATIONS OF RESEARCH NATIONAL INSTITUTES OF HEALTH Introduction The Office of Medical Applications of Re- search (OMAR) was informally established in 1977 with the initiation of the Consensus De- velopment Program, and was formally estab- lished in the Office of the Director of NIH in 1978. OMAR is the focal point for activities aimed at improving the assessment and trans- 386 ration of results from NIH-supported bio- medical research into knowledge that can be applied safely and effectively in the practice of medicine and public health. OMAR's functions, as published in the Federal Regis- ter of October 13, 1978, may be summarized as follows (OMAR, 1983a). · Advise the NIH director and his senior staff, and provide guidance to the NIH Bu- reaus, Institutes, and Divisions (BIDs) on medical applications of research. · Coordinate, review, and facilitate the

APPENDIX A: PROFILES systematic identification and evaluation of clinically relevant NIH program informa- tion. · Promote the effective transfer of such in- formation to the health care community and to other agencies requiring such information. · Provide a link between technology as- sessment activities for the BIDs and the Of- fice of Health Technology Assessment (OHTA) of the National Center for Health Services Research (NCHSR). · Monitor the effectiveness and progress of NIH assessment and transfer activities. A primary vehicle for OMAR's efforts in systematic assessment of biomedical technol- ogies is the Consensus Development Program (CDP). Each CDP conference is a coopera- tive effort of OMAR and one or more BID co- sponsors. Other OMAR technology assess- ment and transfer activities include the following. Administration of the NIH/DHHS Patent Program The NIH/DHHS patent program fosters commercialization of federally funded inventions. The director of NIH designated OMAR to act as the central clearinghouse for all NIH patent-related activities. The direc- tor of OMAR also serves as chairperson of the NIH Patent Board. Review and Analysis of HCFA Medicare Coverage Questions OMAR coordinates NIH medical and scientific review of the Health Care Financing Administration (HCFA) Medicare coverage issues referred to NIH by the Office of Health Technology As- sessment of the National Center for Health Services Research and Health Care Technol- ogy Assessment (NCHSRHCTA). During FY 1981 and 1982, OMAR coordinated the as- sessment of nearly 100 HCFA Medicare cov- erage issues raised by Medicare contractors, practitioners, private industry, and others. Depending upon the nature of the specific technology in question, the coverage issue is forwarded by OMAR to one or more appro- priate BIDs. OMAR reviews and integrates the BID responses and forwards them to OHTA. 387 Research and Evaluation Activities OMAR undertakes and awards contracts for special studies to evaluate and improve as- sessment and transfer efforts. Studies in FY 1981 and 1982 have included evaluations of · the impact of discoveries in biomedical research that have been adopted by industry for commercial application outside the health-care sector; · the NIH/DHHS Patent Program; · physician awareness of the Consensus Development Program; and · the process and the impact on health practice behavior of the Consensus Develop- ment Program and possible alternative ap- proaches for biomedical technology assess- ment and transfer. NIH Coordinating Committee on Assess- ment and Transfer of Technology The di- rector of OMAR serves as chairperson of the NIH Coordinating Committee on Assessment and Transfer of Technology, established by the director of NIH to provide a mechanism for the coordination of NIH policy and activi- ties related to health technology assessment and transfer. The committee is composed of one representative from each of the BIDs. Li- aison representatives from ADAMHA, FDA, CDC, OHTA, NCHSRHCTA, NCHS, and the DHHS Office of the Assistant Secretary for Health also participate. The remainder of this profile addresses the NIH Consensus Development Program, which is coordinated by OMAR. Purpose The purpose of the CDP is to evaluate pub- licly scientific information concerning bio- medical technologies and arrive at consensus statements that will be useful to health care providers and the public at large and that will serve as contributions to scientific think- ing about the technologies under consider- ation (OMAR, Participants' Guide). The CDP has three primary objectives: 1. to provide a setting for the evaluation and review of the scientific soundness of a health or health-related technology, with emphasis on safety and efficacy;

388 2. to aid in the diffusion of knowledge of advances in biomedical technology, through dissemination of the findings from the con- sensus development process to physicians and consumers; and 3. to facilitate the diffusion, adoption, and appropriate use of technologies found to be sound. It is intended that as a result of the Consensus Development evalu- ations . . . the use of those technologies found to be scientifically sound will increase and those that receive no such endorsement will diminish, thus adding something to the quality of health care (NIH, 1980~. The CDP is not meant to dictate the prac- tice of medicine. Rather than being guide- lines or regulations, consensus statements are intended to aid the physician and the public, and to be influential by weight of the prestige of the consensus process and the members of the panel (Iacoby, 1983~. The consensus statement is an independent report and is not a policy statement of NIH or the federal gov- ernment. Subjects of Assessment A broad variety of technologies have been topics of consensus conferences, including medical and dental drugs, devices, proce- dures, facilities, and support systems used in prevention, diagnosis, and treatment. Table A-ll lists the CDP conferences held since the program's inception in 1977. Stage of Diffusion Although the CDP originally was to have focused on emerging technologies, most of the conferences have addressed technologies already in clinical use, especially new or widely used technologies. This is largely be- cause evaluative information regarding many emerging technologies is insufficient for the level of validity sought for CDP con- ferences, and because many technologies al- ready in widespread use have not been care- fully scrutinized for safety and efficacy (Iacoby, 1984; Perry and Kalberer, 1980~. ASSESSING MEDICAL TECHNOLOGY Concerns The CDP is primarily concerned with the safety, efficacy, and clinical application of technologies. It does not normally address so- cial, ethical, legal, economic, or political is- sues surrounding technologies. At the time of the establishment of OMAR, NIH identified two types of consensus devel- opment: technical consensus development, the assessment of the scientific and medical aspects of the technology in question, and in- terface consensus development, the assess- ment of the economic, social, legal, and ethi- cal implications as well as the scientific and medical issues (NIH, 1977~. In these terms, the CDP involves technical consensus devel- opment. The focus of each consensus conference is established by a set of predetermined ques- tions. The questions identify the relevant is- sues and define the scope of the conference. These questions, the answers as determined by the consensus panel, and a conclusion comprise the final consensus statement. As discussed below under Process, program planning committees composed of NIH staff and outside experts cooperate with OMAR in posing and editing conference questions. Ex- amples of CDP conference questions are shown in Table A-12. Requests Suggestions for consensus conferences come from many sources, including the staff or director of a sponsoring NIH BID, OMAR staff, the director of NIH, consumer groups, government agencies such as HCFA, or Con- gress. Requests may coincide with the plan- ning or completion of a major clinical trial. Selection Although the criteria for selecting topics for consensus development conferences have varied somewhat since the program's incep- tion, current criteria are as follows. 1. The subject under consideration should be medically important. 2. There should be a scientific controversy

APPENDIX A: PROFILES TABLE A-ll NIH Consensus Development Conferences, 1977-1986 389 Date Conference Title Cosponsora 1977 Sep. 14-16 Breast Cancer Screening NCI 1978 May 22 Educational Needs of Physicians and Public Regarding Asbestos Exposure NCI June 13-14 Dental Implants Benefit and Risk NIDR June 26-28 Mass Screening for Colo-Rectal Cancer NCI July 10-11 Treatable Brain Diseases in the Elderly NIA July 20 Indications for Tonsillectomy and Adenoidectomy: Phase I NINCDS Sep. 14 Availability of Insect Sting Kits to Non-Physicians NIAID Sep. 18-20 Mass Screening for Lung Cancer NCI Nov. 10-11 Supportive Therapy in Burn Care NIGMS Dec. 4-5 Surgical Treatment of Morbid Obesity NIADDK 1979 Feb. 15-16 Mar. 5-7 Apr. 23-24 Apr. 26-27 June 5 June 27-29 Sep. 10-11 Sep. 13-14 Oct. 15 Oct. 17-19 Pain, Discomfort, and Humanitarian Care Antenatal Diagnosis Transfusion Therapy in Pregnant Sickle Cell Disease Patients Improving Clinical and Consumer Blood Pressure Measuring Devices Primary Breast Cancer: Management of Local Diseases Steroid Receptors in Breast Cancer Intraocular Lens Implantation Estrogen Use and Postmenopausal Women Amantadine in the Prevention and Treatment of Influenza The Use of Microprocessor-Based "Intelligent" Machines in Patient Care Removal of Third Molars Nov. 28-30 1980 Apr. 10-12 Thrombolytic Therapy in Thrombosis May 19-20 Febrile Seizures July 14-16 Adjuvant Chemotherapy of Breast Cancer July 23-25 Cervical Cancer Screening: The Pap Smear Aug. 20-22 Endoscopy in Upper GI Bleeding Sep. 22-24 Childbirth by Cesarean Delivery Sep. 29-Oct. 1 CEA: Its Role as a Marker in the Management of Cancer Dec. 3-5 Coronary Bypass Surgery (HHS) NICHD NHLBI NHLBI NCI NCI NEI NIA NIAID DRS NIDR NHLBI NINCDS NCI NCI/NIA/NICHD NIADDK NICHD NCI NHLBI 1981 Mar. 2-4 Reye's Syndrome NINCDS/NIAID NICHD/NIEHS/DRS Nov. 4-6 CT Scan of the Brain NINCDS/NCI 1982 Jan. 13-15 Defined Diets and Childhood Hyperactivity NIADDK/NICHD Mar. 1-3 Total Hip Joint Replacement NIADDK Nov. 1-3 Clinical Applications of Biomaterials DRS 1983 Mar. 7-9 Critical Care Medicine NIH Clinical Center June 20-23 Liver Transplantation NIADDK Sep. 27-29 Treatment of Hypertriglyceridemias NHLBI Oct. 24-26 Precursors to Malignant Melanoma NCI

390 TABLE A-11 Continued ASSESSING MEDICAL TECHNOLOGY Nov. 15-17 Drugs and Insomnia: The Use of Medications to Promote Sleep (NIMH) Dec. 5-7 Dental Sealants in the Prevention of Tooth Decay NIDR 1984 Feb. 6-8 Diagnostic Ultrasound Imagingin Pregnancy NICHD/(FDA) Feb. 27-29 Analgesic-Associated Kidney Disease NIADDK Apr. 2-4 Treatment and Prevention of Osteoporosis NIADDK Apr. 24-26 Drug Therapy for Depression (NIMH) Sep. 24-26 Fresh Frozen Plasma: Indications and Risks NHLBI/(FDA) Dec. 3-5 Limb-Sparing Treatment: Adult Soft-Tissue and Osteogenic Sarcomas NCI Dec. 10-12 Lowering Blood Cholesterol to Prevent Heart Disease NHLBI 1985 Jan. 28-30 Travelers' Diarrhea NIAID Feb. 11-13 Health Implications of Obesity NIADDK/NHLBI Apr. 22-25 Anesthesia and Sedation in the Dentist's Office NIDR June 10-12 Electroconvulsive Therapy (NIMH) Sep. 9-11 Adjuvant Chemotherapy for Breast Cancer NCI 1986 Feb.b Smokeless Tobacco NCI/NIDR Apr. 21-23 Neurological Applications of Positron Emission Tomography (PET) NIH Clinical Center/ NINCDS/NIA/(NIMH) Apr.b Role of Nursing in the Management of Chronic Pain NIH Clinical Center Apr.b Health Maintenance Needs of the Elderly NIA Julyb Impact of HTLV-III Antibody Screening on Blood Banks NHLBI Aug.b Preventing the Spread of Infectious Disease in Dental Practice NIDR Sep.b Infantile Apnea and Home Monitoring NICHD Sep.b Magnetic Resonance Imaging NIH Clinical Center b The Utility of Plasmapheresis in Neurological Disorder NINCDS aEach conference is normally sponsored by OMAR and one or more Bureau, Institute, or Division of NIH: NCI: National Cancer Institute NHLBI: National Heart, Lung and Blood Institute NLM: National Library of Medicine NIADDK: National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases NIAID: National Institute of Allergy and Infectious Diseases NICHD: National Institute of Child Health and Human Development NIDR: National Institute of Dental Research NIEHS: National Institute of Environmental Health Sciences NIGMS: National Institute of General Medical Sciences NINCDS: National Institute of Neurological and Communicative Disorders and Stroke NEI: National Eye Institute NIA: National Institute on Aging DRS: Division of Research Services Sponsors from organizations outside NIH are shown in parentheses: HHS: Department of Health and Human Services NIMH: National Institute of Mental Health FDA: Food and Drug Administration bDate not set as of July 1985. SOURCE: OMAR.

APPENDIX A: PROFILES TABLE A-12 Examples of NIH Consensus Conference Questions Total Hip Joint Replacement, March 1-3, 1982. What are the indications and contraindications for total hip joint replacement? What are the current scientific principles guiding selection of materials,devices, and procedures for total hip joint replacement? What is the short-term and long-term prognosis for medical status and functional activity after total hip joint replacement? What are the medical and surgical complications of total hip joint replacement? What are the problems related to revision surgery for total hip joint replacement? In what directions should the science base and techniques of total hip joint replacement be advanced? Lowering Blood Cholesterol to Prevent Heart Disease, December 10-12, 1984. Is the relationship between blood cholesterol levels and coronary heart disease causal? Will reduction of cholesterol levels prevent coronary heart disease? Under what circumstances and at what level of blood cholesterol should dietary or drug treatment be started? Should an attempt be made to reduce the blood cholesterol levels of the general population? What are the directions for future research? Health Implications of Obesity, February 11-13, 1985 What is obesity? What is the evidence that obesity has adverse effects on health? What is the evidence that obesity affects longevity? What are the appropriate uses and limitations of existing height-weight tables? For what medical conditions can weight reduction be recommended? What should be the future directions of future research in this area? that would be clarified by the consensus ap- proach or a gap between current knowledge and practice that a conference might help to narrow. 3. The topic must have an adequately de- fined and available base of scientific infor- mation to answer the previously posed ques- tions. 4. The topic should be amenable to clarifi- 391 cation on technical grounds and the outcome should not depend mainly on the impressions or value judgments of panelists. 5. The timing of the conference should be such that it is likely to have a meaningful im- pact; i.e., it should neither be so early in the developmental course of a new technology that data are insufficient nor so late that the conference merely reiterates a consensus al- ready arrived at by the profession. The following additional elements are desir- able for positive consideration of a consensus topic: 1. Public health importance. The topic should affect a significant number of people. 2. Health care cost impact. The topic may have implications for reimbursement by agencies such as the Health Care Financing Administration. 3. Preventive impact. 4. Public interest. Before a conference topic is finally selected, it is agreed to by the directors of the BID and OMAR, and approved by the director of NIH. Forthcoming or pending conferences are discussed by the NIH Coordinating Com- mittee on Assessment and Transfer of Tech- nology to elicit suggestions and interest from other BIDs. Process Once a conference topic has been selected, a planning committee composed of OMAR, BID staff, the conference chairperson, and outside experts is formed to delineate key conference issues and specific questions relat- ing to the technology being assessed. These questions identify the most important issues concerning safety and efficacy and define the dimensions of the conference. The questions have normally been confined to those issues on which there is enough factual evidence to serve as a basis for consensus. The planning committees also recommend panelists, pro- gram format, and speakers. Background re- ports may also be prepared, and individual experts may be commissioned to compile summaries of the state of the science. The consensus process is designed to produce a

392 published document, called a consensus statement, which will be useful to clinicians, researchers, and the public. Consensus conferences are open meetings to which members of the public and the med- ical community are invited, and usually last 2~/: days. The first 1~/~ days are normally de- voted to a plenary session in which experts or representatives of task forces present infor- mation on the state of the science and the safety and efficacy of the technology. These presentations are followed by an open discus- sion involving speakers, panelists, and ques- tions from the audience. Following the plenary session, the panel convenes to draft consensus answers to the predetermined questions, considering the ex- pert opinions of the conference speakers and other views expressed at the meeting. The consensus view of the panel is not necessarily that of all panelists. If a panel cannot achieve full agreement on a particular point, the con- sensus statement may identify opposing or al- ternative opinions and/or majority-minority viewpoints. This document is read to the audience on the morning of the third day for further com- ment and discussion among the panel and au- dience. The panel may choose to incorporate comments received during this session for in- clusion in the final consensus statement. The conference concludes with a press confer- ence. Assessors Conference program planning committees cooperate with the BID and OMAR in choos- ing panelists. Chairpersons are selected for their stature as distinguished physicians and scientists and for their personal skills in chair- ing the open symposium portion of the con- ference and in leading the consensus panel. Chairpersons usually participate on the plan- ning committee and participate in framing the questions and selection of panelists and speakers. The size of panels has varied from 8 to 16 members; most have had 10 to 12 mem- bers. OMAR seeks balanced representation from various sectors from professional and community life, including at least two indi- ASSESSING MEDICAL TECHNOLOGY viduals from each of the following four cate- gor~es: 1. Research investigators in the field, i.e., academic clinicians and scientists who are ac- tive in the area of consideration but who are not professionally identified with advocacy or promotional positions with respect to the consensus topic. 2. Health professionals who are users of the technology, including practicing inter- nists, surgeons, pediatricians, family practi- tioners, nurses, and other members of the health care team. 3. Methodologists or evaluators such as epidemiologists and biostatisticians. 4. Public representatives such as ethicists, lawyers, theologians, economists, public in- terest group representatives, and patients. Although both adversary panels com- posed of persons having espoused opposing viewpoints and neutral panels- composed of persons not having publicly established po- sitions were used early on, the program now seeks neutral panels. Each CDP confer- ence involves participation of approximately three staff members from the NIH institute concerned, three staff members from OMAR, and logistical support provided by an outside contractor. Turnaround The current NIH pattern is to devote about 1 year to conference preparation and another 3 to 6 months to dissemination of conference results. A final consensus statement is nor- mally submitted for publication approxi- mately 1 to 3 weeks following the conference. Reporting By the end of 1985, the COP will have con- ducted more than 50 conferences. Table A-11 lists the conferences held since the time of the program's inception in late 1977. At the conclusion of each conference, the panel presents its findings to the news media in a public briefing. After a final consensus statement is approved by the panel, the docu- ment is published by OMAR and widely dis- seminated to health care providers and ad-

APPENDIX A: PROFILES ministrators, the biomedical research and education community, and the public. Con- ference reports and summaries are published in medical and science journals pertaining to the conference topic. Most consensus state- ments are published in the Journal of the American Medical Association (lAMA). Within 3 months after each conference, printed copies of consensus statements are mailed to over 20,000 individuals and organi- zations with interests relevant to the particu- lar conference topic. Copies of the consensus statement are also available from OMAR on request. Copies of background papers and task force reports may also be made avail- able, and the sponsoring bureaus may dis- tribute more detailed reports of the proceed- ings. An example of pre- and postconference reporting activity is shown in Table A-13. Impact The CDP is one of few medical technology assessment programs which has undergone TABLE A-13 Information Dissemination Activities for November 1981 NIH Consensus Conference on Computed Tomographic Scanning of the Brain Preconference Journals receiving announcements Flyers mailed Special invitation letters to professional society presidents Media press releases Telephone calls to local media Miscellaneous announcements (including Federal Register, NIH publications, posters, etc.) Ads in JAMA and NEJMa 112 4,750 36 125 60 Yes Yes Postconference Consensus statements mailed 19,000 Full statement published in JAMA Yes Journals receiving availability announcements 43 Statements mailed in response to personal requests 1,100 aJAMA, Journal of the American Medical Association; NEJM, New England Journal of Medicine. SOURCE: Jacoby, 1983. 393 formal evaluation. In addition to formal evaluation, the CDP has been subject to con- siderable discussion in various publications (e. g., Perry and Kalberer, 1980; Rennie, 1981; Blue Sheet, 1983; Kolata, 1983, 1985) and government reports (e.g., OTA, 1982~. Through experience and in response to program evaluations, the CDP has under- gone various modifications. The procedures for conference planning, formulation of questions, and report dissemination have be- come more standardized, as have the formats for conducting the conferences and the final consensus statements. Greater attention is given to including on the panels the various types of expertise needed for technology as- sessment. One indication of the program's impact is that it has served as a model for similar efforts in Britain, Sweden, Denmark, and The Netherlands (see, e.g., Smith, 1984~. NIH and Swedish representatives agreed to con- duct in 1982 consensus development confer- ences following similar formats on hip joint replacement. The Swedish conference was the first such conference held outside the United States (Rogers et al., 1982~. Britain's first consensus development conference, on coronary artery bypass grafting, was held in November 1984 (British Medical Journal, 1984~. Certain consensus statements have fallen short of addressing directly certain promi- nent issues. Consistent with CDP policy, con- ferences usually examine only the safety and efficacy of medical technology, and confer- ence questions are limited to issues for which sufficient data exist for reaching scientifically valid findings. Because the conferences do not address such matters as cost and avail- ability of other resources, some consensus statements may be of limited use in setting guidelines for clinical use of medical technol- ogy, e.g., frequency of Pap smears or the use of mammography. In the consensus state- ment issued on the diagnosis and treatment of Reye's Syndrome, none of the 15 conference questions was addressed to the controversial role of salicylates (aspirin), although limita- tions of studies indicating its association with Reye's Syndrome were cited (OTA, 1982~. Although the panel on liver transplantation

394 concluded that the procedure has merit, es- pecially because many transplant patients would otherwise die, the panel did not ad- dress the prominent issues of payment for liver transplants or the number needed should the procedure become generally avail- able (Kolata, 1983~. The conference on liver transplantation was held despite the preferences of OMAR to avoid conference topics for which limited data are available. Panel members noted the lack of data regarding frequency of liver dis- ease and success of liver transplants (Kolata, 1983). Because published final consensus state- ments generally do not reflect the debate which is likely to have been present among panel members, expert speakers, and audi- ences, concern has been raised that consensus statements are prone to consist of generalities representing the lowest common denomina- tor of discussion, i.e. the only points on which panel members can fully agree. An Of- fice of Technology Assessment report (1982) noted that the CDP conference format is not designed to limit problems associated with face-to-face interaction (e.g., relative domi- nance of viewpoints due to social or hierar- chical factors) in group settings, as are Delphi, nominal group, and other group pro- cesses. Rennie (1981) has suggested that con- sensus statements make fuller recommenda- tions about further research, and that panels be kept intact to obtain their opinion on funding research projects in their areas. Group judgment efforts such as the NIH program often seek to bridge gaps in and oth- erwise make sense of available research, to provide guidance for clinical practice. In so doing, expert panels may render recommen- dations relying to some extent on suggestive but not rigorously founded clinical evidence, e.g., derived from weaker epidemiological studies as opposed to randomized clinical trials. One recommendation of the NIH con- sensus panel on lowering blood cholesterol— to lower dietary cholesterol for all Americans age two onward may have been such an in- stance. (See Kolata t1985], Lenfant et al. t1985], and Steinberg t1985] for discussion.) This is a methodological concern of any group judgment effort, and is best addressed ASSESSING MEDICAL TECHNOLOGY with documentation of group judgment methodology and the characteristics of the research considered and assumptions made by the panelists. A number of concerns about the CDP which were voiced at its inception have not materialized. The program has been success- ful in clarifying its role as one of provider of information, rather than as government regu- lator dictating methods of clinical practice. The issuance of consensus statements has not orecinitated a flurry of malpractice action based upon consensus panel findings. There is no evidence that the program has stifled inno- vation. Consensus statements now routinely identify areas in which further development is needed. For example, the statement on total hip joint replacement highlighted several ma- terials innovations and areas for further study of implant failure mechanisms, and the state- ment on clinical applications of biomaterials identified specific areas in great clinical need of new biomaterials. Below are overviews of several formal studies of the process and impact of the pro- gram. Consensus Development Process The Center for Research on Utilization of Scien- tific Knowledge (CRUSK), University of Michigan, conducted a detailed study (Wort- man and Vinokur, 1982) of the CDP process to develop suggestions for strengthening the activity. The study employed measures of consensus conference outcome (e.g., quality of consensus statements), process (e. g., estab- lishment and adherence to procedural ar- rangements that facilitate panels' delibera- tions), and technology (e.g., controversy) in examining eight conferences held between July 1980 and March 1982. Data for the study were collected through direct observa- tions of conferences, personal interviews, analysis of consensus statements, and ques- tionnaires. Although CRUSK found that the process "operates well in meeting its major objectives . . . and is evaluated quite posi- tively," it did cite certain problems in the conduct of several of the conferences which may "disrupt tthe process] and result in an unsatisfactory product." CRUSK made rec- ommendations regarding selection of panel-

APPENDIX A: PROFILES ists, speakers and questions, conference for- mat, and drafting of consensus statements. Many of the CRUSK recommendations have been adopted by the CDP. Impact of OMAR Information D?ssemina- tion OMAR conducted a survey to measure the effectiveness of NIH consensus confer- ence studies as evidenced by the extent to which physicians were aware of the confer- ences and the conclusions reached at each (Iacoby, 1983~. The survey probed whether physicians in related specialties knew (1) that the conference was to be held, (2) that it was held, and (3) if they knew of the principal findings. More than 2,700 randomly sampled physicians in selected specialties were inter- viewed in two separate two-part telephone surveys (pre- and postconference) to test their awareness of NIH consensus development ac- tivities, especially the scheduling and conclu- sions of two consensus conferences. The con- ferences involved were the computed tomography (CT) scan of the brain (Novem- ber 1981) and hip joint replacement (March 1982~. These surveys determined that awareness of the conference varied greatly among dif- ferent physician specialties. Among the 10 physician specialties targeted for special dis- semination efforts, between 3 and 37 percent of the specialists contacted had heard of ei- ther conference, and between 1 and 15 per- cent were aware of the conclusions of either conference. Across specialties, respondents' main sources of information were the Journal of the American Medical Association, other professional publications, and statements mailed by OMAR. The highest awareness of the CT scan conference was among neurolo- gists: 37 percent of the neurologists surveyed were aware that the conference took place, and 15 percent were aware of the conclu- sions. The highest awareness of the hip joint conference was among orthopedic surgeons: 21 percent were aware of the conference, and 10 percent were aware of the conclusions. The study concluded that there is much room for improvement in information dissemina- tion and that it would be fruitful to examine physicians' information-seeking habits, such as examining the role of opinion leaders, so as 395 to better design strategies that more effec- tively disseminate conference results. Impact of Conference on Burn Therapy An impact study of the November 1978 NIH Consensus Conference on Supportive Ther- apy in Burn Care was conducted by Burke et al. (1981) using a survey of the 25 burn cen- ters at 6 burn care demonstration project sites of the National Burn Demonstration Project. The survey found, among the 2S center di- rectors, an overall average of 95 percent awareness for the conference's recommenda- tions regarding 12 specific treatment ap- proaches. Although the use level at the time of the conference was already relatively high for many of the recommended approaches, the survey found that an average of 68 per- cent of facility directors who were not al- ready using specific recommended ap- proaches reported an actual or potential practice change based on information re- ceived from the conference proceedings. All responding facility directors thought that the conference was important to their clinical practice, and most of those who indicated that they conduct ongoing research consid- ered the conference important to their re- search. The study findings indicated that the pub- lication of the proceedings of the conference in a supplement to the November 1979 lour- nal of Trauma was a major factor contribut- ing to the observed impact of the conference. Program-Wide Impact The Rand Cor- poration is conducting a study, to be com- pleted by 1985, of how consensus conferences have affected the knowledge, attitudes, and practices of health care professionals. The study has the following four major compo- nents: 1. a content analysis of the published con- sensus statements to identify message charac- teristics that may affect outcomes; 2. analyses of the professional literature for selected conference topics, covering pe- riods both before and after publication of conference findings; 3. design and analysis of a study of changes in hospital-based procedures that

396 have been the subject of consensus conference recommendations; 4. design and analysis of a survey of physi- cians, which will cover their knowledge atti- tudes, and self-reported practices with re- spect to one or more relevant technologies, while also eliciting information about their background, type of practice, and usual in- formation sources. Reassessment As of 1985, no technology has been re- assessed in a consensus conference. However, the program is prepared to undertake the re- assessment of any technology in which such reassessment is merited by new develop- ments. Funding/Budget The 1985 OMAR budget is approximately $1.8 million. The average cost of a confer- ence is approximately $145,000, including contractor costs, NIH staff time, and printing and other information dissemination costs. Example On the following pages is the full text of the questions, answers, and conclusion of the CDP conference on Liver Transplantation, held June 20-23, 1983. Sources Blue Sheet. June 29, 1983. Liver transplantation: randomized clinical trials "Much in Doubt." British Medical Journal. 1984. Consensus Develop- ment Conference: Coronary Artery Bypass Grafting. 289: 1527-1529. Clark, S., Office of Medical Applications of Re- search, National Institutes of Health. 1985. Personal communication. Jacoby, I. 1983. Biomedical technology information dissemination and the NIH consensus development pro- cess. Knowledge: Creation, Diffusion, Utilization 5(2):245-261. Jacoby, I., Acting Director, Office of Medical Ap- plications of Research, National Institutes of Health. 1984. Personal communication. Kolata, G. 1985. Heart Panel's conclusions ques- tioned. Science 227:40-41. ASSESSING MEDICAL TECHNOLOGY Kolata, G. 1983. Liver transplants endorsed. Sci- ence 221:139. Lenfant, C., B. Rifkind, and I. Jacoby. 1985. Heart Panel's conclusions (letter). Science 227:582- 583. National Institutes of Health. 1977. The Responsi- bilities of NIH at the Health Research/Health Care Interface. Bethesda, Md. National Institutes of Health. 1980. Consensus De- velopment Conference Summaries: Volume 3. Wash- ington, D.C.: U.S. Government Printing Office. National Institute of General Medical Sciences, National Institutes of Health. 1981. An Impact Study of the 1978 Consensus Development Conference on Supportive Therapy in Burn Care. Bethesda, Md. National Institutes of Health Consensus Develop- ment Panel. 1978. Statement of recommendations on breast cancer screening. Clinical Research 26:118- 120. OMAR. Undated. Participants' Guide to Consen- sus Development Conferences. Bethesda, Md. OMAR. 1978. Criteria for Identification of Candi- date Technologies for Consensus Development. Be- thesda, Md. OMAR. 1983a. Technology Assessment and Tech- nology Transfer in DHHS: A Report Submitted to the Department of Commerce in Compliance with the Stevenson-Wydler Technology Innovation Act of 1980. Bethesda, Md. OMAR. 1983b. Liver Transplantation: National Institutes of Health Consensus Development Confer- ence Summary. Volume 4, Number 7. Bethesda, Md. OMAR. 1983c. Guidelines for the Selection and Management of Consensus Development Confer- ences. Bethesda, Md. Office of Technology Assessment, U.S. Congress. 1982. Strategies for Medical Technology Assessment. Washington, D.C.: U.S. Government Printing Of- ~. rice. Perry, S., and J. T. Kalberer, Jr. 1980. The NIH consensus-development program and the assessment of health-care technologies: The first two years. New England Journal of Medicine 303: 169-172. Rand Corporation. 1983. Submission to the Office of Management and Budget of Supporting Statement and Data Collection Instruments for Assessing the Ef- fectiveness of the NIH Consensus Development Pro- gram. Volume I: Supporting Statement. Bethesda, Md. Rennie, D. 1981. Consensus statements. New En- gland Journal of Medicine 34:665-666. Rogers, E. M., J. K. Larsen, and C. U. Lowe. 1982. The consensus development process for medical technologies: A cross-cultural comparison of Sweden and the United States. Journal of the American Medi- cal Association 248:1880-1882. Shires, G. T., and E. A. Black, eds. 1981. Second

APPENDIX A: PROFILES Conference on Supportive Therapy in Burn Care. Journal of Trauma 21:665-752 (supplement). Smith, T. 1984. Consensus on cabbage. British Medical Journal 289:1477-1478. Steinberg, D. 1985. Heart Panel's conclusions (let- ter). Science 227:582. Their, S. O. 1977. Breast-cancer screening: A view Liver Transplantation National Institutes of Health Consensus Development Conference Summary Volume 4 Number 7 397 from outside the controversy. New England Journal of Medicine 297:1063-1065. Wortman, P. M., and A. Vinokur. 1982. Evalua- tion of NIH Consensus Development Process. Phase I: Final Report. Ann Arbor, Mich.: Center for Research on Utilization of Scientific Knowledge, University of Michigan. Introduction Since performance of the first human ortho- topic liver transplantation in 1963, over 540 such operations have been carried out in four medical centers in the United States and Western Europe. Additional liver tranplanta- tion procedures have been performed in other parts of the world, and more recently in several other American medical centers. Although extremely demanding and expen- sive, the operation has been shown to be technically feasible, and interpretable results have been reported from all four primary transplant-centers. These clearly demonstrate that liver transplantation offers an alternative therapeutic approach which may prolong life in some patients suffering from severe liver disease that has progressed beyond the reach of currently available treatment and conse- quently carries a predictably poor prognosis. However, substantial questions remain regard- ing selection of patients who may benefit from liver transplantation; the stage of their liver disease at which transplantation should be performed; survival and clinical condition of patients beyond the initial year after transplantation; and overall long-range benefits and risks of transplantation in the management of specific liver diseases. In order to resolve some of these questions, the National Institutes of Health on June 20- 23, 1983, convened a Consensus Development Conference on Liver Transplantation. After 2 days of expert presentation of the available data, a Consensus Panel consisting of hepa- tologists, surgeons, internists, pediatricians, immunologists, biostatisticians, ethicists, and public representatives considered the offered evidence to arrive at answers to the following key questions: Are there groups of patients for whom transplantation of the liver should be considered appropriate therapy? 2. What is the outcome (current survival rates, complications) in different groups?

398 3. In a potential candidate for transplanta- tion, what are the principles guiding selection of the appropriate time for surgery? 4. What are the skills, resources, and in- stitutional support needed for liver transplantation? 5. What are the directions for future research? 1. Are there groups of patients for whom trans- plantation of the liver should be considered appropriate therapy? Liver transplantation is a promising alternative to current therapy in the management of the late phase of several forms of serious liver disease. Candidates include children and adults suffering from irreversible liver injury who have exhausted alternative medical and surgical treatments and are approaching the terminal phase of their illness. In many forms of liver disease the precise indications and timing of liver transplantation remain uncer- tain or controversial. . . ASSESSING MEDICaL TECHNOLOGY agent, and hepatitis B-induced disease in which viremia persists..ln the latter in- stance, rapid reappearance of infection with progressive liver failure has been reported following transplantation. Primary biliary cirrhosis is a slowly pro- gressive cholestatic liver disease. Re- sults of transplantation appear favora- ble for patients with end-stage liver injury. The procedure may improve the quality of life. Inborn errors of metabolism may cause end-stage liver damage or irreversible ex- trahepatic complications. Transplanta- tion may be appropriate for such pa- tients. Hepatic vein thrombosis (Budd-Chiari syndrome) often results in progressive liver failure, ascites, and death. Patients who have not responded to anticoagula- tion or appropriate surgery for portal decompression may be candidates for transplantation. Sclerosing cholangitis, a chronic non- suppurative inflammatory process of the bile ducts, may cause liver failure. Less favorable results following transplanta- tidn in this group may be due to prior multiple surgical procedures, a diseased extrahepatic bile duct, the presence of biliary infection, or other factors. Primary hepa tic malignancy confined to the liver but not amenable to resection may be an indication for transplantation. Results to date indicate a strong likeli- hood of recurrence of the malignancy. Nonetheless, the procedure may achieve significant palliation. Alcohol-related liver cirrhosis and alcoholic hepatitis are the most common forms of fatal liver disease in America. Patients who are judged likely to abstain from alcohol and who have established clinical indicators of fatal outcome may be candidates for transplantation. Only a small proportion of alcoholic patients . . . Prolongation of life of good quality for pa- · tients who would otherwise have died has been reported in the following conditions: Extrahepatic biliary atresia is the most common cause of bile duct obstruction in the young infant. Patients who fail to respond to hepatoportoenterostomy (Kasai procedure) often benefit from liver transplantation. Recent data suggest that as many as two-thirds of these pa- tients survive for 1 year or more after transplantation. Chronic active hepatitis is caused by viral infections or drug reactions, but many cases remain unexplained. Some patients with progressive liver failure are candidates for transplantation. Currently, exceptions seem to include drug-induced chronic active hepatitis, which usually responds to removal of the chemical

APPENDIX A: PROFILES with liver disease would be expected to meet these rigorous criteria. Although fulminant hepatic failure with massive hepatocellular necrosis induced by hepatitis viruses, hepatotoxins, or certain drugs may warrant liver transplantation, rapid progression of the disease and multi-organ system failure frequently preclude this option. 2. What is the outcome (current survival rates, complications) in different groups? The survival and complication rates of pa- tients who have undergone liver transplanta- tion are the major criteria for judging efficacy. Data are available from four locations (Pitts- burgh; Cambridge, England; Hanover, Ger- many; and Groningen, The Netherlands). The interpretation of the existing data on survival is extremely difficult because no control data are given for comparison, surgical techniques and drug therapies varied over time, and pa- tient selection criteria and management dif- fered across centers. While sufficient data for thorough assessment of liver transplantation are not available to date, today certain trends appear to emerge: · Patients currently being accepted for transplantation have a high probability of imminent death and a low quality of life in the absence of transplantation. · Patients undergoing transplantation have an operative mortality (within 1 month) of 20 to 40 percent. One-year survival among transplant recip- ients since 1980 is favorable when com- pared with their expected course in the absence of transplantation. Since 1980, 1-year survival appears im- proved over the earlier transplant experience. . 399 · Data are insufficient to evaluate survival rates beyond 1 year following transplan- tation with current technologies. · Short-term quality of life is probably enhanced in many transplant survivors. We lack systematically gathered informa- tion on quality of life among long-term survivors. Severe non-lethal complications of transplan- tation frequently occur and must be taken into account in judging efficacy of this procedure. Massive hemorrhage is the most serious intra- operative and early postoperative problem. Other postoperative complications include renal dysfunction, rejection, biliary tract com- plications, graft vascular obstruction, and in- fection. With accumulating expertise in medi- cal and surgical management and with new developments in technology (e.g., intraopera- tive veno-venous bypass and cyclosporine), these complications can be expected to diminish. 3. In a potential candidate for transplantation, what are the principles guiding selection of the appropriate time for surgery? Individual patients have survived for many years with good quality of life after transplantation. Selecting an appropriate stage for a given ill- ness for liver transplantation is a complex issue: transplantation just prior to death may significantly diminish the life-saving potential of the procedure since hepatic decompensa- tion in its latest stages poses a formidable surgical risk. Transplantation early in the course of hepatic decompensation may de- prive a patient of an additional period of use- ful life. An ideally timed liver transplantation pro- cedure would be in a late enough phase of disease to offer the patient all opportunity for spontaneous stabilization or recovery, but in an early enough phase to give the surgical procedure a fair chance of success. For most patients, these phases are difficult to define prospectively. While no single best time for

400 surgery can be specified, transplantation should be reserved for patients in any of the following phases of disease: · When death is imminent. When irreversible damage to the central nervous system is inevitable. When quality of life has deteriorated to unacceptable levels. The exact choice of the time for liver trans- plantation in an individual requires the judg- ment of a qualified medical team and a well- informed patient. The following are offered as guidelines for individual liver diseases. · Extrahepatic Biliary Atresia Biliary enteric anastomosis (hepatoporto- enterostomy of Kasai) performed in the first 2 months of life provides significant improve- ment for at least 5 years in one-third of the patients, although cirrhosis and disappear- ance of the intrahepatic bile ducts occur with increasing age. While success of this pro- cedure cannot be predicted for the individual patient, it should be used as initial therapy for extrahepatic biliary atresia. In the absence of severe hepatic decompensation in these children, liver transplantation should be delayed as long as possible to permit the child to achieve maximum growth. In children with successful hepatoportoenterostomy, liver transplantation should be deferred until pro- gressive cholestasis, hepatocellular decom- pensation, or severe portal hypertension supervene. Multiple attempts at hepatoportoenterostomy or surgical porto-systemic shunting render eventual transplant surgery technically more difficult and operationally more dangerous and therefore should be avoided in favor of liver transplantation. · Chronic Active Hepatitis The potential for spontaneous remission and the complex course of chronic active hepatitis make valid predictions of the subsequent ASSESSING MEDICAL TECHNOLOGY course difficult except in the latest stages of the disease. Using strict criteria, patients can be identified who have almost no chance of survival beyond 6 months. Such patients may be suitable candidates for transplantation. · Primary Biliary Cirrhosis The indolent course of primary biliary cirrhosis and the potential for spontaneous improve- ment even in patients with advanced disease make transplantation potentially suitable only in the final stages of liver failure or when the quality of life has deteriorated to an unaccept- able level. · Alpha-1-Antitrypsin Deficiency Of the some 20 phenotypes In this genetic disorder, only Pi Z is associated with signifi- cant hepatic disease in children. Of infants with this phenotype, neonatal cholestasis occurs in 5.5 percent. Jaundice usually is transient, clearing before 6 months of age although biochemical evidence of activity may persist. Liver transplantation is indicated in children with Pi Z phenotype only when cirrhosis has developed and when evidence of hepatic failure is present. Adults with alpha-1-antitrypsin deficiency may have liver disease associated with phenotype Pi Z. MZ, or SZ. If hepatic failure occurs, liver transplantation may be indicated. · Wilson's Disease Patients with Wilson's disease usually are responsive to chelation therapy with penicillamine. However, some patients pre- sent with fulminant hepatic failure and/or pro- gressive disease unresponsive to adequate chelation therapy. Liver transplantation may be indicated in these instances. · Crigler-Najjar Syndrome Of the two types of this genetic disorder associated with severe unconjugated hyper- bilirubinemia, patients with Type I invariably develop bilirubin encephalopathy usually before 15 months of age. Because of the inevitability of central nervous system damage

APPENDIX A: PROFILES and the limitations of phototherapy, liver transplantation is indicated in such patients at an early age. · Miscellaneous Metabolic Diseases A number of rare genetic diseases may in- volve the liver and cause cirrhosis and even- tual hepatic failure. Patients with tyrosinemia, Byler's disease, Wolman's disease, and glycogen storage diseases Types O and IV may be candidates for hepatic transplantation. Liver transplantation may also be indicated for patients with certain genetic diseases asso- ciated with severe neurological complications, such as hereditary deficiency of urea cycle enzymes and disorders of lactate/pyruvate or amino acid metabolism. · Hepatic Vein Thrombosis The course of hepatic vein thrombosis is variable, and therefore transplantation should be reserved for patients with severe hepatic decompensation. The possibility of later transplant surgery should not discourage the use of portal venous decompression when otherwise indicated. · Primary Sclerosing Cholangitis No clinical, biochemical, serologic, or histologic factors have proved to be of value in predicting outcome. When appropriate at- tempts at biliary tract diversion and dilatation have failed, and death from liver failure is im- minent, liver transplantation should be con- sidered. · Alcoholic Liver Disease At least 50 percent of the cases of cirrhosis in the United States are attributable to the abuse of alcohol, and alcohol abuse is the leading cause of hepatic morbidity and mortality. Alcoholic liver disease is most favorably af- fected by abstinence. The natural history of untreated alcoholic hepatitis and/or cirrhosis is extremely variable, and there are few 401 precise prognostic indicators in any but the terminal phase of the disease. Liver transplantation may be considered for the patients who develop evidence of pro- gressive liver failure despite medical treat- ment and abstinence from alcohol. What are the skills, resources, and institu. tional support needed for liver transplant tation? The requirements for conducting a liver transplantation program by a sponsoring in- stitution are formidable. Accordingly, any in- stitution embarking on this program must make a major commitment to its support. In addition to the full array of services required of a tertiary care facility and a program in graduate medical education, an active organ transplantation program should exist. Few hospitals are likely to meet these pre- requisites. Liver transplant recipients are seriously ill before surgery. The transplant effort is pro- digious, and the postoperative intensive care interval, averaging 2 weeks, is punctuated by complications and frequent need for reopera- tion. In this context, experts in hepatology, pedia- trics, infectious disease, nephrology with dia- lysis capability, pulmonary medicine with respiratory therapy support, pathology, im- munology, and anesthesiology are needed to complement a qualified transplantation team. Extensive blood bank support to provide the needed copious quantities of blood compo- nents is mandatory. Similarly, sophisticated microbiology, clinical chemistry, and radiology assistance are required. Emotional support for patient and family warrants psychiatric partici- pation. Availability of effective social services to assist patients and families is indispen- sable. The transplantation surgeon must be trained specifically for liver grafting and must assem-

402 ble and train a team to function whenever a donor organ is available. Institutional commit- ment to the program mandates that operating room, recovery room, laboratory, and blood bank support exist at all times. Allocation of intensive care and general surgical beds is im- portant. Recruitment of a cohort of specialized nurses and technicians to staff these areas is necessary. Access to tissue typing capability; ongoing research programs in liver disease, organ preservation, and transplantation immu- nology; and available hemoperfusion and microsurgical techniques are desirable at- tributes of a transplantation effort. Participation in a donor procurement program and network is essential, and an interdisci- plinary deliberative body should exist to deter- mine on an equitable basis the suitability of candidates for transplantation. Institutions conducting liver transplantation are obligated to prospectively collect and share data in a coordinated, systematic, and comprehensive manner in all patients selected as transplantation candidates, so that the role of liver transplantation in the management of patients with liver disease can be assessed properly. Additional informa- tion permitting cost-benefit analysis should be secured. Finally, the panel feels that adherence to these guidelines detailing the essentials to conduct a transplantation program offers the best assurance of high quality in performing this very difficult operation. 5. What are the directions for future research? The Consensus Panel identified several broad areas related to liver transplantation in which critically important information is either una- vailable or so incomplete as to defy mean- ingful interpretation. It is recommended that a registry or clearinghouse be established for collection and evaluation of all available data on liver transplantation. Such a center would ASSESSING MEDICAL TECHNOLOGY develop unified criteria for selection of pa- tients for transplantation and for reporting and evaluating all data related to the outcome of the operation and the patients' postoperative and long-term condition. As methods of im- munosuppression improve and the logistic obstacles are resolved, the feasibility and desirability of randomized clinical trials of liver transplantation should be explored for suitable subgroups of patients with specific liver diseases. High priority also should be given to research projects related to several aspects of the transplant procedure itself. Means should be developed to improve preservation of human liver ex viva and criteria should be established to evaluate its viability. Improved control of organ rejection requires urgent attention; this includes thorough evaluation of the benefits and risks of cyclosporine as an immunosup- pressive agent in liver transplantation. The design of the hemodynamic support system during transplantation needs evaluation and potential improvement. Research should be encouraged for developing better supportive measures for patients in liver failure, including maintenance of proper renal and cerebral function. In the bhoad areas of the cause, pathogenesis, and natural course of chronic liver disease, present knowledge is fragmentary and in- complete, and research in these areas should be fostered and supported by all available means. Particular attempts should be made to determine the possible role of liver transplan- tation in the management of hepatocellular carcinoma at a stage when metastatic spread appears remote. Similarly, approaches should be sought to limit infection of the trans- planted liver by hepatotropic viruses. Finally, liver transplantation should be explored as a modality of replacement therapy in genetically determined multi-organ enzyme deficiencies.

APPENDIX A: PROFILES Conclusion After extensive review and consideration of all available data, this panel concludes that liver transplantation is a therapeutic modality for end-stage liver disease that deserves broader application. However, in order for liver trans- plantation to gain its full therapeutic potential, the indications for and results of the proce- dure must be the object of comprehensive, coordinated, and ongoing evaluation in the years ahead. This can best be achieved by expansion of this technology to a limited number of centers where performance of liver transplantation can be carried out under op- timal conditions. Members of the Consensus Development Panel were: Rudi Schmid, M.D. (Panel ChairmanJ Professor of Medicine and Dean University of California, San Francisco School of Medicine San Francisco Medical Center San Francisco, California Donald M Berwick, M D Assistant Professor of Pediatrics Harvard Medical School Acting Director of Research Harvard Community Health Plan Boston, Massachusetts Burton Combes, M D Professor of Internal Medicine University of Texas Health Science Center at Dallas Dallas, Texas Ralph B. D'Agostino, Ph D Professor of Mathematics and Statistics Boston University Boston, Massachusetts Stuart H. Danovitch, M D Private Practice of Gastroenterology Washington, D C 403 Harold J. Fallon, M.D. Professor and Chairman Department of Medicine Medical College of Virginia Richmond, Virginia Olga Jonasson, M.D. Professor of Surgery University of Illinois Chief of Surgery Cook County Hospital Chicago, Illinois Charles E. Millard, M.D., A.B.F.P. Family Practitioner Medical Associates of Bristol County Vice Chairman Biomedical Ethics Commission Roman Catholic Diocese of Providence Bristol, Rhode Island Linda Miller, M.S. Executive Director Volunteer Trustees of Not for Profit Hospitals Washington, D.C. Frank G. Moody, M.D. Professor and Chairman Department of Surgery University of Texas Medical School at Houston Surgeon-in-Chief Hermann Hospital Houston, Texas William K. Schubert, M.D. Professor and Chairman Department of Pediatrics University of Cincinnati College of Medicine Physician Executive Director Children's Hospital Medical Center Cincinnati, Ohio Laurence Shandler, M.D. Private Practice of Pediatrics Santa Fe, New Mexico

404 Henry J. Winn, Ph.D. Senior Associate in Surgery Harvard Medical School Immunologist General Surgical Services Massachusetts General Hospital Boston, Massachusetts Members of the Planning Committee were: Steven Schenker, M.D. (ChairmanJ Professor of Medicine and Pharmacology Chief, Division of Gastroenterology and Nutrition Department of Medicine University of Texas Health Science Center San Antonio, Texas Itzhak Jacoby, Ph.D. Deputy Director Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland Sarah C. Kalser, Ph.D. Program Director for Liver and Biliary Diseases National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland Curtis Meinert, Ph.D. Professor of Epidemiology and Biostatistics School of Hygiene and Public Health Johns Hopkins University Baltimore, Maryland Harold P. Roth, M.D. Director Division of Digestive Diseases and Nutrition National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases National Institutes- of Health Bethesda, Maryland Paul S. Russell, M.D. John Homans Professor of Surgery Harvard Medical School Boston, Massachusetts ASSESSING MEDICAL TECHNOLOGY The conference was sponsored by: National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases Lester B. Salans, M.D. Director Office of Medical Applications of Research J. Richard Grout, M.D. Director

National Library of Medicine National Institutes of Health 8600 Rockville Pike Bethesda, MD 20209 (301) 496 4725 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ ' Effectiveness Cost-Benefit X X Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative Stage of Technologies Assessed X Emerging/new X Accepted use X Possibly obsolete, outmoded Application of Technologies X Prevention X Diagnosis/screening X Treatment X Rehabilitation Assessment Methods X Laboratory testing Clinical trials X Epidemiological and other observational methods X Cost analyses X Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $300,000* * This amount covers intramural technology assessment activities only. A sig- nificant but undocumented fraction of the $7.5 million spent extramurally in 1984, via the grants mechanism, includes functions that may be classified as tech- nology assessment. NATIONAL LIBRARY OF MEDICINE NATIONAL INSTITUTES OF HEALTH Introduction The National Library of Medicine (NLM) is the world's largest research library in a sin- gle scientific and professional field. The li- brary collects materials exhaustively in all major areas of health sciences and to a lesser degree in such areas as chemistry, physics, botany, and zoology. The collection stands at 405 3.3 million items, including books, journals, technical reports, manuscripts, microfilms, and pictorial materials. The library was es- tablished in 1836 as the Library of the Army Surgeon General's Office, and it remained in the military until 1956, when it was trans- ferred to the Public Health Service and up- graded to the National Library of Medicine. NLM serves as a national resource for all U.S. health science libraries. Lending and other services are provided through the Re-

406 gional Medical Library Network consisting of more than 2,000 basic unit libraries (mostly at hospitals), 125 resource libraries (at medi- cal schools), 7 regional medical libraries, and the NLM as a national resource for the entire network. The library also provides a variety of educational, audiovisual, and publication services, support for medical library develop- ment; training for health information spe- cialists; and technical consultation and re- ASSESSING MEDICAL TECHNOLOGY vision of Specialized Information Services, and the Lister Hill National Center for Biomedical Communications. The Extramu- ral Programs Division supports research at universities and not-for-profit organizations in the areas of generation, organization, and utilization of health information. The Lister Hill National Center for Biome- dical Communications is the research and de- velopment arm of NLM. The Center was es- search assistance. tablished in 1968 and reorganized in 1983 to NLM's computer-based Medical Litera- include the functions of NLM's National tore Analysis and Retrieval System Medical Audiovisual Center. Through the (MEDLARS) was established to achieve rapid bibliographic access to the library's store of biomedical information. The estab- lishment of this system was a pioneering ef- fort in the emerging computer technology of the early 1960s for the production of biblio- graphic publications and for conducting in- dividualized searches of the literature. The best known of the MEDLARS family of 20 databases is MEDLINE. Index Medicus is the monthly subject/author guide to arti- cles in nearly 3,000 journals prepared from MEDLINE. Other MEDLARS databases are TOXLINE (Toxicology Information Online), HEALTH PLANNING AND ADMIN, CAN- CERLIT, and BIOETHICSLINE. More than four million references to current and historical journal articles, books, and audio- visual materials are stored in MEDLARS da- tabases. Some MEDLARS databases are available through commercial database ven- dors such as DIALOG and BRS. Today, MEDLARS search services are available on- line to researchers at 2,500 MEDLARS cen- ters at biomedical libraries and other institu- tions in the United States and are available to individuals via personal computers and dial- in lines. In addition, there are 14 overseas na- tional or regional MEDLARS centers. The U. S. institutions performed 2.8 million searches in 1984. The design and initial im- plementation of MEDLARS III is being coor- dinated by the NLM Office of Computer and Communications Systems. The major components of NLM are the Of- fice of the Director, Office of Administra- tion, Office of Computer and Communica- tions Systems, Division of Library Opera- tions, Division of Extramural Programs, Di- Lister Hill Center, NLM conducts and sup- ports research in techniques and methods for recording, storing, retrieving, and communi- cating health information. The Lister Hill Center has six branches: Communications Engineering, Computer Science, Informa- tion Technology, Audiovisual Program De- velopment, Health Professions Applications, and Training and Consultation. Other Lister Hill Center resources are the new National Learning Center for Educational Technol- ogy, which provides an environment for demonstrating new technologies in com- puter-based education for the health sci- ences. Purpose The purpose of NLM assessment activities is to evaluate new and existing biomedical in- formation technologies for the enhancement of information dissemination and utilization among health professionals and other users. It is intended that assessments be carried out as an integral part of the research and devel- opment process, and of efforts to improve on- going operations of the library. The NLM Board of Regents intends that the American public receive rapid and easy access to biomedical information disseminated by NLM and other sources. To this end, NLM seeks to work cooperatively with database producers and vendors in the private sector to create linkages, reduce production costs, and to otherwise facilitate access to all relevant health information.

APPENDIX A: PROFILES Subjects of Assessment NLM assesses a major subgroup of support systems related to biomedical information in- cluding but not limited to systems for infor- mation storage, retrieval, and dissemination; teaching/learning systems, and artificial in- telligence or expert systems. A number of new and emerging technologies that are be- ing applied in other fields are also being as- sessed by NLM for use in biomedical infor- mation systems. Examples are laser discs, microprocessors, microcomputers, micro- wave and cable television, satellite comrr~u- nication systems, computer-assisted instruc- tion, and speech recognition systems. Table 407 A-8 briefly describes intramural NLM proj- ects in related areas. The Lister Hill Center is also investigating the potential of optical videodisc technology for document preservation, storage, and re- trieval, and has under way several projects that combine videodisc technology with mi- crocomputers to develop new health-science teaching materials. NLM has made a number of extramural grants and contracts for assessing the man- agement of health information. At Mount Si- nai School of Medicine in New York City, re- ports of controlled clinical trials are analyzed to determine how valid the trial procedures are. At Case Western Reserve University in TABLE A-8 Descriptions of Selected Research and Development Projects Coordinated by the Lister Hill Center, NLM · The Technological Innovations in Medical Edu- cation (TIME) Project involves several Lister Hill branches and addresses the potential application of the new technologies of microprocessor, interactive laser disc, and speech recognition to the education of medical practitioners and students. The project is ex- ploring educational capabilities by developing a series of problem-based, patient-related clinical simula- tions. · The Electronic Document Storage and Retrieval (EDSR) Program is an effort to design, develop, and evaluate a laboratory facility that will serve as an en- gineering prototype to electronically store, retrieve, and display documents acquired by the library. The development of this experimental system involves in- tegrating various components such as a document capture subsystem, high density storage media, docu- ment display subsystem, and system controller. The resulting engineering prototype enables both techni- cal and operational evaluation. The prototype will be used to evaluate and correct problems encountered in capturing images, transferring images on output de- vices, and evaluating factors such as display image quality, system reliability, maintainability, the man- machine interface, and the utility of such a system for NLM information processing needs. · The Automated Classification and Retrieval Pro- gram investigates, develops, and evaluates informa- tion science, computational linguistics, and artificial intelligence techniques supporting the automated classification and retrieval of biomedical literature. The program includes projects in the areas of natural language understanding, knowledge representation, and information retrieval. The goal of these projects is to explore their application to the development of au- tomated systems for identifying relevant concepts and main ideas from printed documents. · The Distributed Information System (DIS) Pro- gram encompasses several projects related to the effec- tive distribution of advanced information systems technology. The Interactive Information Manage- ment System (IIMS) project is designed to produce a working model for testing and demonstrating ad- vanced information management and retrieval tech- niques that can be applied to full-text databases. The Network Access Information Workstation Project is to develop a user-friendly microcomputer workstation that can facilitate access to different on-line informa- tion sources. The Information Retrieval Testbed Sys- tem, which evolved from earlier work in the area of natural-language queries and statistical retrieval tech- niques, is intended to create a system that will enable evaluation of the performance of statistically based in- formation retrieval systems. · The NLM Audiovisual Program Development Branch applies current and emerging video communi- cation technologies and audiovisual techniques to Lister Hill projects. Among its projects, videodisc slides of skin disorders are being tested in medical edu- cation settings to evaluate their utility as a teaching/ learning tool and as an aid in diagnostic decision mak- ing. Experiments are under way to ascertain if optical videodisc recording provides sufficient resolution for cataloging and analyzing brain sections, and to deter- mine whether photographic copies can be used in the videodisc production process, rather than actual brain sections.

408 Cleveland, the usage of medical libraries has been surveyed in a study that combines usage statistics with data on information service costs. In the area of medical informatics, Stan- ford University research in computerized representation of medical knowledge has yielded a computer program that represents and assesses treatment planning for cancer patients. At Latter Day Saints Hospital in Salt Lake City, computer-based logic is being studied for diagnosis and treatment of coro- nary artery disease and other diseases. The vast amount of biomedical information now available and the increasing sophistication of computer and communications technology have prompted the use of artificial intelli- gence techniques in the development of ex- pert systems, or systems that will aid clini- cians in making patient-related decisions. A full cycle of national field testing to validate the automated consultative systems has yet to be completed. NLM is committed to developing proto- types of the Integrated Academic Informa- tion Management System in the coming years. This far-reaching effort would inte- grate the myriad sources of health-related in- formation within the modern academic health center. The system would pull to- gether a variety of information sources pa- tient records, laboratory results, clinical de- cision-making systems, and the vast professional literature of biomedicine for instant access by health professionals, fac- ulty, and students. The lack of a standardized language con- tinues to be a fundamental impediment to the widespread adoption of computer-based information systems in medicine. NLM is embarking on a long-term coordinative effort to develop, implement, and evaluate a uni- fied medical language system that integrates terminology in biomedical research, patient care, and hospital management. The Lister Hill Center holds monthly semi- nars in which outside experts in areas of in- creasing interest to biomedical communica- tions researchers discuss their recent efforts. Among the 1984 topics were: · human factors design of computer dia- logues ASSESSING MEDICAL TECHNOLOGY · physician's judgments about estrogen re- placement therapy · a study of clinical decision making · feedback systems for improving clinical judgment · information compression techniques · artificial intelligence: problems in knowledge representation · optical disk technology and library in- formation · computer simulation of the patient-phy- sician encounter · designing interactive computer systems Stage of Diffusion NLM assesses biomedical information technologies that are new and emerging, in accepted use, and possibly obsolete or out- moded. Concerns NLM assessment activities are concerned with effectiveness (including technical per- formance), cost, and cost-effectiveness. Requests Requests for assessment may originate with intramural R&D staff, NLM manage- ment, and officials of NIH, DHHS, and Con- gress. Extramural requests follow the proce- dures governing the grants process; these are typically investigator-initiated projects sub- mitted by universities and not-for-profit or- ganizations. Selection Priorities for selecting candidate assess- ment projects are influenced by the source of the request, current and anticipated infor- mation needs of the biomedical community, potential impact on the performance of NLM's statutory mission, and availability of funds. Process NLM assessment processes vary according to subject. Assessments may involve field test-

APPENDIX A: PROFILES ing and evaluation, simulation, experiments with prototypes, cost analyses, consensus de- velopment, and literature syntheses. For in- stance, the NLM Hepatitis Knowledge Base Project (active from 1977 to 1983) was a com- puter-based synthesis of information on viral hepatitis formulated by consensus of geo- graphically dispersed experts who were linked to each other and to project staff via a computer conferencing network. A full-scale field test and evaluation of the prototype Hepatitis Knowledge Base addressed its tech- nical performance, degree of user accep- tance, and cost-effectiveness in light of other sources of viral hepatitis information. Infor- mation in the Toxicology Data Bank is being similarly assessed using computer conferenc- ing technology. NLM is planning a consensus development conference for late 1986 on computer-based clinical consultation sys- tems, to be cosponsored by the NIH Office of Medical Applications of Research. The re- cent NLM assessment of on-line catalog sys- tems, as reported under Example below, in- volved testing of prototype systems and user surveys. The educational capabilities of the Technological Innovations in Medical Edu- cation (TIME) project are being tested using problem-based patient-related clinical simu- lations. Some technologies supported by the Extra- mural Programs Division have been assessed in clinical settings. These include the expert systems HELP, which has been installed at the Latter Day Saints Hospital in Salt Lake City, and CADUCEUS, which is undergoing testing at the University of Pittsburgh Medi- cal Center. Assessors Assessment activities are performed intra- murally by in-house R&D and operations staff and extramurally within the framework of NLM's grants process. Projects involving multiple library divisions are carried out by a specially constituted Operations Research Group (ORG) located in the NLM's Office of Planning and Evaluation. ORG also serves to coordinate all planned and ongoing evalua- tions within NLM. Whenever feasible, evalu- ations are designed to allow for the participa- 409 tion of the community ultimately affected by the product or service in question, including health professionals, researchers, educators, practitioners, and students. NLM has three public advisory groups that participate with staff in the assessment pro- cess. The Board of Regents of NLM advises the Office of the Director on all important matters of library policy, among which are final review of proposals for support of re- search in biomedical information systems and special scientific projects. The Biomedi- cal Library Review Committee advises NLM and reviews applications and makes recom- mendations to the Board of Regents regard- ing research and other proposals submitted to NLM. The Board of Scientific Counselors re- views the library's intramural research and development programs. Ad hoc advisory or oversight committees, which may include non-NLM staff such as library professionals, computer scientists, and other researchers, are often an important adjunct to NLM- sponsored evaluations. Turnaround Assessments are generally carried out within a period of 6-18 months. Evaluations lasting up to 3 years may be appropriate in certain instances wherein the study design in- corporates both formative and summarative features. Reporting Reports of NLM technical assessment ac- tivities are routinely transmitted to the source of the request. Study reports may also be filed with National Technical Information Service (NTIS), Educational Resources Information Center (ERIC), and similar document distri- bution centers. NLM staff are also encour- aged to report study findings at professional meetings and conferences, and in the open scientific and technical literature. Impact Evaluation studies performed by NLM have affected R&D activities as well as the scope and availability of the library's prod-

410 ucts and services. Examples are the follow- ~ng. · The field test and evaluation of the Hep- atitis Knowledge Base system demonstrated the utility and cost-effectiveness of computer conferencing technology as a means for vali- dating and updating the contents of a data- base by expert consensus. The technology has since been adopted as an important feature of other fact-based information systems devel- oped and operated by NLM. · A survey of users of NLM's Videocassette Loan Program resulted in a management de- cision to expand the program to videocas- settes in NLM's collection, thereby partially achieving the goal of providing access to ma- terials in this medium comparable to the ac- cess for print media. · A study of NLM's coverage of the medi- cal behavioral services compared the perfor- mance of MEDLARS with that of alternative health-related databases. The finding served to document the impact of the library's present coverage and indexing policies, and has led to a reconsideration of these policies and the use of the research technologies with other subject literatures. Reassessment Products and services for the nation's biomedical community are reassessed as part of the R&D process, and technologies in- volved in NLM's own internal operations are evaluated and improved periodically. Reas- sessment is especially important given the rapidly evolving nature of computer technol- ogy and other innovations applicable to biomedical information systems. The MEDLARS system, which governs both in- house technical processing and the on-line availability of the derivative bibliographic databases is now undergoing its torch major reassessment and updating. The controlled indexing vocabulary, MeSH, is itself continu- ously reassessed as is the list of journals se- lected for inclusion in Index Medicus and MEDLINE. Funding t Budget The BY 1984 budget for NLM was approx- imately $50.2 million. Although NLM's ASSESSING MEDICAL TECHNOLOGY budget has increased in most years since 1972, in constant dollars its budget has dropped 22 percent since 1974. The R&D budget for FY 1984 was approximately $14.1 million, including $8.2 million for the Lister Hill National Center for Biomedical Com- munication. In FY 1984, NLM obligated $7.5 million for grants and made 103 new and renewal grant awards. These included grants for library resources and publications, as well as research in biomedical communi- cations. There are no budget line items for technol- ogy assessment as such; however, it is esti- mated that NLM devoted $0.3 million to in- tramural technology assessment activities in FY 1984. A significant but unknown amount of the $7.5 million FY 1984 extramural grant program was devoted to technology assess- ment. Of course, the bulk of the library's op- erating budget can be said to be devoted to biomedical information transfer. Example On the following pages is a report of an NLM intramural assessment of two proto- type public-access on-line catalog systems de- signed to replace conventional card catalogs. This report was published in Information Technology and Libraries in 1984 and is re- produced here with permission. Sources Bernstein, L. M., E. R. Siegel, and C. M. Gold- stein. 1980. The hepatitis knowledge base: A proto- type information transfer system. Annals of Internal Medicine 93:169-181. National Institutes of Health. 1983. National Insti- tutes of Health Organization Handbook. Bethesda, Md. , . ~ ~ . National Institutes of Health. 1983. NIH Public Advisory Groups: Authority, Structure, Functions, Members. Bethesda, Md. National Institutes of Health. 1984. NIH Data Book. Bethesda, Md. National Library of Medicine. 1985. National Li- brary of Medicine Programs and Services Fiscal Year 1984. Bethesda, Md. National Library of Medicine. 1985. Fact Sheet. Bethesda, McI. Office of Medical Applications of Research, Na- tional Institutes of Health. 1984. Technology Assess-

APPENDIX A: PROFILES ment and Technology Transfer in DHHS: A Report Submitted to the Department of Commerce in Com- pliance with the Stevenson-Wydler Technology Inno- vation Act of 1980 (P.L. 96-480~. Bethesda, Md. Siegel, E. R., Special Assistant for Operations Re- search, National Library of Medicine. 1985. Personal communication. 411 Siegel, E. R., K. Kameen, S. K. Sinn, and F. O. Weise. 1984. A comparative technical performance and user acceptance of two prototype online catalog systems. Information Technology and Libraries 3~1~:35-46. Smith, K. A., Deputy Director, National Library of Medicine. 1985. Personal communication.

412 ASSESSING MEDICAL TECHNOLOGY A Comparative Evaluation of the Technical Performance and User Acceptance of Two Prototype Online Catalog Systems* Elliot R. Siegel, Karen Kameen, Sally K. Sinn, and Frieda 0. Weise The National Library of Medicine (NLMJ conducted a comparative evalua- tion of two prototype patron accessible online catalog systems within the same operational environment. The study design provided for the assessment of both systems on the basis of technical performance and user acceptance by NLM's patrons and staff. This article describes the study's research strategy and methods, some aspects of which are unique to the evaluation of online information systems. Included is a description of verification and limits test- ing that were used to determine and document the extent to which both sys- tems met the technical performance requirements specified a priori for an NLM-based online catalog. User acceptance was addressed in three ways, each com Elementary in sco pe and methodology: a Sam pie Search Experiment designed to provide control over potentially confounding variables; a Com- par~son Search Experiment intended to maximize the authenticity of study conditions; and a User Survey characterizing users'catalog information needs and searching behavior. The results of technical performance testing were separately corroborated by a strong and consistent pattern of findings from the three studies of user acceptance. Overall, users of the online catalog at NLM are relatively infrequent library visitors and represent a broad cross sec- tion of professional roles and occupations. Most users of the online catalog come with subject-related information, are looking for books on a subject, and search by subject. The decision to adopt one of the two prototypes tested was largely based on that system's relatively superior performance in conduct- ing subject-related searches that, as has also been reported recently in other studies of online public access catalogs, Is the most important determinant of user satisfaction and acceptance of this new technology. *Portions of this paper were presented at the Fourth >national Online Meeting, O'er York, New York, April 12-14, 1983: and the Eight`- third Annual Meeting of the Medical Library As- sociation, Houston, Texas, Mas 27-June 2, 1983. BACKGROUND Movement toward the design and devel- opment of patron accessible online infor- mation systems is receiving substantial im- Elliot R. Siegel is special assistant for Operations Research, Office of the Director; Karen Kameen is librarian, Bibliographic Services Division; and Sally K. Sinn is assistant head, Catalog Section, Tech- nical Services Division; all at the National Library of Medicine, Bethesda, Maryland. Frieda O. Weise was formerly assistant head, Reference Section, Reference Services Division at NLM and is now assis- tant director for Public Services, Health Sciences Library, University of Maryland, Baltimore. No copyright is claimed on this article, which the authors wrote as part of their official duties as employees of the U.S. government.

APPENDIX A: PROFILES petus from the nation's library community. An important aspect of this trend is the in- creasing availability of computer-based public access catalog systems, developed ei- ther as part of an integrated effort at library automation or as a separate patron service. The economic incentive is frequently sig- nificant given the increasingly prohibitive costs of maintaining, updating, and revis- ing the conventional card catalog. To the credit of the library community, the proliferation of "homegrown" and commercially available public access cata- log systems has also seen the advent of sev- eral noteworthy attempts at conducting formalized assessments of these systems. See, for example, the Council on Library Resources' nationwide survey of user re- sponses to public online catalogs, Hildreth's detailed analysis of user inter- face features,2 and Markey's study using the focus group interview technique with li- brary patrons and staff.3 However, as with other studies of online information systems, these frequently suffer from a methodolog- ical weakness in which the confounding in- fluence of a "novelty effect" can make even a relatively poor system appear better than whatever it is replacing. This is especially true for single system studies, but it also ap- plies to studies purporting to assess multiple systems, but which for a variety of politi- cal, logistical, or economic reasons are un- able to examine the technical performance and/or user acceptance of more than one system within a single operational environ- ment. Recently, the National Library of Medi- cine (NLM) was fortunate to be in a posi- tion in which it was feasible to mount a comparative evaluation of two prototype patron accessible online catalog systems within the same operational environment. This study was intended to provide an ob- jective, comparative assessment of the can- didate systems, using the same physical space, library staff, computer terminals, database, and user populations. This paper describes the study's research strategy and methodology, some aspects of which are unique to the evaluation of online informa- tion systems. The major study findings that led to the adoption of one of the two proto- type online catalogs are summarized. 413 APPROACH Initial study plans specified that the study would be performed in-house over the course of nine months. While this placed a heavy burden on already busy li- brary staff, we were in a position to draw upon the unique technical skills and capaci- ties of persons from nearly all divisions of the library who were familiar with one an- other and their respective job functions. The learning curve for those involved was probably shorter than if the study had been delegated to an outside group. In January 1982, the study group under- took as its first task the specification of re- quirements and capabilities of an NLM- based online catalog system intended for use by NLM patrons and nontechnical staff. Existing publications and NLM staff members were consulted. What resulted was a detailed list of specifications that ad- dressed the key areas of database content, composition of records, search/access fea- tures, user cordiality, and display features. Each area was further categorized as to whether a feature or attribute was to be "required" for the prototype test version; "necessary" for a fully implemented sys- tem, but not required for the initial test ver- sion; or "optional," its need not yet having been determined for an NLM-based sys- tem. These specifications were organized as a "technical requirements" or criteria doc- ument, against which the candidate online catalog systems would be evaluated.4 Two experimental in-house systems were selected for test and evaluation based upon their potential for meeting the technical re- quirements as specified. They are CITE (Current Information Transfer in English), incorporating a user-friendly front end to the CATLINE * system operating on the li- brary's IBM 3033 multiprocessor; and the public access catalog module of the ILS (In- tegrated Library System), which, for this study, uses the current contents of the *Designed for staff access, CATLIKE its used by the library s reference and technical staff for in- formation retries al and file maintenance. At the time of the stud`, the database contained some 225,000 current and an additional 245~000 retro- spective machine-readable records for the li- brars s collection of printed materials.

414 ASSESSING MEDICAL TECHNOLOGY CATLINE database and operates on a ded- icated l~ata General S230 minicomputer. CITE and ILS are going research-and- development efforts in NLM's Specialized Information Services division and the Lister Hill National Center for Biomedical Communications, respectively.5 In March, the designers of both systems were re- quested further to develop and equip their prototypes to conform to the technical re- quirements for an NLM-based online cata- log. In the case of CITE hereafter re- ferred to as System A this involved continuing with the production and refine- ment of new software. For ILS hereafter referred to as System B—the principal hur- dle was to create a functionally acceptable database suitable for operational use by li- brary patrons during the test period. This involved the conversion of nearly one- quarter of a million current (post-1966) CATLINE records to MARC format, and their loading and indexing on the host mini- computer. The time allotted for these activ- ities was very short given the planned dura- tion of the study. System A was successfully established and made ready for testing in April, and System B in June. Concurrently with the above, another working group proceeded with the devel- opment of context-specific online HELP fa- cilities for both systems, printed instruction materials, signs informing patrons of the impending experiment, and modification of terminals to highlight certain function keys (e.g., RETURN), and disable others (e.g., BREAK). A battery of six Hewlett- Packard 2626A CRT terminals, with inter- nal printers, was assembled immediately adjacent to the main entrance of the public catalog area. A separate working group fo- cused on refinement of the preliminary study design and construction of the several data collection instruments that would be used during the various phases of the study. The study design provides for the inde- pendent and comparative assessment of System A and System B as to both technical performance and user acceptance (i.e., ef- fectiveness from the users' standpoint). The assessment of technical performance deals primarily with the systematic determina- tion and documentation of the extent to which the candidate systems meet the tech- nical specifications for an NLM-based on- line catalog system, as defined by the study group in its"requirements" document. This approach has the virtue of making known to the systems designers, in ad- vance, the criteria against which their sys- tems would be evaluated; ensuring that both systems would be evaluated against the same performance criteria; and ensur- ing that if shortcomings were discovered, documentation would be sufficient to iden- tify clearly the weakness or malfunction and, whenever possible, suggest a strategy for improvement. In addition, "stress" or "limits" testing would seek to elicit addi- tional data on the outer ranges of system search capabilities, should the above meth- ods prove insufficiently sensitive to discrim- inate between the two systems. The concept of "user acceptance," while more difficult to operationally define and measure, is addressed in three ways—each complementary in scope and methodology: (1) a questionnaire User Survey character- izing the nature of users' catalog searching requirements, relevant demographic fac- tors, and satisfaction with search outcomes on Systems A and B. judged separately and independently; (2) a partially controlled but authentic Comparison Search Experi- ment in which members of a smaller sam- ple of library patrons conduct a search of their own choosing sequentially on both Systems A and B and briefly record comparative system preferences in several key areas relating to search outcome; and (3) a controlled field experiment, the Sam- ple Search Experiment, utilizing a panel of NLM staff conducting equivalent but different searches on both systems, simu- lating representative uses of an online cata- log. The Sample Search Experiment con- trols for important variables that the Comparison Search Experiment does not; namely, the searcher's professional role/oc- cupation, type of search performed, data- base size, and a potentially confounding "transfer effect" stemming from the con- duct of identical searches on both systems. The research strategy underlying this ap- proach to user acceptance seeks to produce a comprehensive data set pertaining to on- line catalog use at the NLM; distribute equitably and realistically the response

APPENDIX A: PROFILES Table 1. User Acceptance of System A and System B.: Key Variables Measured in the Three Study Methods Study Variables Dependent Variables Amount of information retrieved Proportion of retrieved items judged relevant Number of known relevant items retrieved Time to complete search Ease of system use Satisfaction with search results Satisfaction with terminal display Satisfaction with online instructions, prompts, HELP messages Satisfaction with system response time Overall satisfaction with system Independent or "Predictor" Variables Type of search performed Professional role/occupation Primary use for information Frequency of library and catalog use Prior experience with other computer systems Age, sex, education Sample Search Experiment (n = 20) Comparison Search User Experiment Survey (n = 60) (n = 600 x x x x x x x x x x x x x *Variable manipulated by experimenter. x x x* x x x x x x x x x x x x x x x burden among participating patrons and staff; and weave across the three study methods a common thread of similarly worded questions relating to a core set of dependent and independent variables (i.e., measures defining the nature and extent of user acceptance of Systems A and B. and definable user attributes or behaviors thought to be potentially related to, or pre- dicting, user acceptance and system prefer- ence). Assigning these variables in an over- lapping fashion across the three study methods would, it was hoped, yield a high degree of confidence in the strength and re- liability of study findings obtained under different experimental conditions with dif- ferent user populations. Table 1 lists the study's dependent variables and selected in- dependent or predictor variables, and their respective usage in each of the three study methods. The approach taken is not unlike that advocated by Shneiderman, who makes a strong case for the use of controlled field experimentation in the study of human-computer interaction.6 METHODS AND PROCEDURES Data collection activities relating to the user acceptance dimension took five months, beginning with administration of 415 the System A User Survey of patrons and staff in late April and May; administration of the System B User Survey in early June through August; conduct of the Sample Search Experiment with staff in August; and conduct of the Comparison Search Ex- periment with patrons in September.* Technical performance testing was carried out by a separate data collection team dur- ing the period Ply through September. Assessing User Acceptance Sample Search Experiment The Sample Search Experiment pro- vided the most effective control over poten- tially confounding variables. In this experi- ment, a panel of twenty NLM professional staff, comprising librarians and nonlibrar- ians uninvolved in the development of ei- ther candidate system, was randomly se- *It should be noted that hardware downtime, both planned and unplanned, was the source of several interruptions to the data collection sched- ule. Prudent investigators will make allowances accordingly, especially when attempting to eval- uate prototype systems within an operational en- vironment containing a heavy service obligation. On the other hand, we were fortunate to experi- ence a minimum of disruptions due to software malfunctions.

416 ASSESSING MEDICAL TECHNOLOGY lected, assigned to one of two experimental conditions (odd/even), and scheduled for individual search sessions. Fourteen spe- cially selected paired search queries, simu- lating representative uses of an online cata- log across six common search types, were presented to each respondent for execution. Each sample search pair was selected from a larger group that had undergone thor- ough pretesting on both candidate systems using uninstructed searchers. Those as- signed to the "odd" condition performed the first half of the paired searches on Sys- tem A and the second on System B ("even" condition respondents used the two systems in reverse order), thus respondents did not repeat the same search query on both sys- tems. While the order of system use varied according to experimental condition, the order of search query pairs remained con- stant. Search query pairs were matched by type (i.e., personal and corporate author, conference, series, title, and subject), by level of search difficulty, and by size of the expected retrieval. Respondents were in- structed to base their judgments of retrieval relevance to post-1974 records to control for the unequal size of the two systems' database. Conduct of the Sample Search Experiment took place in the NLM's public catalog area where two adjacent terminals, separately hard-wired to the System A and System B hosts, were reserved for the exper- iment. Following execution of each search pair on Systems A and B. which was stopwatch-timed by the experimenter, the respondent was instructed to check rele- vant records on the hard-copy printouts re- trieved and to answer a series of structured questions dealing specifically with system preference when conducting that particu- lar type of search. Upon completion of all fourteen searches, global attitude measures of user satisfaction and comparative system preference were obtained. Individual, open-ended interviews, probing specifi user interface features liked and disliked, were also conducted by the experimenter.' The time burden for this in-depth system comparison was high, averaging 11/4 hours per respondent. Comparison Search Experiment In contrast to the more controlled but less realistic Sample Search Experiment, the Comparison Search Experiment served to maximize the authenticity of study con- ditions. In this experiment, sixty library pa- trons conducted a self-initiated search of their own choosing on both System A and System B. sequentially. The procedure was that patrons entering the public catalog area during randomly selected periods were asked to participate in the experi- ment; approximately 75 percent agreed to participate. Each was assigned to one of two odd/even experimental conditions; "odd" numbered respondents began their search on a terminal connected to System A and "even" numbered respondents started with System B. The experimenters, the same two-person team conducting the Sample Search Experiment, closely moni- tored the respondents' searches and re- corded them on hard-copy printouts for subsequent analysis. The experimenters de- termined when it was appropriate for re- spondents to switch systems and repeat their searches. They also conducted brief postsearch interviews with each respon- dent, using a subset of the same structured questions used in the Sample Search Exper- iment (see table 14. Total completion time for each respondent, including a short ori- entation to both systems, was under thirty minutes. User Survey The User Survey was intended to provide a detailed characterization of the informa- tion needs and behaviors of the NLM's com- puter catalog users and to indicate their ac- ceptance of each candidate system. A self-administered sixty-item survey ques- tionnaire, requiring fifteen minutes to complete, was given to all patrons and staff who conducted a computer catalog search during the test periods in which System A, and later System B. were available for use in the public catalog area. Initial plans to counterbalance the availability of Systems A and B (an ABBA design) and, thus, to help ensure equality of the two user sam- ples, were abandoned due to scheduling difficulties and the need to adhere to a tight study timetable. Also, the relatively limited number of visitors to the public catalog area precluded a sampling protocol for example, every tenth person if the quota of three hundred respondents per system

APPENDIX A: PROFILES was to be achieved. (A compliance rate in excess of 80 percent was a plus in this re- gard.) In all other respects, data collection procedures mirrored those established for the Council on Library Resources' (CLR) noncomparative study of fifteen online cat- alog systems.8 Use of the CLR instrument, slightly modified to provide more precise demographic data concerning NLM's user population, permits comparisons with the findings of that study. The companion CLR nonuser questionnaire was also ad- ministered to a sample of three hundred pa- trons who had not used either online cata- log. However, its principal value for the NLM study proved to be that of a control instrument, indicating that despite the nonrandom selection of catalog users sur- veyed, they did not differ appreciably from nonusers on such important demographic variables as professional role/occupation and frequency of library use. Assessing Technical Performance The assessment of system performance was intended to be a comprehensive and in- depth comparative examination covering all categories of system features and attri- butes: · database contents (e. g., number and type of records, currency) · composition of records (e. g., author, title, call number) · search/access (e. g., searchable data el- ements, indexes, truncation) · user cordiality (e. g., prompts, menus HELP messages, leniency of punctuation and spacing) · display (e. g., full and abbreviated rec- ords, paging forward and backward). Performance testing was carried out by a two-person team highly skilled in and knowledgeable about the technical aspects of cataloging and online searching and who were uninvolved in the design and develop- ment of System A and System B. Because these testing activities were time- consuming and physically fatiguing, they were carried out over an extended period. Results were periodically reviewed to re- solve discrepancies in findings and to en- sure consistent interpretation of the recom- mended procedures. 417 Verification Testing Using specially constructed verification protocols and checklists, each tester- independently of the other systematically exercised both systems so as to verify the presence or availability of all "required" and (selected) "necessary" system features and attributes, as specified by the study group. They also documented, with de- tailed annotation, the strengths and weak- nesses of each system with respect to the listed features and attributes. For example, in the course of obtaining information on the availability of prompts, the testers noted all junctures at which a system auto- matically generates prompts or HELP mes- sages and those which m ust be user- generated. Verification of user cordiality also included testers' comments on the ap- propriateness and clarity of all HELP mes- sages. Limits Testing Deliberately complex and ambiguous test queries were conducted for the purpose of "stressing" the limits of both systems in an effort to determine the systems' abilities to handle a variety of potential search prob- lems. These included common and com- pound surnames, incomplete titles, and long titles beginning with generic words. FINDINGS The results of technical performance testing were separately corroborated by a strong and consistent pattern of findings from the three studies of user acceptance. The major evaluation findings are summa- rized below:' · Users of the Com peter Catalog. Users of the online catalog at NLM (survey data merged for System A and System B users) represent a broad cross section of profes- sional roles and occupations: one-third stu- dents, one-quarter researchers, and one- tenth health care practitioners, with the remaining third distributed across several categories of ' other." Most users of the on- line catalog are infrequent visitors to the li- brary: 80 percent report visiting monthly or less often, and one-quarter are first-time visitors. This latter finding underscores the need for effective instructions, prompts,

418 ASSESSING MEDICAL TECHNOLOGY Table 2. Amount of Information Retreived when Using System A and System B Corresponding Questionnaire Items TO Respondents System A System B No Difference Sample Search Experiment (n = 20) "Considering only current items published since 1974, in general do you thinly you found more of the information you were looking for using . . ." Comparison Search Experiment (n = 35)* "Do you think you found more of the information you were looking for using . . ." user survey (n = 600) "In this computer search I found: More than/all that I was looking for . . . Some of what I was looking for . . . Nothing of what I was looking for . . ,, 75 S 20 71 18 SO 44 6 36 N/A 49 N/A 15 N/A *A total of sixty patrons participated in the Comparison Search Experiment; of these, thirty-five conducted subject searches and were asked this question. ~- and HELP messages, inasmuch as most cat- alog users will be novices. Such users are also unlikely to benefit from quick search techniques (i.e., use of a command lan- guage rather than menus) that are better suited to more practiced users. · Characteristics of Catalog Searches. Most online catalog users (53 percent) come with subject-related information, are look- ing for books on a topic (68 percent), and search by subject or topic (57 percent). This finding obtained in the User Survey and confirmed in the Comparison Search Ex- periment is consistent with other studies of computer catalog systems; it is inconsistent with studies of the conventional card cata- log that generally report a proportionately greater incidence of known-item search- ing."' This may well represent an instance in which the availability of a technology conducive to subject searching has brought about a behavior change in the user. · Online Catalog versus Card Catalog and COMCAT. The online catalog is clearly preferred to the library's card cata- log and computer output microform cata- log iCOMCAT). System A users preferred the computer catalog to the card catalog in higher numbers' with 91 percent of the Sys- tem A users surveyed rating it ''better," as compared to 76 percent of the System B users.* Among patrons who have used *All User Survey findings in which System A and . . System B are reported to differ have a statistical!! significant chi-square value of at least p >.001. COMCAT (S0 percent of those surveyed), preference for the computer catalog is equivalent for System A and System B us- ers, with 83 percent and 75 percent rating it as "better.'' · User Satisfaction with System A and System B. A consistent pattern of findings indicates that more information was gener- ally found by users of System A. As shown in table 2, 75 percent of staff users in the Sample Search Experiment and 71 percent of patrons in the Comparison Search Ex- periment selected the searches performed on System A as yielding more information. Similarly, 50 percent of the System A users as compared to only 36 percent of the Sys- tem B respondents in the User Survey indi- cated that they found "more than" or "all the information" that they were looking for. Satisfaction with search results was also higher among users of System A. Fifty-two percent of the patrons in the Comparison Search Experiment thought their search results were most satisfactory on System A, while 23 percent preferred System B and 25 percent indicated no difference. In the user survey' 62 percent of the System A users rated their search results as very satisfac- tory'- compared to 39 percent of the System B users; in the other extreme, only 4 percent of the System A users rated their search as very unsatisfactory'' compared to 10 per- cent of the System B users. Overall satisfaction was higher among System A users. As may be seen in table 3,

APPENDIX A: PROFILES Table 3. Overall Satisfaction with System A and System B Corresponding Questionnaire Items System A Sample Search Experiment (n = 20) "Overall, do you have a preference for . . ." % Respondents System B No Preference 60 15 25 Comparison Search Experiment (n = 60) "The next time you need to conduct a catalog search, will you want to use . . ." User Survey (n = 600) "My overall or general attitude toward the computer catalog is: Very Favorable . . . Somewhat Favorable . . . Somewhat Unfavorable . . . Very Unfavorable . . ." 55 20 25 84 65 13 22 N/A N/A N/A N/A 60 percent of Sample Seareh Experiment respondents expressed a moderate to strong preference for System A; only one-quarter of the staff persons queried expressed a preference for System B. Fifty-five percent of the patrons participating in the Compar- ison Seareh Experiment indicated that they "would use System A again," whereas 20 percent selected System B and 25 percent had no preference. In the User Survey, 84 percent of those who had used System A re- sponded that they had a "very favorable" attitude toward the computer catalog; in contrast only 65 percent of the System B us- ers did so. Whereas 13 percent of the Sys- tem B users surveyed indicated an unfavor- able overall attitude, less than 3 percent of the System A users expressed this view. What accounts for this observed prefer- enee for System A? The professional role or occupation of the user appears to be unre- lated to satisfaction with System A and Sys- tem B. In the Sample Search Experiment, preference for System A was equivalent for librarian and nonlibrarian staff persons. In the Comparison Search Experiment and in the User Survey, researchers, educators, practitioners, and students did not differ appreciably from one another in their pref- erenee for System A over System B. Other demographic variables thought to be po- tentially related to, or predicting, user ae- ceptance, and that were not found to be re- lated to satisfaction with one system as compared to the other, included such vari- ables as the intended use of the informa- tion, frequency of library use, frequency of card catalog use, previous computer experi- ence, age, gender, and education. 419 · Preferencefor System A/System B and Search Type. Preference for System A among patron and staff users is clearly re- lated to the type of search performed. Ta- ble 4 shows that two out of three respon- dents in the Sample Seareh Experiment thought that they "found the largest pro- portion of relevant information," and four out of five reported that their "search was easier" and "most satisfactory" using Sys- tem A to conduct subject searches. Signifi- eantly, only one of forty sample subject searches failed on System A; nearly half failed on System B. A sample search was termed a "failure" under one of two condi- tions: the searcher gave up, deciding to dis- eontinue searching for relevant records; or the search was terminated by the experi- menter, elapsed time having exceeded ten minutes. Among patrons conducting sub- jeet searches in the Comparison Seareh Ex- periment (see table 5), nearly three out of four favored System A, stating that they "found more information," that their search was "most satisfactory using [this system)," and that they "would use that sys- tem again." Postseareh interview eom- ments made by both patrons and staff indi- eated that system users were aware of the presence or absence of specific system inter- faee features that are supportive of subject searching and that they perceived them to be related to the conduct of a successful search. System A, for example, supports common treatment of controlled vocabu- lary and text word searching, an ability to search on multiple terms simultaneously, and provides for an automatic weighting and ranked display of closest matching

420 ASSESSING MEDICAL TECHNOLOGY Table 4. Acceptance of System A and System B among Staff Conducting Subject Searches in the Sample Search Experiment (n = 20) Dependent Variables and Corresponding Questionnaire Items Proportion of Retrieved Items Judged Relevant "Considering only current items published since 1974, of the information retrieved, would you say that the largest proportion of relevant information was found using To Respondents System A System B No Difference 65 10 25 Ease of System Use "In terms of user friendliness, did you find it easier to conduct this type of search ~subject] using . . ." Satisfaction with Search Results "In relation to what you were looking for, would you say that this type of search isubject] was most satisfactory using . . ." 80 10 10 80 5 15 Table 5. Acceptance of System A and System B among Patrons Conducting Subject Searches in the Comparison Search Experiment (n = 35)* Dependent Variables and Corresponding Questionnaire Items Amount of Information Retrieved "Do you think you found more of the information you were looking for using . . ." Ease of System Use "In general, did you find it easier to use . . ." Satisfaction with Search Results "In relation to what you were looking for, would you say your search was most satisfactory using . . ." 71 20 Overall Satisfaction with System "The next time you need to conduct a catalog search, will you want to use . . ." No Respondents System A System B No. Difference 71 18 11 46 1 1 43 66 14 20 *A total of sixty patrons participated in the Comparison Search Experiment; of these, fifteen persons limited their searching to known items only and are not included in this analysis. items by frequency of the search terms' oc- currence within the records. All are fea- tures demonstrated to be consistent with and supportive of user preferences and ac- tual searching behavior. Comparable find- ings favoring System A in performing subject-related searches were also obtained in the User Survey (see table 6~. In the present study, and as was reported in the CLR study, the most important determi- nant of user satisfaction with the online cat- alog is effective subject searching. In contrast to the clear preference for System A in performing subject searches, both systems were generally preferred equally well in performing known-item searches. A possible exception is the title search, due largely to the requirement that the System B user know the first word of the title sought. This restriction does not apply to System A in which a user may execute a multiword title search without regard to word order. Table 7 displays the verifica- tion testers' findings vis-a-vis system le- niency with regard to inconsistencies in syntax, including "order of words." The importance of this difference, observed and documented in verification testing, was subsequently corroborated by the finding that no title search failures occurred in the Sample Search Experiment using System A, whereas thirteen of twenty such searches failed on System B. · System A and System B Displays. A1- though substantially different in appear- ance, with System B emulating the conven-

APPENDIX A: PROFILES Table 6. Acceptance of the Online Catalog among User Survey Respondents Using System A (n = 222) and System B (n = 182) to Conduct Subject Searches Dependent Variables and Corresponding Questionnaire Items* Amount of Information Retrieved "In this computer search I found: To Respondents System A System B More than/all that I was looking for . . . 44 27 Nothing I was looking for . . ." 5 13 Satisfaction with Search Results "In relation to what I was looking for, this computer search was: Very Satisfactory . . . Very Unsatisfactory . . ." Overall Satisfaction with System "My overall or general attitude toward the computer catalog is: Very Favorable . . . Very Unfavorable . . ." Ease of System Use "A computer search by subject is difficult: Strongly Agree . . . Strongly Disagree . . . *Only "extreme" ratings are shown; total responses on these 4- and 5-point scales equal 100 To . 30 10 84 <1 61 6 6 12 36 21 Table 7. Technical Performance Testing: Excerpt From Verification Testers' Report* Feature/Attribute Status System A System B Comment System is lenient with regard to inconsistencies in syntax Spacing Required No No Punctuation Required No No Order of Required Yes—for subject and title No words searches. Completeness Required Yes of name Variant Required spelling System A: Will tolerate some inconsistencies in spacing and punctuation only in subject search. It is rigorous in requiring exact input for series, names, call numbers, etc. System B: Intolerant of . . . . . . 1nconslsrencles In spacing and punctuation for all searches except term (which must be single word). Yes—to (See truncation) Neither system will tolerate degree. incomplete terms imbedded in a name or series search, e.g., Natl. Lib. of Med. Yes—to a degree, only under subject search. Terms not found in the index are displayed to user for response—they may be retyped in case of typo or misspelling, or omitted from the search at the user's discretion. *The interested reader is referred to the study's technical report (Siegel. Online Catalog Study Final Report) for a detailed presentation of all available study data' including the results of technical performance testing as it relates to the ''required'' and necessary system features and attributes specified in the Study Group . 421

422 ASSESSING MEDICAL TECHNOLOGY tional card catalog image and System A utilizing a continuous "wraparound" array of record elements, both displays were found to be equally acceptable (or unac- ceptable) to patron and staff users. That is. just as many respondents in the Sample Search Experiment and the User Survey preferred one display format as the other. · Other Measures of User Acceptance. Although System A operates on a large mainframe computer and System B on a minicomputer, users were equally satisfied with computer response time on both sys- tems. User ratings and comments concern- ing the adequacy of online instructions, prompts, and"help" messages, however, suggest the need for additional work in this area, with System A's user aids being per- ceived as somewhat more effective. Fi- nally, Sample Search Experiment data per- taining to "number of known relevant items retrieved" and "time to complete search" were collected but only partially analyzed, inasmuch as preliminary exami- nation indicated their consistency with other dependent measures of user accep- tance favoring System A. CONCLUSIONS 1. From a methodological standpoint, the present study has demonstrated the fea- sibility of conducting an objective, com- parative evaluation of two prototype online catalog systems within the same library. The research strategy and methods devel- oped and used here should prove useful elsewhere in evaluating other patron acces- sible online information systems. 2. The study findings resulted in a deci- sion to adopt CITE (System A) for in-house use by the NLM's patrons and nontechnical staff. This decision was based on the deter- . Douglas Ferguson and others, "The CLR Public Online Catalog Study: An Over- view," Information Technology and Li- braries 1: 84-97 (June 1982); University of California, Division of Library Automation and Library Research and Analysis Group, Results of a National Survey of Users and mination that CITE has no critical short- comings and is essentially acceptable as is to the large majority of online catalog users at the NLM. ILS (System B) was also found to possess most system features and attributes required for an NLM-based online catalog. However, its performance on subject- related searches, an especially important requirement for online catalog users, was not equal to that of CITE. Specific sugges- tions for enhancing the user interface in this area (some of which had already been planned by the system designers) have been identified and documented. 3. While this evaluation study was de- signed primarily to provide an objective ba- sis for choosing among the candidate online catalog systems, it has also yielded impor- tant insight into catalog users' information needs and searching strategies. In this in- stance, it has provided an empirical basis for pursuing continued development of both systems. In the larger sense, it illus- trates the value of conducting formal evaluations with actual user groups—as a logical step within the overall system devel- opment process. ACKNOWLEDGMENTS This study involved the participation and close collaboration of many persons throughout the NLM, in particular, system designers Tamas Doszkocs and Charles Goldstein. Their contributions are grate- fully acknowledged. Special thanks is due Pauline Cochrane, Syracuse University, for her many helpful suggestions. Members of the Online Catalog Study Group were John Anderson, Clifford Bachrach, Lois Ann Colaianni, Karen Kameen, Henry Riecken, Warren Seibert, Manfred Waser- man, and Elliot R. Siegel (chair). REFERENCES Non- Users of Online Public Access Catalogs (final report to the Council on Library Re- sources, Berkeley: Univ. of California, Of- fice of the Assistant Vice President for Li- brary Plans and Policies, Nov. 1982). 2. Charles Hildreth, Online Public Access Cat- alogs: The user (Dublin, Ohio:

APPENDIX A: PROFILES OCLC, Inc., 1982). 3. Karen Markey, Online Catalog Use: Results of Surveys and Focus Group Interviews in Several Libraries (final report to the Council on Library Resources, V.2, Dublin, Ohio: OCLC, Inc., Mar. 1983), OCLC/OPR/RR- 8313. 4. NLM Online Catalog Study Group, "Re- quirements and Capabilities of an NLM- Based Online Catalog System" (unpublished report, Bethesda, Md.: National Library of Medicine, Feb. 1982). 5. Tamas E. Doszkocs, "CITE NLM: Natural Language Searching in an Online Catalog," Information Technology and Libraries 2:364-80 (Dec. 1983); Charles M. Gold- stein, Elizabeth A. Payne, and Richard S. Dick, The Integrated Library System (ILS;: System Overview (TR 81-05) (Bethesda, Md.: Lister Hill National Center for Biome- dical Communications, National Library of Medicine, July 1981), NTIS PB 81-188039. 6. Ben Shneiderman, "Fighting for the User: How to Test and Evaluate Human Perfor- mance with Information Systems," ASIS Bulletin 9: 27-29 (Dec. 1982~. 7. Copies of all data collection instruments can be found in Elliot R. Siegel, Online Catalog Study Final Report (Bethesda, Md.: Na- tional Library of Medicine, Dec. 1982), ERIC/IR ED 229 051. 8. Ferguson, "The CLR Online Catalog Study," Results of a National Survey of Users and Non- Users of Online Public Access Cata- logs. 9. The interested reader is referred to the study's technical report for a detailed presen- tation of all available study data: Siegel, On- line Catalog Study Final Report. 10. Pauline Atherton Cochrane, "Guest Edito- rial: A Paradigm Shift in Library Science," Information Technology and Libraries 2:3-4 (Mar. 1983). 11. Results of a National Survey of Users and Non-Users of Online Public Access Cata- logs. .. Copyright, 1984, American Library Association 423

Office of Technology Assessment Health Program Congress of the United States Washington, DC 20510 (202) 226 2070 Major Emphases of Technology Assessment Activities Concerns Technology Safety Efficacy/ Cost/ Cost-Effect/ Effectiveness Cost-Benefit X X X X X X X X X X Ethical/Legal/ Social Drugs Medical Devices/Equipment/Supplies Medical/Surg~cal Procedures Support Systems O rganizational/ Adm inistrative X X X X X X X X X Stage of Technologies Assessed X Emerg~ng/new X Accepted use X Possibly obsolete, outmoded Application of Technologies X Prevention X Diagnosis/screening X Treatment X Rehabilitation Assessment Methods Laboratory testing Clinical trials _ Epidemiological and other observational methods X Cost analyses Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $1,600,000 OFFICE OF TECHNOLOGY ASSESSMENT HEALTH PROGRAM Introduction The Office of Technology Assessment (OTA) is a nonpartisan analytical support agency which serves the U. S. Congress. OTA works directly with and for committees of Congress. It was authorized in 1972, funded in late 1973, and began full operations in 1974. OTA has three operating divisions: The Energy, Materials, and International Secu- rity Division; the Science, Information and Natural Resources Division; and the Health and Life Sciences Division. Within the Health and Life Sciences Division are three 424 programs: the Food and Renewable Re- sources Program; the Biological Applications Program; and the Health Program. This pro- file deals primarily with assessment activities of the Health Program. OTA is governed by a 12-member biparti- san congressional board of six senators and six representatives. The board is advised by an Advisory Council of 10 public members emi- nent in science, technology, and education, appointed by the board. The Comptroller General of the United States and the director of the Congressional Research Service of the Library of Congress are also members. The OTA director is appointed by the board and serves as a Nonvoting member. The director has full authority and responsibility for orga- nizing and managing OTA's resources ac-

APPENDIX A: PROFILES cording to board policies. OTA is currently funded at about $15.8 million per year, with a staff ceiling of 143. Assessments of health-related technologies have been conducted by OTA since its incep- tion. Established in 1975, the Health Pro- gram has issued reports on a wide variety of topics such as postmarketing surveillance of drugs, medical information systems, carcino- genesis testing technologies, technology for handicapped people, vaccine policies, the computed tomography (CT) scanner, the medical devices industry, tropical diseases, diagnosis-related groups (DRGs), and blood policy. Studies on generic issues related to so- cial impacts, efficacy and safety, and cost- effectiveness have also been conducted. Cur- rent topics of assessment include Indian health, physician payment,and techniques for measuring human mutations. OTA has several other important health- related activities. OTA was mandated by Congress to select and appoint the 15 mem- bers of the Prospective Payment Assessment Commission (ProPAC), which advises the secretary of DHHS regarding the hospital prospective payment system used for Medi- care. The appointments were first made in late 1983. OTA acts as an observer and evalu- ator of ProPAC, is to report annually to Con- gress on the functioning of the Commission, and is responsible for appointment of re- placement commissioners each year. OTA is mandated to approve the study protocol and monitor the conduct of the Veterans Admin- istration (VA) study of agent orange being carried out by the Centers for Disease Con- trol. OTA was also mandated to judge the feasibility of and study the protocol for the VA study of the health effects of exposure of servicemen to radiation from atomic bomb testing. Purpose The purpose of OTA is to help Congress anticipate and plan for the consequences of technological applications, and to examine the ways, expected and unexpected, in which technology affects people's lives. OTA clari- fies for Congress both the range of policy op- tions and the potential impacts of adopting 425 each option, but it makes no formal recom- mendations. OTA also provides advice to congressional committee members and staff, presents testimony at hearings, and conducts workshops with committees. Although OTA is responsible to the needs of the Congress and its products are designed for use by the Congress, they clearly have a much wider ap- plicability. Subjects of Assessment OTA Health Program evaluations have en- compassed a broad variety of technologies, including drugs, devices, procedures, and or- ganizational and support technologies used in diagnosis, prevention, and treatment and rehabilitation. OTA focuses its evaluation ef- forts on either generic technological issues (such as evaluation) or on case studies from which further research questions or general- izable lessons can be gained. Stage of Diffusion OTA Health Program evaluations have ad- dressed new, emerging, and widely accepted technologies. Concerns Compared to most medical technology as- sessment programs, the scope of OTA Health Program efforts is quite broad, reflecting the extent to which legislative policy issues are influenced by developments in technology. Assessments are primarily concerned with economic implications, cost, and cost-effec- tiveness of technologies, and are usually con- cerned with safety, effectiveness, and effi- cacy. Assessments also address cost-benefit, social, ethical, and legal aspects of technolo- gies where they are relevant. Requests Under OTA statute, studies may be initi- ated by a request from a chairman of a con- gressional committee, the OTA Congressio- nal Board, or the director of OTA. The congressional board approves all studies be- fore they are undertaken. The director of

426 OTA does have the authority to initiate small studies (under $30,000~. In addition, OTA will respond formally to requests for infor- mation from any member of Congress or anv Assessors congressional committee. In practice, OTA staff are very much involved in discussions with congressional staff, and study topics emerge from a continual iterative process. Selection The OTA Board decides whether or not OTA will undertake a requested assessment. First, the OTA staff screens the proposed study to determine what resources and time it might require and what modifications it might need to suit OTA's resources and con- gressional needs. The staff then presents a formal study proposal to the board, which makes the final decision. Process OTA generally does not support original research, but synthesizes existing knowledge from the medical and health policy literature with the help of expert advisers. OTA multi- disciplinary staff teams plan, direct, and draft all assessments. The teams rely exten- sively on the broad technical and professional resources of the private sector, including the universities, research organizations, indus- try, and public interest groups. The staff identifies and works with an expert advisory panel and consultants and contractors as ap- propriate, analyzes and integrates their work, and drafts the final report. The staff develops an initial draft with ad- vice from an expert advisory panel appointed for each main report, and then the draft is circulated for review and comment to groups and experts both in the government and in the private sector. Advisory panel assistance includes review and comment, although its consensus is not sought for report content or findings and reports are not formally ap- proved by the panels. Case studies of specific technologies have been used often in conjunc- tion with reports dealing with broad issues such as in studies of cost-effectiveness and cost-benefit analyses of technologies. Such case studies usually are prepared by experts ASSESSING MEDICAL TECHNOLOGY under commissions from the OTA and occa- sionally by OTA staff. The OTA Health Program has 13 perma- nent, multidisciplinary full-time staff, and approximately 12-14 other in-house staff on temporary appointments at any time. Out- side contract work is usually for special mate- rial to be included in OTA reports, such as appendixes to main reports, case studies, etc. OTA uses the expert advisory panels as a way of ensuring that reports are objective, fair, and authoritative. The Health Program is advised regarding overall planning by a standing 15-member Health Program Advi- sory Committee composed of experts in a va- riety of fields relevant to health care technol- ogy assessment. This committee generally is not involved directly in specific studies. The private sector is heavily involved in OTA studies as a source of expertise and per- spectives while an assessment is in progress. Contractors and consultants are drawn from industry, universities, private research orga- nizations, and public interest groups. OTA works to ensure that the views of the public are fairly reflected in its assessments. OTA involves the public in many ways through advisory panels, workshops, surveys, and formal and informal public meetings. Turnaround The bulk of OTA's work involves compre- hensive, in-depth assessments that may take 18 months or more to complete. It also pro- vides shorter responses to meet congressional needs, largely based on information in past and current assessments. OTA cap structure longer-range assessments so that the results, in various stages, can be sent to Congress in the form of interim reports. Reporting After a completed assessment has been ap- proved by the director of OTA, copies are sent to the. Technology Assessment Board. If a majority of the board does not object, the report is forwarded to the requesting con-

APPENDIX A: PROFILES gressional committeets), and summaries are sent to all members of Congress. The report and summary are then released to the public. OTA's reports are all published by the U. S. Government Printing Office, and are fre- quently reprinted by commercial publishers. Several hundred copies are ordinarily sent to people and organizations which OTA expects have interests in particular topics. Summar- TABLE A-14 OTA Health Program Reports 427 ies of all OTA reports are available free from OTA. Reports are released to the press with an accompanying press release. OTA studies are also available through the National Tech- nical Information Service. Table A-14 lists ti- tles of OTA Health Program main reports, technical memoranda, background papers, and health technology case studies. Main Reports Drug Bioequivalence. July 1974. Development of Medical Technology: Opportunities for Assessment. August 1976. Cancer Testing Technology and Saccharin. October 1977. Policy Implications of Medical Information Systems. November 1977. Policy Implications of the Computed Tomography Scanner. August 1978. Assessing the Efficacy and Safety of Medical Technol- ogies. September 1978. Selected Topics in Federal Health Statistics. June 1979. A Review of Selected Vaccine and Immunization Poli- cies Based on Case Studies of Pneumococcal Vac- cine. September 1979. Forecasts of Physician Supply and Requirements. April 1980. The Implications of Cost-Effectiveness Analysis of Medical Technology. August 1980. Assessment of Technologies for Determining Cancer Risks from the Environment. June 1981. Cost-Effectiveness Analysis of Inactivated Influenza Vaccine. December 1981. Technology and Handicapped People. May 1982. Strategies for Medical Technology Assessment. Sep- tember 1982. Medical Technology Under Proposals to Increase Competition in Health Care. October 1982. Postmarketing Surveillance of Prescription Drugs. November 1982. Medical Technology and Costs of the Medicare Pro- gram. July 1984. Federal Policies and the Medical Devices Industry. October 1984. Blood Policy and Technology. February 1985. Medical Devices and the Veterans Administration. February 1985. Preventing Illness and Injury in the Workplace. April 1985. Biomedical Research and Related Technology for Tropical Diseases. August 1985. Technical Memoranda Compensation for Vaccine-Related Injuries. Novem- ber 1980. Technology Transfer at the National Institutes of Health. March 1982. MEDLARS and Heath Information Policy. Septem- ber 1982. Diagnosis Related Groups (DRGs) and the Medicare Program: Implications for Medical Technology. July 1983. Quality and Relevance of Research and Related Activ- ities at the Gorgas Memorial Laboratory. August 1983. Scientific Validity of Polygraph Testing: A Research Review and Evaluation. November 1983. Update of Federal Policies Regarding the Use of Pneumococcal Vaccine. May 1984. Review of the Public Health Service's Response to AIDS. February 1985. Background Papers Computer Technology in Medical Education and As- sessment. September 1979. Methodological Issues and Literature Review. Sep- tember 1980. The Management of Health Care Technology in Ten Countries. October 1980. Policy Implications of Computed Tomography (CT) Scanner: An Update. January 1981. The Information Context of Premanufacture Notices. April 1983. The Impact of Randomized Clinical Trials on Health Policy and Medical Practice. August 1983. Case Study Series Case Study No. 1. Formal Analysis, Policy Formulation, and End- Stage Renal Disease. April 1981. 2. The Feasibility of Economic Evaluation of Diag- nostic Procedures: The Case of CT Scanning. April 1981. 3. Screening for Colon Cancer. April 1981. 4. Cost Effectiveness of Automated Multichannel Chemistry Analyzers. April 1981.

428 TABLE A-14 Continued ASSESSING MEDICAL TECHNOLOGY 5. Periodontal Disease: Assessing the Effectiveness and Costs of the Keyes Technique. May 1981. 6. The Cost Effectiveness of Bone Marrow Trans- plant Therapy and Its Policy Implications. May 1981. 7. Allocating Costs and Benefits in Disease Preven- tion. May 1981. 8. The Cost Effectiveness of Upper Gastrointestinal Endoscopy. May 1981. 9. The Artificial Heart: Cost, Risks, and Benefits. May 1982. 10. The Costs and Effectiveness of Neonatal Intensive Care. August 1981. 11. Benefit and Cost Analysis of Medical Interven- tions: The Case of Cimetidine and Peptic Ulcer Dis- ease. September 1981. 12. Assessing Selected Respiratory Therapy Modali- ties: Trends and Relative Costs in the Washington, D.C. Area. July 1981. 13. Cardiac Radionuclide Imaging and Cost Effec- tiveness. May 1982. 14. Cost Benefit/Cost Effectiveness of Medical Tech- nolog~es: A Case Study of Orthopedic Joint Implants. September 1981. 15. Elective Hysterectomy: Costs, Risks, and Bene- fits. October 1981. 16. The Costs and Effectiveness of Nurse Practition- ers. July 1981. 17. Surgery for Breast Cancer. October 1981. 18. The Efficacy and Cost Effectiveness of Psycho- therapy. October 1980. 19. Assessment of Four Common X-Ray Procedures. April 1982. 20. Mandatory Passive Restraint Systems in Automo- biles. September 1982. 21. Selected Telecommunications Devices for Hear- ing-Impaired Persons. December 1982. 22. The Effectiveness and Costs of Alcoholism Treat- ment. March 1983. 23. The Safety, Efficacy, and Cost Effectiveness of Therapeutic Apheresis. July 1983. 24. Variations in Hospital Length of Stay: Their Re- lationships to Health Outcomes. August 1983. 25. Technology and Learning Disabilities. December 1983. 26. Assistive Devices for Severe Speech Impairments. December 1983. 27. Nuclear Magnetic Resonance Imaging Technol- ogy: A Clinical Industrial, and Policy Analysis. Sep- tember 1984. 28. Intensive Care Units: Clinical Outcomes, Costs, and Decisionmaking. November 1984. 29. The Boston Elbow. November 1984. 30. Market for Wheelchairs: Innovation and Federal Policy. November 1984. 31. The Contact Lens Industry: Structure, Competi- tion, and Public Policy. December 1984. 32. The Hemodialysis Equipment and Disposables Industry. December 1984. 33. Technologies for Managing Urinary Inconti- nence. July 1985. 34. Cost-Effectiveness of Digital Subtraction Angiog- raphy in the Diagnosis of Cerebrovascular Disease. May 1985. NOTE: Also available is the booklet "Abstracts of Case Studies in the Health Technology Case Study Series," updated annually. Impact OTA reports have generally been well- received by Congress and the various sectors of the health care industry. Because of the nature of congressional decisions, it is diffi- cult to attribute legislative change or other congressional actions to any one factor. How- ever, there are some specific examples, such as the following: · Based in substantial part on data and analysis in OTA's cost-effectiveness analysis of pneumococcal vaccine, Congress amended the Social Security Act to pay for the vaccine under Medicare (the first such preventive measure covered). · In 1983, the administration requested no money for the Gorgas Memorial Institute (a private, but federally supported, tropical disease research laboratory in Panama). The Senate Appropriations Committee asked OTA to examine whether the zeroing out was justified on the basis of quality and relevance of Gorgas's research. (The General Account- ing Office tGAO] pursued a separate set of questions regarding the institute.) The OTA report indicated that Gorgas was a good value for the amount of federal support in terms of quality and relevance. Congress re- stored the funding for Gorgas and directed Gorgas to report back to it with its plan for addressing the shortcomings noted in the OTA and GAO reports. · OTA analysis was one of the elements used in developing the legislation for the Na- tional Center for Health Care Technology. A

APPENDIX A: PROFILES final draft of the OTA report Assessing the Efficacy and Safety of Medical Technologies was available during the course of the staff work and legislative deliberations. · The OTA study on the scientific status of polygraph validity has been used as a basis for strong oversight of the administration's directives concerning increased use of the polygraph for national security. Reassessment Reassessments would be made upon con- gressional request, especially for any signifi- cant level of resources to be devoted to such study. Substantial congressional staff interest led to the 1981 updating of the 1978 CT re- port. Similarly, a 1979 analysis of pneumo- coccal vaccine was updated by congressional request in May 1984, and the earlier OTA study on nurse practitioners is being updated and expanded at the request of the Senate Appropriations Committee. Other than those instances, there has not been significant in- terest in reassessment. Funding/Budget OTA is funded by direct congressional ap- propriation each year and does not accept funding from other sources. Program budgets at OTA change as new projects are approved and initiated. The FY 1985 budget for the 429 Health Program is approximately $1.6 mil- lion. Examples Due to their length, full OTA assessment reports are not included here. The following pages include summaries from the OTA case studies of assistive devices for severe speech impairments (1983), nuclear magnetic reso- nance (1984), intensive care units (1984), the Boston Elbow (1984), and the market for wheelchairs (1984~. Sources Behney, C. J., Health Program Manager, Congres- sional Office of Technology Assessment. 1985. Per- sonal communications. Gibbons, J. H. 1984. Technology Assessment for the Congress. The Bridge. Summer:2-8. Office of the Federal Register. 1982. The United States Government Manual 1982/83. Washington, D.C.: General Services Administration. OTA. 1982. What OTA Is, What OTA Does, How OTA Works. Washington, D.C. OTA. 1983. Health Technology Case Study 23: The Safety, Efficacy, and Cost Effectiveness of Ther- apeutic Apheresis. Washington D.C.: U.S. Govern- ment Printing Office. OTA. 1983. Assessment Activities: Current Proj- ects, Publications in Press, Recent Publications, Se- lected Publications of Interest. Washington, D.C. OTA. 1984. List of Publications. Washington, D.C.

430 ASSESSING MEDICAL TECHNOLOGY CASE STUDY #26 Assistive Devices for Severe Speech Impairments Lack of speech is a serious disability. When combined with other dis- abilities that render a person functionally unable to write or type, it is more serious still. Whatever their age and whether or not they are of normal in- telligence, people with such disabilities are very likely to be placed in in- stitutional care. And if they are people who—because of a genetic defect, an accident during gestation or an injury at birth have never talked, chances are they will be assumed to be profoundly mentally retarded and so will also have been deprived of that education without which no one in this society can aspire to enter the work force or to live as an independ- ent adult. As recently as the mid-1970's, there was little or no remedy for either the congenital or the acquired inability to speak when accompanied by severe physical disability. Affected individuals could often communicate with those in their immediate circles by resorting to eye signals, other forms of private language, or the use of primitive language boards. But the emo- tional and intellectual content of such interactions was limited, consigning these people to social isolation, passivity, and custodial care. This case study is about the revolution in communication aids that has since changed the outlook for this population, its accomplishments to date, its promise for the future, and its problems. It also discusses related public policy and the barriers to fully utilizing the technology now available for the benefit of the individuals in question, their friends and families, and society as a whole. Prepared by: Judith Randall Published in December 1983 as Case Study #26 (50 pp., 52 refs.). Associated main report was Office of Technology Assessment, U.S. Congress, Technology and Handicapped People (Washington, D.C.: U.S. Government Printing Office, May 1982). Available from: U.S. Government Printing Office, stock #052 003-00940-4, $2.50. CASE STUDY #27 Nuclear Magnetic Resonance Imaging Technology: A Clinical, Industrial, and Policy Analysis The case study entitled "Nuclear Magnetic Resonance Imaging Technol- ogy: A Clinical, Industrial, and Policy Analysis" provides a "snapshot" view of the scientific and clinical status of nuclear magnetic resonance (NMR) imaging, as well as an overview and analysis of the impact of various Federal and non-Federal policies and practices on the development and diffusion of NMR imagers as of August 1984. The policies examined include the Food and L)rug Administration (FDA) premarket approval (PMA) process; Health Care Financing Administration (HCFA), Blue Cross/Blue Shield (BC/BS>, and commercial insurance company reimbursement decisions; State certificate-of-need (CON) policies, and Federal financial support for research and development.

APPENDIX A: PROFILES NMR imaging is an exciting new diagnostic imaging modality that has captured the interest of the medical and scientific communities and the gen- eral public. NMR imagers employ radiowaves and magnetic fields rather than ionizing radiation, thus eliminating the risk of X-irradiation associated with use of devices such as X-ray computed tomography (CT) scanners. NMR imagers not only produce images with excellent spatial and contrast resolution without the need for injection of potentially toxic contrast agents, but also enable physicians to visualize areas such as the posterior fossa, brain stem, and spinal cord that until now have not been well seen with other noninvasive imaging techniques. In addition, because NMR imagers are sensitive to fundamental physical and chemical characteristics of cells, the technique offers the possibility of detecting diseases at earlier stages than is currently possible and of permitting accurate diagnoses to be made non- · · . nvaslvely. NMR imagers are diffusing very rapidly. In January 1983, 14 units were installed in the United States. By October 1983, 34 units were in place in the United States, and by August 1984, at least 145 units had been installed worldwide, of which 93 were in the United States. NMR imagers are the first imaging devices for which FDA premarket ap- proval has been required under the 1976 Medical Device Amendments. In the case of NMR, the PMA process appears to be playing primarily a quality assurance role. PMA does not appear to have constrained NMR techno- logical development or the number of NMR imagers that could be installed in the United States on an experimental basis. The PMA process may prove capable of conferring an important competitive advantage upon those man- ufacturers who are first to receive PMA, a possibility which could affect the speed with which manufacturers pursue development of new technol- ogies in the future. Third-party payers are now in a position of major influence over the rate at which NMR imagers are acquired. Although some local BC/BS plans and some commercial insurers have begun to pay for NMR scans, neither HCFA nor national BC/BS have completed the assessments that will deter- mine their payment policies and recommendations. Delays in reimburse- ment coverage will slow diffusion of NMR imagers. Future HCFA decisions regarding recalibration of diagnosis related groups (DRG) payment rates as part of Medicare's prospective hospital payment system will also affect hospital decisions regarding acquisition of NMR scanners in the future. State CON policies appear to be having several effects on the diffusion of NMR imagers. They are delaying the acquisition of NMR devices by some hospitals, speeding acquisition by others, and promoting the place- ment of NMR imagers in outpatient diagnostic centers, which are not sub- ject to the same CON controls as hospitals. The status of State CON pol- icies and decisions is reviewed in the case study. Prepared by: Earl P. Steinberg and Alan B. Cohen. Published in September 1984 as Case Study #27 (156 pp., 207 refs.). Associated main report was Office of Technology Assess meet, U.S. Congress, Federal Policies and the Medical Devices Industry (Wash- ington, D.C.: U.S. Government Printing Office, October 1984). Available from: U.S. Government Printing Office, stock #052403 00961-7, $5.50. . 431

432 ASSESSING MEDICAL TECHNOLOGY CASE STUDY #28 Intensive Care Units: Costs, Outcome, and Decisionmaking This case study was prepared as part of OTA's project on "Medical Tech- nology and Costs of the Medicare Program." This case study provides an overview of the development of intensive care units (ICU) and their rapid diffusion into medical practice. It presents information on their utilization costs and reimbursement. It also describes various measures of outcomes of intensive care and reviews the outcome literature. Finally, the intricacies of decisionmaking in the ICU are discussed, and policy implications are presented. Almost 80 percent of short-term general hospitals have at least one in- tensive care unit. Overall, in 1982, 5.9 percent of total hospital beds in non- Federal, short-term community hospitals were beds in intensive and cor- onary care units. Over the 6 years to 1982, the number of ICU beds rose about 5 percent a year, compared to a rise in general hospital beds of only 1 percent a year. For a number of reasons, an accurate estimate of the national cost of ICU care is difficult to make. The national average per diem charge in 1982 was $408 compared to a regular bed per diem charge of $167, a ratio of about 2.5:1. However, it is likely that the true cost ratio is closer to 3.5:1. In addition, ICU patients consume a greater proportion of ancillary serv- ices than patients on regular floors. Based on these and other considera- tions, it is estimated that the costs of adult intensive care the cost to the hospital of patients while they are in the intensive care unit represents about 14 to 17 percent of total inpatient, community hospital costs, or $13 billion to $15 billion in 1982. Inclusion of the other types of specialized, intensive care units, such as burn units and neonatal intensive care units, would bring the percentage of total inpatient hospital costs attributable to intensive care to about 20 percent. Unfortunately, it is difficult to separate the intensity of care from the setting in which it is provided, and therefore, to know whether intensive care would be as effective if provided on the general medical floor as on the physically and administratively separate ICU. A recent consensus panel sponsored by the National Institutes of Health found that it is impossible to generalize about whether ICU care improves outcome for the varied ICU patient population. Nevertheless, for most severely ill and injured patients, care in an ICU has become the accepted and standard mode of treatment in the United States. The representation of the elderly in ICUs seems to be the same or slightly more than in the hospital as a whole. Poor chronic health status, rather than age, appears to be a predominant factor that limits the use of ICUs in individual cases in the United States.

APPENDIX A: PROFILES . 433 Recent data have emphasized the inverse relationship between the cost of care and survival. At this time, there are no accepted methods for deter- mining ahead of time which patients will benefit from additional ICU care. From a number of studies it is clear that the sickest ICU patients, many of whom do not survive consume a highly disproportionate share of ICU costs. Under the new Medicare prospective pricing payment system, based on diagnosis-related groups (DRGs), the sicker ICU patients will become fi- nancial "losers" to the hospital. Yet, the new incentives of the DRG pay- ment system are being imposed on a decisionmaking environment in which the cost of ICU care has been of relatively minor concern. Indeed, the tradi- tional decisionmaking process related to ICU patients has often led physi- cians to provide ongoing intensive care after the initial rationale for doing so no longer exists. The relatively recent concern about health care costs as well as the increasing desire by patients and families to forego life-sus- taining treatment In some situations may alter prevailing provider attitudes regarding provision of intensive care. ICU decisionmaking will become even more difficult than it has in the past due to potential financial, moral, and ethical conflicts between patients, physicians and hospitals. Prepared by: Robert Berenson. Published in November 1984 as Case Study #28. Associated main report was Office of Technology Asessment, U.S. Congress, Medical Tech- nologyandCostsoftheMedicareProgram (Washington, D.C.: U.S. Govern- ment Printing Office, July 1984). Available from: U.S. Government Printing Office, contact OTA Publishing Office for price information (202/224-8996).

434 ASSESSING MEDICAL TECHNOLOGY CASE STUDY #29 The Boston Elbow The Boston Elbow is an artificial arm, battery-powered and myoelec- tr~cally controlled i.e., controlled by signals from an amputee's stump muscles. It reproduces one active movement of the human arm, elbow flex- ion and extension. The Boston Elbow is technologically distinctive, but it is only one way to compensate for the loss of an arm. Nonprosthetic measures as well as competing prostheses are available to most amputees. Distribution of the Boston Elbow and other compensatory options is at least in part a function of public policy, especially the design and imple- mentation of disability benefits programs. For policy purposes, people (ex- cluding children) with disabilities seem to fall into three groups veterans, workers, and citizens each with eligibility criteria set by law. The amputee- veteran has many alternatives to the Boston Elbow, including an elbow pros- thesis that originated at the Veterans Administration. The amputee-worker faces three sets of circumstances: · If injured in the workplace, he or she is eligible for workers' compen- sation benefits, including monetary compensation and prosthetic devices. Amputees are most likely to be fitted with a Boston Elbow if their employer's insurer is the Liberty Mutual Insurance Co.; Liberty Mutual financed design of the device and continues to develop and manufac- ture it. · Workers with long-term clisabilities who have paid into the Social Secu- rity system receive Disability Insurance benefits in the form of cash payments and Medicare program coverage. The latter may provide a Boston Elbow, but program coverage becomes a benefit only 24 months after the onset of disability. Disabled individuals judged to be potential workers are entitled to enter the Federal/State Vocational Rehabilitation Program and receive the serv- ices required for their rehabilitation. Potential workers are thus entitled to a Boston Elbow, but they must compete for limited Vocational Rehabilita- tion moneys. The amputee-citizen is unlikely to be provided with a Boston Elbow, but Federal policies do create relevant research by the National In- stitute of Handicapped Research, regulation by the Food and Drug Admin- istration, and legislated restatements of disability issues, such as the Rehabilitation Act of 1973. The Boston Elbow fares differently in different programs, and although this can be difficult for the amputee, it is the re- sult of explicit mandates, institutional histories, and ongoing allocation of public resources. Prepared by: Sandra J. Tanenbaum. Published in November 1984 as Case Study #29. Asso- ciated main report was Office of Technology Assessment, U.S. Congress, Federal Policies and the Medical Devices Industry (Washington D.C.: U.S. Government Printing Office, October 1984) Available from: U.S. Government Printing Office, contact OTA Publishing Office for price information (202/224-8996). .

APPENDIX A: PROFILES CASE STUDY #30 The Market for Wheelchairs: Innovations and Fecleral Policy Wheelchairs, for many disabled persons, are essential medical devices for work, mobility, and recreation. The characteristics, prices, and durabil- ity of these chairs are critical both to the quality of life of their users and to the costs incurred by the users, insurers, and government agencies. This case study focuses on how Federal policies affect innovations in wheelchair characteristics. The case study examines the wheelchair market and notes that one Amer- ican in 200 (approximately 1.2 million total in 1977) is a wheelchair user. In 1982, an estimated 338,000 wheelchairs of all types were sold in the United States, for total retail sales of $126 million. The market is dominated by a few large firms, which suggests that the wheelchair market is oligopolistic. Purchase costs of a wheelchair vary from $200 to $3,000, depending on the type of wheelchair (manual, power, sports, or power alternative), the number of accessories and custom features, the quality of the construction and materials, and the manufacturer. Maintenance and repair costs of wheelchairs are substantial. Over an average 3- to 4-year wheelchair lifetime, cumulative repair costs are sometimes more than initial purchase costs. The study compares the costs of different wheelchair models using total an- nualized costs. The wheelchair market is dominated by third-party reimbursement. About half of all wheelchair purchases are at least partially funded by gov- ernment and another 40 to 45 percent by private insurers. Only 5 to 10 percent are paid for totally by the user. The extensive amount of third- party reimbursement steers innovation to devices that can expect to receive such funds. Although all insurers will pay for a wheelchair that is "medically necessary," the meaning of this term and insurers' policies vary. The emphasis on price over performance in the reimbursement procedures for general manual wheelchairs has probably discouraged innovation. The case study also discusses Federal policies relating to wheelchairs. Gov- ernment research and development efforts on wheelchairs appear modest in relation to the number of users. However, the Federal Government is a major purchaser of wheelchairs through the Veterans Administration, Medicaid, and Medicare. Wheelchairs themselves are covered under legislation concerning medical devices. The Food and Drug Administration classifies and regulates the marketing of medical devices, including wheelchairs. Eleven wheelchair manufacturers were surveyed by telephone interview regarding their innovations in the last decade, their research and develop- ment efforts, their marketing methods, and the effect of government pol- icies upon their operations. The results indicated that most innovations have been refinements of existing products, with an emphasis on usefulness to active users. 435

436 ASSESSING MEDICAL TECHNOLOGY The case study also presents two examples of innovations in wheelchair design, the Power Rolls(3 IV, made by Invacare Corp., and a curb-climb- ing wheelchair available in parts of Europe, but not the United States. Finally, public policy issues related to the wheelchair industry are discussed. Prepared by: Donald S. Shepard and Sarita L. Karon. Published in November 1984 as Case Study #30. Associated main report was: Office of Technology Assessment, U.S. Congress, Federal Policies and the Medical Devices Industry (Washington, DC: U.S. Government Printing Office, October 1984). Available from: U.S. Government Printing Office, contact OTA Publishing Office for price information (202/224-8996).

Prospective Payment Assessment Commission 300 7th Street, S.W., Suite 30IB Washington, DC 20024 (202) 453 3986 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X X X X X X X X X X Ethical/Legal/ Social X X Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X X X X X Stage of Technologies Assessed X Emerging/new X Accepted use X Possibly obsolete, outmoded Application of Technologies Prevention X Diagnosis/screening X Treatment X Rehabilitation Assessment Methods Laboratory testing * Clinical trials * Epidemiological and other observational methods X Cost analyses Simulation/modeling X Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $3,100,000t * ProPAC has the authority to collect original data using these methods, but has not done so thus far. r This amount constitutes the full ProPAC budget for FY 1985, including funds for technology assessment and other ProPAC functions. It includes $2.4 million in the FY 1985 budget, plus $0.7 million carried over from the FY 1984 budget. PROSPECTIVE PAYMENT ASSESSMENT COMMISSION Introduction The Prospective Payment Assessment Commission (ProPAC) was established by Congress under the Social Security Act Amendments of 1983 (P.L. 98-21), when the new Medicare prospective payment system was enacted. ProPAC was established as a permanent, independent commission of the 437 legislative branch of governments to advise and assist the Congress and the secretary of the Department of Health and Human Ser- vices (DHHS) in maintaining and updating ~ The intent of the original statutory language re- garding the placement of ProPAC in the Legislative Branch of government rather than the Executive Branch has been subject to some controversy between the Congressional Office of Technology Assessment

438 the Medicare prospective payment system (PPS). Under PPS, Medicare pays a predeter- mined, fixed amount per hospital inpatient discharge. This amount is determined in ad- vance (i.e., prospectively) for each type of case based on the classification system in which patient diagnoses are categorized into 468 diagnosis-related groups (DRGs). (Two additional DRGs are used for administrative purposes.) If a hospital's costs are less than the payment, it may keep the profit; if costs exceed payments, the hospital must absorb the loss. PPS replaces a retrospective, cost- based payment method in which hospitals es- sentially were reimbursed for most costs in- curred in providing hospital inpatient care to Medicare beneficiaries. Implementation of PPS began in October 1983 with individual hospitals' accounting years, to be phased in over 3 years, during which a hospital's payments are based on a combination of its own experience, the aver- age of hospitals in its census division, and the average of hospitals nationwide. During the first year, a hospital's payment reflected its own cost experience most strongly with some contribution of the experience of other hospi- tals in its region. In the next 2 years, the pay- ments are based on a decreasing percentage of a hospital's experience with increasing contributions of regional and national aver- ages. For hospitals' fiscal years starting on or after October 1, 1986, payments are to be based only on the national standardized amount. The PPS payment rates will be updated each year by the Department of Health and Human Services. For the FY 1984 and 1985 DRG rates, the law stipulated that DHHS in- crease the rates by the "hospital market- basket," i.e., a measure of price changes for the goods and services hospitals use to pro- and congressional staffers, and the Office of Manage- ment and Budget in the Executive Branch. At present, the opinion of the ProPAC and OTA general counsels that Congress intended ProPAC to be placed in the Legislative Branch prevails. Language in the Deficit Reduction Act of 1984 and letters from Senator Dole and Congressman Rostenkowski further clarify the matter. See OTA (1985) for discussion of this matter. ASSESSING MEDICAL TECHNOLOGY duce care, plus a 1 percent "discretionary ad- justment factor" that was subsequently low- ered to 0.25 percent by the Deficit Reduction Act of 1984. Starting in FY 1986, DHHS is to have the discretion to modify the payment rates annually by any amount. The discre- tionary adjustment factor will take into ac- count such elements as hospital productivity, changes in the hospital product, and techno- logical advances. DHHS is to adjust the DRG classifications and weighting factors for FY 1986 and at least every 4 years thereafter to reflect changes in treatment patterns, technology, and other factors that may change the rela- tive use of hospital resources. The reclassifi- cation of DRGs may include the establish- ment of new DRGs. The weighting factor for each DRG is to reflect the relative hospital re- sources required for the diagnoses included in that DRG, compared to those classified in other DRGs. Given the far-reaching effects of PPS on the health care system and Medicare benefi- ciaries, Congress thought that an indepen- dent body ProPAC was needed for assist- ing in updating and maintaining the new payment system. ProPAC also was designed to assist in addressing questions that were previously of lesser priority, such as what rea- sons are behind variation of medical practice across the country and which new technolo- gies should be included in the system. Purpose The formal responsibilities of ProPAC are mandated by law. * The primary responsibil- ities of ProPAC are (1) recommending annu- ally to the secretary of DHHS the appropriate percentage change in the payments made un- der Medicare for inpatient hospital care, and (2) consulting with and recommending to * ProPAC's responsibilities are set forth in Section 1886 of the Social Security Act as amended by P.L. 98-21, and by P.L. 98-369, the Deficit Reduction Act of 1984. Further responsibilities are set forth in the re- port of the House Appropriations Committee, House Report No. 911, 98th Congress., 2d Sess. (1984) 139,140, accompanying the appropriations legislation for ProPAC for FY 1985, P.L. 98-619.

APPENDIX A: PROFILES DHHS and reporting to Congress necessary changes in the DRGs including reclassifying DRGs and changing their relative weights. ProPAC is also required to evaluate adjust- ments in the DRG system made by DHHS and to report its findings to Congress. The Deficit Reduction Act of 1984 (P.L. tion 98-369) gave ProPAC two additional specific tasks: (1) to study cardiac pacemakers and the relative weights assigned to those DRGs in which pacemakers are used, and (2) to make a recommendation regarding the over- all annual rate of increase for non-PPS hospi- tals. Finally, in 1984 the House Appropriations Committee set forth ProPAC's role as evalua- tor of the impact of P.L. 98-21 on the Ameri- can health care system. ProPAC was there- fore directed to submit an annual report to Congress expressing its views on this broader matter. Other responsibilities will be pursued to the limit of available staff and resources. ProPAC is not an appeals body and has no regulatory functions. ProPAC does not make . . coverage c eclslons. Subjects of Assessment A critical area of ProPAC responsibility is to evaluate and make recommendations re- garding an administrative technology, i.e., prospective payment using diagnosis-related groups for inpatient hospital services. In or- der to advise DHHS regarding PPS payment rates and DRG classification and weighting, ProPAC may evaluate drugs, medical de- vices, medical and surgical procedures, sup- port systems, and various organizational and administrative aspects of health care. Technologies that may have important ef- fects on hospital inpatient reimbursement will be selected for consideration by ProPAC. The technologies and diagnoses considered thus far by ProPAC (in particular by its Sub- committee on Diagnostic and Therapeutic Practices) are the following. In-depth analyses for April 1985 report to DHHS: · intraocular lens implants · percutaneous transluminal coronary an- gioplasty · cardiac pacemaker implantation 439 In-depth analyses in 1985 (no recommenda- tion in April 1985 report): · cyclosporine use in renal transplantation magnetic resonance imaging dual joint procedures in one hospitaliza- treatment for alcohol dependence cochlear implants extracorporeal shock wave lithotripsy dermatologic disorders Considered, but no in-depth analyses planned at present (a decision for no recom- mendation was made): · bone marrow transplantation · treatment for infective endocarditis · treatment for cystic fibrosis Stage of Diffusion ProPAC may examine technologies that are new, emerging, in accepted use, and those that may be obsolete. Concerns ProPAC is required to collect and assess in- formation on the safety, efficacy, and cost- effectiveness of technologies in order to carry out its responsibility to identify medically ap- propriate patterns of health resources use. It is also to take into account the hospital mar- ket basket of goods and services that hospitals purchase, hospital productivity, length of hospitalization, technological and scientific advances, quality of care provided in hospi- tals, site of service delivery (e.g., outpatient versus inpatient), and regional variation in medical practice patterns and resource utili- zation. ProPAC's information needs and work fo- cus on changes—both general and specific- in the delivery of hospital services to Medi- care patients. The changes occurring in medical and hospital service delivery must be identified and reflected in ProPAC's recom- mendations regarding the appropriate per- centage change in Medicare payments and the DRG classification and weighting sys- tem. Adjustments may be needed due to new technologies that may be costly but quality

440 enhancing, or because a technology is becom- ing obsolete and its cost may exceed its value. ProPAC will consider the issue of appro- priate reimbursement levels for technologies as they diffuse into wider use. (The initial costs for emerging technologies are often high, reflecting the investment in research and development. However, contrary to what might be expected under market forces, the price tags on these technologies, once es- tablished, generally have not gone down, even though the technologies become more widely applied by providers who did not make the initial investments in research and development. ~ To the extent that DHHS and Congress ac- cept ProPAC's recommendations regarding the PPS, ProPAC's decisions may have signif- icant ethical, legal, and social implications. Because of the magnitude of the Medicare program, and because most other third-party payers Medicaid, commercial insurers, and others closely observe Medicare when mak- ing their own coverage decisions, Medicare policies regarding coverage for medical tech- nologies may have sweeping effects on partic- ular groups of people. As in the exemplary case of the federal end-stage renal disease program begun in 1972, major third-party payer coverage of new technologies may make these widely available where they had not been before. Eligibility for coverage by various third-party payers varies according to such factors as age, income, and employ- ment status, so coverage decisions may affect groups of people along these lines. Thus, when considering the role of certain technol- ogies in the configuration of the PPS and the future of the system itself ProPAC may take into account certain ethical, legal, and social consequences. Requests Issues for ProPAC consideration may be suggested by outside parties such as medical specialty societies, the hospital industry, the medical products industry, Congress, and staff and commission members. Notices in the Federal Register solicit various types of input from the public. The commission en- courages consumers, hospitals, physicians, ASSESSING MEDICAL TECHNOLOGY business firms, and other individuals and groups to submit information in writing con- cerning medical and surgical procedures, ser- vices, practices, and technologies, or other information relevant to its responsibilities. Selection ProPAC usually operates within a struc- ture in which issues and information are brought by staff to the attention of appropri- ate ProPAC subcommittees, and then brought to the attention of the full commis- sion. Candidate assessment topics are first screened by ProPAC staff before being ad- dressed by the commission, as described be- low. Process The flow of work at ProPAC generally pro- ceeds from staff to subcommittee to full com- mission for final approval. Methods used thus far have been literature syntheses, consulta- tion of experts, various cost and other data analyses and informal group judgments. ProPAC is to use existing information and its staff for analysis to the fullest extent possi- ble. Where information is inadequate and where the desired scope of analysis exceeds staff capabilities, ProPAC has the authority to carry out, or award grants or contracts for, original research and experimentation, in- cluding clinical research, in order to meet specific needs for making well-informed rec- ommendations. However, the commission has neither plans nor the budget for any clini- cal research at this time. To date, three subcommittees have been appointed. The Diagnostic and Therapeutic Practices Subcommittee is responsible for as- sessing individual technologies and making the recommendations regarding DRG classi- fication and weights. In the conduct of its work, it will assess the safety, efficacy, and relative cost-effectiveness of technologies. Special attention will be given to revising the DRG system to reflect appropriate differ- ences in hospital resource consumption that result from changing health care practices. This subcommittee uses a two-step process for evaluating diagnostic and therapeutic

APPENDIX A: PROFILES technologies and their relationship to the DRG system. The first step is a screening analysis in which ProPAC staff summarizes available information regarding a specific technology for safety, efficacy, practice pat- terns, affected populations, costs, quality, availability of data, and current DRG classi- fication and weighting. The second step is an in-depth analysis by the subcommittee and staff of options that could be used to decide whether changes should be recommended in the DRGs. The Hospital Productivity and Cost-Effec- tiveness Subcommittee is responsible for making the annual update factor recommen- dations. This subcommittee has concentrated its work in two areas: the hospital market basket of goods and services and the discre- tionary adjustment factor. It will determine indicators of change and measures of produc- tivity to be considered in determining the overall rate of change for inpatient pay- ments. It is to identify and examine changes in staffing arrangements, type and patterns of service delivery, lengths of hospitalization, and other issues related to productivity and cost of care. The Data Development and Research Sub- committee has assumed responsibility for or- ganizing the outside research agenda. It will identify data needs and availability of data sources relevant to the commission's responsi- bilities. Data sources will be evaluated ac- cording to such standards as reliability and validity of information and generalizability of results. It is also responsible for developing an analytic plan for areas in which data are needed but unavailable. The subcommittee has developed a candidate list of extramural research topics. The subcommittee will seek to ensure that research projects are timely enough to assist the commission on DRG re- calibrating and reweighting, on the overall system update factor, and on its report on the effects of PPS on the health care system. . Assessors The commission has 15 members ap- pointed to staggered 3-year terms by the Director of the Congressional Office of Technology Assessment (OTA). ProPAC 441 commissioners were first appointed in No- vember 1983. The membership is to have ex- pertise and experience in the provision and fi- nancing of health care, including physicians and nurses, employers, third-party payers, researchers in health services and health eco- nomics, and research and development of health care technologies. Nominations are accepted from national organizations of phy- sicians and other health care providers, hos- pitals, health care product manufacturers, business, health benefits programs, labor, the elderly, and other sources. By statute, the commission is to be assisted in its work by a staff of not more than 25, which is the current size of the ProPAC staff. The staff has two physicians (including the director) and members with backgrounds in nursing, statistics, hospital financial manage- ment, health services research, public health, economics, public policy, law, biomedical engineering, and medical records. Staff members have held previous positions with the Health Care Financing Administration, Food and Drug Administration, National Center for Health Care Technology, Na- tional Center for Health Services Research, Office of the DHHS Secretary, Office of the Assistant Secretary for Health, the Veterans Administration, various congressional offices and other federal agencies, institutional pro- vider organizations, the medical product in- dustry, and private third-party payers. Turnaround The turnaround time for ProPAC reports may vary from several months to more than a year. The commission's reports of recommen- dations for adjusting PPS are due annually, in accordance with the statute. The cardiac pacemaker report was delivered on time on March 1, 1985, as specified in the Deficit Re- duction Act passed less than 8 months earlier. The period between statutorily mandated DRG recalibrations has raised an important consideration for ProPAC regarding the dif- fusion of new technologies. By law, recali- brations are to occur at least every 4 years, and they may be more frequent. DRG lag re- fers to the period of time between the avail- ability of a new technology in the market-

442 place and the reflection in DRG payment rates of its effect on the cost of delivering health care. DRG recalibrations are neces- sarily based on historical data. If DRG pay- ment rates are recalibrated no more fre- quently than every 4 years, hospitals may face having to wait several years before the acquisition of new technology may be re- warded by a concomitant increase in the ap- propriate DRG payment rate. The prospect of such lags may affect the diffusion of new, cost-raising technologies (see, e. g., Anderson and Steinberg, 1984~. ProPAC will consider a number of strategies for addressing DRG lag. These might include a fund that would allow the technology a temporary payment for a period of time, or a transitional DRG that evaporates within a specified period of time. Reporting The first full report of ProPAC, with rec- ommendations to the secretary of DHHS re- garding the percentage change in the pay- ments made under Medicare for inpatient hospital care and changes in the DRGs, was submitted April 1, 1985. It included a recom- mendation regarding the overall annual rate of increase for non-PPS hospitals. The car- diac pacemaker study was submitted on March 1, 1985. By late 1985, ProPAC will evaluate and report to Congress regarding the adjustments actually made by DHHS in the PPS. A third major report on the impact of PPS on the American health care system, requested by the House Committee on Ap- propriations, is scheduled to be completed by February 1986 and every year thereafter. These reports are to be made available to the public. ProPAC maintains a mailing list in order to keep the interested public informed of its meeting and other activities. Meetings of the commission are held every 2 to 3 months and are open to the public. Impact The director of OTA reports at least annu- ally to Congress on the activities of ProPAC. The first such report was made available in March 1985. In it, OTA concluded that in its ASSESSING MEDICAL TECHNOLOGY first year of operation, ProPAC's overall per- formance was of a high order, and in some respects exceptionally high. OTA found that ProPAC's resources are adequate and neces- sary for its current functions. The report noted several areas for future consideration, including the intended breadth of ProPAC's responsibility and the emphasis to be placed on assessing specific drugs, medical devices, and medical and surgical procedures. See OTA (1985) for full findings. A discussion of the substance and content of the April 1985 ProPAC report and the re- sponses stemming from it is to be addressed in an OTA report to be delivered to Congress in late 1985. That report also is to cover Pro- PAC's comments on the DHHS secretary's FY 1986 PPS regulations. ProPAC is subject to periodic audit by the General Accounting Office. Much has been speculated regarding the impact of the Medicare prospective payment system. Its major effect will be to shift a vari- ety of hospital incentives. Implementation of PPS will certainly affect overall health ex- penditures, perhaps in the tens of billions of dollars, and will probably mean significant shifting of health care resources via changing case-mix and utilization of technologies. The extent to which ProPAC, an advisory but not a policy-setting group, affects the system re- mains to be seen. The impact of ProPAC will depend on the extent to which the secretary of DHHS and Congress accept the commission's recommen- dations and use in policymaking the data and information generated by the commission. Recent actions of Congress and the adminis- tration to alter the 1983 Social Security Act's provisions for hospital market basket in- creases and the lowering of the discretionary adjustment factor from 1 to 0.25 percent- suggest that the net effect of ProPAC recom- mendations regarding DRG adjustments will be subject to congressional and administra- tion moves. ProPAC's evaluation of the pro- spective payment system may be considered carefully by Congress, or it may be superflu- ous to other congressional action on the pro- gram. As noted earlier, DRG lag may affect dif- fusion of expensive technologies, and Pro-

APPENDIX A: PROFILES PAC decisions regarding the assimilation of technologies into DRGs may affect their dif- fusion and pricing. Such developments would likely depend on many factors, includ- ing the time between DRG reclassifications. Reassessment ProPAC would reassess a technology based on new developments regarding its relative importance in hospital inpatient reimburse- ment. Funding/Budget ProPAC is funded through congressional appropriations. A total of 85 percent of the commission's appropriations comes from the Federal Hospital Insurance Trust Fund, and 15 percent comes from the Federal Supple- mentary Medical Insurance Trust Fund. Congress appropriated $1.5 million for Pro- PAC in FY 1984, but less than one-third of that amount was spent because the commis- sion was in operation for less than the full year. Thus, about $1.05 million was carried over and added to a FY 1985 $2.4 million ap- propriation, for an estimated FY 1985 budget of $3.1 million, plus a FY 1986 carry-over of $0.35 million. A budget of approximately $3.2 million was requested for FY 1986. Example The following pages include the executive summary only of the ProPAC Report and Recommendations to the Secretary, U. S. De- partment of Health and Human Services, April 1, 1985. The full report and accompa- nying technical appendixes are available from ProPAC and the U. S. Government Printing Office. 443 Sources Anderson, G., and E. Steinberg. 1984. To buy or not to buy: Technology acquisition under prospective payment. New England Journal of Medicine 311: 182- 185. Congressional Record. 1983. Social Security Act Amendments of 1983: Title VI—Prospective Pay- ments for Medicare Inpatient Hospital Services. H.R. 1900:H1749-H1756. Hospitals. 1984. 'An honest broker' for fine-tuning Medicare. 58~19~:102-105. Moore, J., Prospective Payment Assessment Com- mission. 1985. Personal communications. Omenn, G. S., and D. A. Conrad. 1984. Implica- tions of DRGs for clinicians. New England Journal of Medicine 311: 1314-1317. Office of Technology Assessment. 1985. First Re- port on the Prospective Payment Assessment Commis- sion (ProPAC) . Washington, D. C. Prospective Payment Assessment Commission. Un- dated. Fact Sheet. Washington, D. C. Prospective Payment Assessment Commission. 1985. Report and Recommendations to the Secretary, U.S. Department of Health and Human Services, April 1, 1985. Washington, D.C.: U.S. Government Printing Office. Prospective Payment Assessment Commission. 1985. Technical Appendixes to the Report and Rec- ommendations to the Secretary, U.S. Department of Health and Human Services, April 1, 1985. Washing- ton, D.C.: U.S. Government Printing Office. Prospective Payment Assessment Commission. 1985. A Report on the Appropriateness of Medicare Hospital Payments for Pacemaker Implantation. Pre- sented to the Committee on Finance, U.S. Senate, and the Committee on Ways and Means, U.S. House of Representatives. March 1. Washington Report on Medicine & Health. March 28, 1983. Congress Begins Prospective Payment Ex- periment. Washington, D.C. Washington Report on Medicine & Health. Janu- ary 7, 1985. DRGs and Quality of Care. Washington, D.C. Young, D. A. 1984. Prospective Payment Assess- ment Commission: Mandate, structure, and relation- ships. Nursing Economics 2:309-311. Young, D. A. 1984. Testimony before the Senate Committee on Labor & Human Services. June 6.

444 ASSESSING MEDICAL TECHNOLOGY PROSPECTIVE PAYMENT ASSESSMENT COMMISSION REPORT AND RECOMMENDATIONS TO THE SECRETARY U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES APRIL 1, 1985 - ProPAC-

APPENDIX A: PROFILES 445 Executive Summary In 1983 Congress enacted the most far reaching changes in the Medicare program since its estab- lishment in 1965. Left behind was a cost reim- bursement system that by general agreement had produced unacceptable hospital cost inflation. Congress mandated that the inpatient hospital care rendered Medicare beneficiaries would hence- forth be paid on the basis of a prospective pay- ment per case, using diagnosis-related groups (DRGs) to classify and label the hospital product being purchased. This report is the product of the congression- ally-established Prospective Payment Assessment Commission, fifteen individuals knowledgeable about the health industry who were vested with the responsibility of analyzing the new prospec- tive payment system (PPS) and advising the Sec- retary of the Department of Health and Human Services and the Congress on ways of improving it. The recommendations emanate from a pro- found concern that the fundamental changes in- troduced October 1, 1983 be implemented in as fair, cost-effective, and quality-enhancing a man- ner as possible. The Commission, which began meeting in De- cember 1983, has focused its attention on two ma- jor questions: 1. By what percentage should Medicare's pay- ments for hospital discharges in fiscal year 1986 increase or decrease (the "Update Factory? 2. What changes, if any, should be made con- cerning payments to hospitals for specific treatments or procedures by the Medicare program (adjustments of DRG classifications and weights)? The body of this report and accompanying technical appendixes explain the Commission's ac- tions and decisions in substantial and technical detail. For purposes of this summary, six major points should be emphasized: · The Commission's unanimous recommenda- tions reflect five major priorities: maintain- ing access to high-quality health care; en- couraging hospital productivity and long- term cost-effectiveness; facilitating innova- . . lion and appropriate technological change; maintaining stability for providers, consum- ers, and other payers; and basing decisions upon reliable and timely data and infor- mation. The Commission recommends that next year's Medicare hospital payments incor- porate inflation in hospital input prices and higher costs due to treating sicker patients, minus one percentage point. This recommen- dation would result in payment increases sig- nificantly less than those of recent years. The inflation minus one percentage point repre- sents the Commission's best judgment as to the net change in payments needed to pro- vide scientific and technological advances in the hospital industry, balanced by changes in hospital productivity and in the hospital product. In particular, the Commission's cal- culations reflect a judgment and belief that appropriate, sustained, and necessary tech- nological growth in the health care industry can be achieved in part by savings generated through improvements in hospital produc- tivity. The Commission recommends action on two problems arising from PPS implementation. Specifically, the Commission urges the Sec- retary of the Department of Health and Human Services to move quickly to improve the current definition of hospital labor mar- ket areas, in order to better adjust PPS rates for area wage differences. The Commission also urges the Secretary to institute adjust- ments for hospitals that incur higher Medi- care costs per case associated with treating a greater proportion of low income patients ("disproportionate share hospitals". · For fiscal year 1986, the Commission recom- mends adjusting all of the DRG weights using newer, more complete, and more accurate data. Such adjustment or "recalibration" is intended to enable PPS to reflect changes in hospital practice during recent years. As part of the recalibration process, the weights should also be adjusted to avoid building changes in coding practice into future PPS

446 payments. The Commission's recommenda- tions incorporate its review of a number of specific medical practices and technologies. Additional data collection and analysis re- garding other such practices and technologies are required in order to reach well-informed conclusions. · While making no recommendation at this time on the pace of transition to national payment rates, the Commission is aware of concerns that have arisen regarding the im- pact of that transition on different hospitals and regions. The transition issue involves weighing the desirability of continued imple- mentation of a system already clearly yield- ing positive results, against the possible harms of delaying that transition to correct PPS inequities and shortcomings. The Com- mission will continue to analyze this impor- tant issue. · The Commission offers its analysis and rec- ommendations in an environment of debate concerning future directions in health care de- ASSESSING MEDICAL TECHNOLOGY livery and financing. The recommendations themselves are predicated on continued im- plementation of the current PPS system. They seek to address as sensibly as possible the tension among several compelling and competing considerations: Federal budgetary constraints; maintenance of Medicare bene- ficiaries' access to high-quality care; and changes in the hospital industry. Should any health policy proposals affecting PPS be adopted, the Commission will respond with appropriate analytical work. The report that follows is by design and neces- sity a technical document. The Commission issu- ing it, however, remains mindful of the fact that the report's analysis, discussion, and recommen- dations will directly affect millions of Medicare beneficiaries- individuals for whom the pluses and minuses of the "Update Factor" will translate into a significant impact on the kind of life-giving treatment they receive. OVERVIEW OF THE COMMISSION'S RECOMMENDATIONS The Commission's 21 recommendations fall into two major categories: recommendations re- garding the update factor and recommendations regarding adjustments of DRG classifications and weights. The first 16 recommendations address the up- date factor. In recommendation 1, the Commis- sion proposes updating the standardized amount by the projected increase in the hospital market basket, minus one percentage point, plus an allowance for the estimated increase in real case- mix complexity during fiscal year 1985. Several of the first 16 recommendations involve specific market basket issues, including the desirable num- ber of such market baskets, wage components, and correction of forecast errors. Recommendations 13 through 15 address dis- tributional concerns. The Commission selected the definition of hospital labor market areas and disproportionate share hospitals as two problem areas of PPS deserving immediate attention in the establishment of the fiscal year 1986 payment rates. This does not imply that other problem areas are not also of great importance, but the Commission believes that the distributional con- sequences of these two problems are sufficiently severe, and the potential for finding workable solutions is sufficiently high, that immediate at- tention is warranted. Recommendation 17 recommends recalibration of the DRG weights with a data base that is newer, more complete, and more accurate than the 1981 data used to create the current DRG weights. The Commission's recommendation reflects its belief that, because of potential inaccuracies in the data originally used to establish the DRG weights and changes in hospital practice patterns since 1981, a full recalibration for the 1986 rates is advisable. Recommendations 18 through 20 pertain to spe- cific DRG weight, classification, and assignment issues concerning three procedures: pacemaker implantation; cataract extraction and intraocular

APPENDIX A: PROFILES lens implantation; and percutaneous transluminal coronary angioplasty. Recommendation 21 con- cludes that two additional procedures, bone mar- row transplantation and treatment of infective en- docarditis, do not require in-depth analysis at this time. THE COMMISSION'S FUTURE AGENDA While much has been accomplished during the Commission's first year, many important PPS- related issues require further evaluation. The Commission looks forward to analyzing a vari- ety of complex matters including: · The measurement of case mix used for PPS and evaluation of alternative case-mix systems. · Improvement in the methods used to account for resources consumed during specific types of hospital stays. Special emphasis will be placed on analyzing the allocation of nurs- ing costs to DRGs. PPS payment policies, with emphasis on ad- justments for differing costs of hospitals serv- ing large numbers of low income patients, definitions of hospital market areas, and ef- fects of the transition to national payment rates. . 447 The Commission will make future recommen- dations concerning these and many other DRG weight, classification, and assignment issues, as new information becomes available. · System responsiveness to changes in practice patterns, focusing on payment mechanisms for new or changing technologies. In addi- tion, a number of specific diagnostic and therapeutic practices are currently being ex- amined: Cyclosporine used in renal transplantation - Magnetic resonance imaging Dual joint procedures in one hospitali- zation Treatment for alcohol dependence Cochlear implants —Extracorporeal shock wave lithotripsy Dermatologic disorders · The effects of PPS on health care delivery, such as changes in quality of care and health outcomes, changes in types of patients treated in hospitals, changes in the hospital product, and regional practice pattern vari- ations. STRUCTURE OF THE REPORT AND APPENDIXES The Commission's report consists of two vol- umes. In this volume, the Commission's first chapter presents background information con- cerning establishment of the prospective payment system. Chapter 2 identifies the major priorities and approaches underlying the Commission's recommendations. The recommendations them- selves, along with explanatory material, appear in Chapter 3. The fourth and final chapter of the first volume explores areas and issues requiring substantial Commission attention in the year and years to come. In developing its recommendations the Com- mission considered staff analyses and the views of numerous technical experts. The purpose of volume 2—the Technical Appendixes is to pre- sent much of this background material to afford greater insight into the Commission's decisions. The appendixes consist of both descriptive and analytical pieces covering the origins of the pro- spective payment system, the determination of prospective payments, the update factor, and DRG recalibration. They underscore many of the dilemmas and issues confronting the Commission during its deliberations.

448 LIST OF RECOMMENDATIONS The Update Factor Recommendation 1: Amount of the Update Factor For fiscal year 1986, the standardized amounts should be updated by the projected increase in the hospital market basket, minus one percent- age point, plus an allowance for the estimated increase in real case-mix complexity during fiscal year 1985. The negative one percentage point is a combined adjustment of a positive allowance for scientific and technological advancement and a negative allowance for productivity improve- ment and hospital product change. This recommendation reflects the Commis- sion's collective judgment of the appropriate increase in the level of payment per Medicare discharge under PPS, assuming that the Com- mission's other concerns regarding the market basket component of the update factor, the DRG weighting factors, and the distribution of pay- ments across PPS hospitals are also addressed in the fiscal year 1986 payment rates. Further, this recommendation is based on the premise that no net reductions or increases in average per case payments to hospitals will be effected through measures other than the update factor, such as reducing the indirect teaching adjustment, incor- porating capital payment under PPS at a budget- saving level, adjusting for coding changes occur- ring before fiscal year 1985, or any other changes in total payments per discharge under PPS. The Hospital Market Basket Recommendation 2: The Number of Market Baskets For fiscal year 1986, a single market basket should be continued for those hospitals under PPS. The Commission will undertake a study to determine the appropriateness of developing market basket measures that reflect variation in economic factors across hospitals. The use of multiple market baskets by region and classes of hospitals within regions will be examined. If the analysis indicates that multiple market baskets are appropriate, the study will also include an assessment of the data required for implemen- tation. ASSESSING MEDICAL TECHNOLOGY Recommendation 3: Market Basket for Psychiatric, Rehabilitation, and Long-Term Care Hospitals Separate market basket weights should be used for the group of psychiatric, rehabilitation, and long-term care hospitals and related distinct-part units that are exempt from PPS, but subject to the TEFRA rate of increase limitation. Separate market basket weights need not be developed for children's hospitals. Recommendation 4: Market Basket Wage Component Occupational Groups The wage component of the market basket should be split into three categories, each with separate weights: Managers and Administrators, Professionals and Technicians, and Other Hos- pital Workers. Changes in wages for these cate- gories should be measured as follows: · Managers and Administrators: the Employ- ment Cost Index (ECI) for Managers and Ad- ministrators. · Professionals and Technicians: a 5~50 blend of the Average Hourly Earnings (AHE) for the hospital industry and the ECI for Pro- fessionals and Technicians. · Other Hospital Workers: a 50-50 blend of the AHE for the hospital industry and the ECI for all private industry. Recommendation 5: Employment Cost Index Feasibility Study For the long run, the Secretary should work with the Bureau of Labor Statistics to study the advantages and feasibility of developing an Em- ployment Cost Index for the hospital industry that includes both public and private hospitals and covers increases in both wages and fringe benefits. Recommendation 6: Study Effects of Changes in the Minimum Wage Law on Hospital Workers The Commission plans to study the extent to which hospital workers would be affected by changes in the Federal minimum wage law. The intent of the study is to detect whether, under PPS, workers who earn more than the minimum

APPENDIX A: PROFILES wage are differentially affected by statutory in- creases in the minimum wage compared with workers in other industries. If a differential ef- fect is found to exist, the Commission will con- sider requesting the Secretary to take appropri- ate action. Recommendation 7: Correction of Market Basket Forecast Errors The update factor should include a correction for substantial errors made in the previous year's forecast of changes in the external price meas- ures used in the hospital market basket. In the judgment of the Commission, substantial errors are those that equal or exceed 0.25 percentage points (or, when rounded in the published fore- casts, 0.3 percentage points). The Commission will undertake a study to determine the extent to which differences between forecasted and ac- tual increases in the internal price change meas- ures are due to factors beyond the hospitals' con- trol. Substantial errors determined after study to be due to factors beyond the hospitals' control should be corrected in the update factor. Recommendation 8: Statutory Change for Forecast Error Correction The Secretary has determined that she does not have the statutory authority to correct for Recommendation 13: Improvement of Labor market basket forecast errors. Therefore, the Sec- Market Area Definitions retary should seek statutory change to provide explicitly that the update factor include a cor- rection for errors in forecasting the market bas- ket beginning in fiscal year 1986. Recommendation 9: Rebasing of Market Basket Weights Market basket weights should be rebased at least every five years. Rebasing should be per- formed more frequently if significant changes in the weights occur. In addition, the market bas- ket weights will need to be rebased if payment for capital or direct medical education is included in the PPS rates. 449 productivity improvement, and hospital prod- uct change should be set at minus one percent- age point. Recommendation 11: Adjustment for Case-Mix Change Prospective payments to individual hospitals and in the aggregate should reflect real changes in case mix. Changes in reported case mix that are unrelated to actual differences in the types of patients treated should not be built into future PPS payments. Recommendation 12: Update Factor for Exempt Hospitals In addition to the projected increase in the market basket, hospitals and hospital distinct- part units exempt from PPS should receive a minus one percentage point adjustment in their fiscal year 1986 update factor for productivity improvement and scientific and technological ad- vancement. Hospital Labor Market Areas Area Wage Index Discretionary Adjustment Factor Recommendation 10: Allowance for Productivity and Scientific and Technological Advancement Goals For the fiscal year 1986 payment rates, the allowance in the discretionary adjustment fac- tor for scientific and technological advancement, In order to better reflect hospital labor mar- kets, the Secretary should improve, as soon as possible, the current definition of a hospital la- bor market area used to adjust PPS rates for area wage differences, taking into account variations in wages paid in the inner city compared with suburban areas within a metropolitan area, and variations paid in different rural locations within a state. Implementation of this recommendation should not result in any change in aggregate payments. Disproportionate Share Hospitals Recommendation 14: Disproportionate Share Adjustment for Fiscal Year 1986 The Secretary should develop a methodology for adjusting PPS rates for disproportionate share hospitals and implement the adjustment in fiscal year 1986. The adjustment should be im- plemented so that it does not change aggregate payments.

450 ASSESSING MEDICAL TECHNOLOGY Recommendation 15: Definition of Disproportionate Share Hospitals The Secretary should complete the develop- ment of a definition of disproportionate share hospitals in ample time to include adjustments for these hospitals in the fiscal year 1986 PPS payment rates. The Secretary should consider broader definitions of low income than simply the percentage of patients who are Medicaid re- cipients and should determine whether the share of Medicare Part A patients should be excluded from the definition. Rebasing the Standardized Amounts Recommendation 16: Rebasing the Standardized Amounts The standardized amounts used to determine hospital payments under PPS should be recal- culated using cost data that reflect hospital behavior under PPS. The results of such a recal- culation, with appropriate modifications, could be used to rebase the standardized amounts. Al- though recent cost data are not available to recalculate the standardized amounts for the fiscal year 1986 payment rates, the Secretary should implement a process for timely collection of the cost data necessary for future recalcula- tion. The Commission will later consider more specific recommendations regarding the timing, data sources, and process for rebasing the stand- ardized amounts. DRG Classifications and Relative Weighting Factors Recommendation 17: Recalibrating the DRG Weights For fiscal year 1986, all DRG weights should be recalibrated using the 1984 PAT]3ILL data set. The newly recalibrated weights should be: (1) Normalized so that the average case weight is the same as it was at the beginning of fiscal year 1985, thereby incorporating DRG weight adjustments made before the start of fiscal year 1985 (2) Adjusted for any demonstrable changes in reported case mix occurring during fiscal year 1985 Recommendation 18: Cardiac Pacemaker Implantation The DRGs involving cardiac pacemakers, DRGs 115, 116, 117, and 118, should be recali- brated in the same manner as other DRGs to re- flect changes in practice since 1981. The Com- mission will continue to analyze diagnosis and procedure coding and DRG classification related to pacemaker implantation and replacement; the distribution of costs and payments across dis- charges, hospitals, and DRGs; and the impact of PPS on the quality of patient care. Recommendation 19: Cataract Extraction and Intraocular Lens Implantation DRG 39, Lens Procedures, should be recali- brated in the same manner as other DRGs to re- flect changes in practice since 1981, including the more frequent implantation of an intraocular lens following cataract removal. The Commission will continue to monitor resource use in this DRG to determine whether the types of patients treated as hospital inpatients change with in- creased outpatient surgery for cataract removal. Recommendation 20: Percutaneous Transluminal Coronary Angioplasty Cases in which Percutaneous Transluminal Coronary Angioplasty (PTCA) is the principal procedure should be removed from DRG 108 and temporarily assigned to DRG 112 before recali- bration. The Secretary should immediately im- plement a mechanism to identify bills for cases in which PTCA is performed in order to provide data for analysis and additional adjustments as appropriate. Recommendation 21: No Change Recommended for Bone Marrow Transplantation and Infective Endocarditis The Commission has examined Bone Marrow Transplantation and Treatment for Infective En- docarditis and is recommending no changes in DRG classification or weights at this time, other than those that would occur with recalibration. Inflation will continue to be gathered and the subjects reconsidered at an appropriate time.

Cost Benefit Studies Program Smith Kline & French Laboratories 1900 Market Street P.O. Box 7929, Suite #410 Philadelphia, PA 19101 (215) 751 4000 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ E ffectiveness Cost-Benefit X _ ~ Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded A pplication of Technologies Prevention Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing X* Clinical trials X* Epidemiological and other observational methods X Cost analyses Simulation/modeling Group judgment Expert opinion Literature syntheses Approximate 1985 budget for technology assessment: $550,000t * SK&F-CBS may piggyback'? cost studies on clinical trials and epidemiologi- cal studies conducted by SK&F for establishing safety and efficacy of drugs. t This amount is the estimated budget of the SK&F-CBS Program only. The SmithKline Beckman Corporation spent nearly $300 million on research and de- velopment in 1984, or over 9 percent of total sales. SMITH KLINE & FRENCH COST-BENEFIT STUDIES Introduction In order to place the Smith Kline & French Cost-Benefit Studies (SK&F-CBS) program in proper context of the company's drug as- sessment activities, this introduction begins 45 with an overview of Smith Kline & French Laboratories. Smith Kline & French Laboratories (SK&F) is the pharmaceutical division of SmithKline Beckman Corporation. Its main business is the research, development, and marketing of prescription pharmaceutical products. SmithKline Beckman's total assets

452 as of December 31, 1984, were $3.2 billion. Its major product areas are ethical pharma- ceuticals (52 percent contribution to 1984 revenues), instruments and chemistries (20 percent), clinical laboratory (8 percent), eye and skin care (8 percent), consumer health care (5 percent), and animal health care (7 percent) . SK&F markets its products worldwide. A major share of SK&F sales, particularly of SK&F's leading product, the antiulcer drug Tagamet (active ingredient, cimetidine), comes from overseas markets. SK&F markets 24 brand-name prescrip- tion pharmaceutical products in the United States. Worldwide sales in 1984 were approx- imately $1.5 billion. Tagamet is the world's largest-selling drug, with worldwide sales in 1984 of approximately $900 million and U.S. sales of about $450 million. Tagamet ac- counted for 30 percent of all sales for the SmithKline Beckman Corporation, and 60 percent of its prescription pharmaceutical sales (SmithKline Beckman, 19844. SK&F's second leading product is the diuretic Dyazide (active ingredients, hydroch- lorothiazide and triamterene) introduced in 1965. Dyazide is the major product of SK&F's cardiovascular products group, which had $304 million in 1984 sales. In the 1984 U. S. retail sales market, Tagamet ranked first and Dyazide third among all pre- scription drugs. SK&F's third major product area is antibi- otics, with three cephalosporin products. Other major products are the tranquilizer Thorazine (active ingredient chlorproma- zine) developed in the mid-1950s, and cough- cold products. As of the end of 1984, SK&F was awaiting approval from the Food and Drug Administration (FDA) to market an oral gold antiarthritic compound, Ridaura (active ingredient, auranofin). SK&F's assessment activities involve the full range of research and development and testing required for prescription drugs. This includes synthesis of new chemical entities, testing in animals, and establishing evidence of safety and efficacy in humans. The com- pany has a pharmaceutical research staff of 1,800. Evidence of safety and efficacy (the characteristics or the effect of the drug when ASSESSING MEDICAL TECHNOLOGY used under ideal conditions) in humans is normally developed through randomized, double-blind clinical trials. The findings of such trials usually cite the effects that the drug has, compared to placebos and/or stan- dard treatments, on various biological end points for appropriate levels of statistical sig- nificance and confidence intervals. For ex- ample, measured end points of efficacy for ci- metidine include healing of the ulcer, concomitant use of antacids, side effects, and relief of other symptoms. For the rheumatoid arthritis drug auranofin, measured end points include the number of swollen or ten- der joints, the time to onset of fatigue in the morning, the number of seconds taken to walk 50 feet, and various chemical determi- nations. In addition to the clinical trials used for es- tablishing evidence for safety and efficacy, other data are gathered in nonrandomized studies using surveillance and other epidemi- ological methods before and after introduc- tion of the drug into the market. These so- called phase IV studies provide longer-range, experiential information about drug safety and efficacy which may not be evident from premarketing, double-blind clinical trials alone. Typically, a thousand or more patients may be studied in one form or another before marketing, and several thousand may be studied after the drug is on the market. See Chapter 4 for further discussion of technol- ogy assessment in the drug industry. The SK&F Cost-Benefit Studies effort (SK&F-CBS) was initiated in 1977 as a result of the developing marketing experience with cimetidine, which had been introduced in overseas markets in 1976 and in the United States in 1977. Immediately following its in- troduction, the worldwide sales of cimetidine increased much faster than had been fore- cast. Although cimetidine was in great de- mand by physicians and patients, its price at the time (about $1.20 per day to the patient) was considerably higher than that of older drugs used in the treatment of duodenal ul- cer, such as anticholinergic agents (about $0.38 per day) and antacids (about $0.50 per day). The price of cimetidine was set to be comparable with that of recent drug innova- tions in other disease areas and to reflect the

APPENDIX A: PROFILES 10 years of gastrointestinal and related R&D preceding the introduction of the drug. Since its introduction, other duodenal ulcer prod- ucts have been marketed at prices compara- ble or exceeding the current price of cimeti- dine (e.g., ranitidine at $1.45 per day). SK&F-CBS was introduced to document, in addition to its medical advantages, the cost advantages of cimetidine to physicians, third-party payers, and health services pro- grams (e.g., national health services, state Medicaid programs, commercial insurance companies, health maintenance organiza- tions tHMOs]) in an environment of increas- ing cost-containment and price justification pressures. The decisions of these parties to prescribe, purchase, and pay for cimetidine affect the demand for the drug for large groups of patients. (In certain countries, in- troductory prices and rates of reimbursement and price increases must be negotiated.) In a broader sense, cimetidine appeared to offer an excellent opportunity for demonstrating the economic contributions to society of ma- jor new pharmaceutical products. Purpose The purpose of SK&F-CBS is to document the cost-benefit and cost-effectiveness of SK&F's major prescription pharmaceutical products. This is done in addition to the bio- logical/medical evaluations which are con- ducted at SK&F. SK&F-CBS principally ad- dresses the implications of cost considerations on potential limitations of use of and reim- bursement for SK&F prescription pharma- ceuticals. It is also intended that the program document the value of pharmaceuticals in general, and SK&F products in particular. Subjects of Assessment The subjects of assessment are chemical entities anticipated to be marketed as pre- scription drugs. In 1984, the antiarthritic drug auranofin and the antibiotics cefonicid and ceftizoxime were the primary subjects of SK&F-CBS studies. Other SmithKline Beck- man companies conduct assessments of diag- nostic and bioanalytic instruments and ser- vices, and animal, eye care, and consumer 453 (over-the-counter) drug and health care products. Stage of Diffusion The drugs assessed are those being brought onto the market, including those awaiting approval by the FDA. The program does not routinely study products put on the market prior to 1977-1978, when the program was initiated. Concerns The particular concerns of SK&F-CBS in- clude market price, cost-benefit, cost-effec- tiveness, and quality-of-life, in addition to SK&F's traditional assessment concerns of safety and efficacy. Requests Candidates for assessment are the new chemical entities developed by SK&F. As is typical for a firm in the prescription drug in- dustry, only one or two major products may be introduced in any one year. Selection If a product in research and development meets expectations in clinical trials for safety and efficacy and promises to be marketed, it becomes a subject for SK&F-CBS evaluation. Process SK&F-CBS cost-benefit and cost-effective- ness evaluations for any one product may in- volve several types of analyses. SK&F con- tracts with academic research institutes and other agencies to conduct studies and data analyses; data are used from published sources (e. g., medical/epidemiological litera- ture, National Center for Health Statistics, and other national data); data may be pur- chased by SK&F from other sources; and SK&F-CBS conducts its own analyses. The SK&F-CBS managers and the SK&F product management staff jointly develop an evaluation plan. Consultation is sought from SK&F and outside clinical personnel as ap-

454 propriate, such as cases in which cost-benefit evaluations involving clinical trials are to be conducted. Types of studies that are conducted for the cost-benefit and/or cost-effectiveness evalua- tion of a drug may include the following: · cost of disease determinations using sur- veys and other data sources; · economic/cost inquiries in premarketing randomized clinical trials; · expert estimates of treatment costs with and without a drug; · postmarketing epidemiological studies (e.g., time-series studies of populations be- fore and after using a drug, and cross-sec- tional comparisons of patients undergoing treatment with and without the drug); · quality-of-life studies using patient questionnaires; and · decision-tree analyses of alternative treatments. Results of randomized clinical trials con- ducted and sponsored by SK&F for investi- gating drug safety and efficacy are also used as appropriate. Assessors Although these studies are usually spon- sored by SK&F, they are generally conducted by persons outside the organization. As is evi- dent from the various study types, the asses- sors include a diverse range of personnel, both from within SK&F and from outside or- ganizations, often research institutes with ac- ademic ties. These include research design personnel, epidemiologists, economists, and physicians and other health care personnel. Turnaround Turnaround varies according to study type. It may vary from 2 months for decision- tree analyses using existing cost data, to 2 or 3 years for studies involving clinical trials, to 5 years or more for longitudinal studies. It has been the experience of SK&F that 10 to 12 years on average are required from synthesis and testing of new chemical entities through FDA approval of a prescription drug. ASSESSING MEDICAL TECHNOLOGY Reporting The outside, independent investigators who conduct SK&F-sponsored studies are free to publish their findings. These are usu- ally published in the appropriate medical and other literature. Prepublication drafts of SK&F-sponsored research are sometimes cir- culated to appropriate SK&F personnel. Since 1977-1978, when the SK&F-CBS pro- gram began with cimetidine, approximately 20 papers and reports have been published on cimetidine studies conducted and/or spon- sored by SK&F. Publication sources have in- cluded such journals as Lancet, the Journal of Clinical Gastroenterology, and Social Sci- ence and Medicine; publications of the Con- gressional Office of Technology Assessment (OTA), the Stanford Research Institute, and Robinson Associates (Bryn Mawr, Pa.~; and a number of foreign publications and interna- tional conference proceedings. Study results may be distributed to physi- cians and others with special interests in the particular area of research. Quality-of-life study findings may be provided to physicians to assist them in weighing efficacy and side effects of drugs in prescribing decisions. The SK&F corporate affairs and marketing de- partments send reports to leaders in the pri- vate and public sectors, such as professional health economists and Medicaid program ad- ministrators, to provide economic perspec- tives regarding the reimbursement of SK&F prescription drugs. Impact SK&F-CBS findings are intended to have an impact particularly on commercial and government third-party payers, and on do- mestic and foreign government agencies charged with the regulatory approval of drugs, introductory pricing of drugs (e.g., in Japan), reimbursement of drugs at particular rates (e.g., in France), and allowing price in- creases. Specific impacts are hard to deter- mine; however, SK&F attributes the addi- tion and retention of cimetidine on the formularies of several Medicaid jurisdictions to evidence of the effectiveness of cimetidine in reducing ulcer surgery and patient treat-

APPENDIX A: PROFILES ment costs. It is likely that the original pric- ing and/or reimbursement status of cimeti- dine in various countries overseas was at least partly dependent on studies of its cost-effec- tiveness, according to SK&F. Reassessment SK&F-CBS has not yet conducted reassess- ments. However, the introduction of com- petitive drugs may prompt reassessment in which SK&F-CBS would seek to supply new comparative cost-benefit and cost-effective- ness evidence. SK&F has traditionally con- ducted clinical reassessments for newly re- ported side effects or indications of a drug. Funding/Budget Though varying within a wide range, the annual budget for SK&F-CBS has averaged about $700,000. The estimated 1985 budget for the program is $550,000. Funds have been allotted from SmithKline Beckman and from various SK&F departments such as state government affairs, product management, and medical affairs. Studies range in cost from $5,000 for small desk-top analyses to over $1 million for certain clinical and time- series studies. 455 Example On the following pages is an article de- scribing approaches used in SK&F-CBS and an overview of such studies of cimetidine. The article was published in Managerial and Decision Economics, 4~1) :50-62, 1983, and is reproduced here with permission. Sources Kleinfield, N. R. May 29, 1984. SmithKline: One- drug image. New York Times. D1. Koenig, R. December 23, 1983. SmithKline's Beck- man unit off to slow start. Wall Street Journal. Neuhauser, D. 1982. New drug evaluation: Ci- metidine. Medical Care 20:755-757. Office of Technology Assessment. 1981. The Impli- cations of Cost-Effectiveness Analysis of Medical Technology. Washington, D.C.: U.S. Government Printing Office. Paterson, M. L. 1983a. Cost-Benefit Evaluation of a New Technology for Treatment of Peptic Ulcer Dis- ease. Managerial and Decision Economics 4:50-62. Paterson, M. L. 1983b. Measuring the socio-eco- nomic benefits of auranofin. In G. T. Smith (ed.), Measuring the Social Benefits of Medicine. London: Office of Health Economics. Paterson, M. L., Manager, Cost-Benefit Studies, Smith Kline & French Laboratories. 1985. Personal communication. SmithKline Beckman. 1984. Annual Report 1983. Philadelphia. Standard & Poor's Corporation. 1983. Industry Surveys, Health Care: Basic Analysis 151 :H13-H35.

456 ASSESSING MEDICAL TECHNOLOGY Cost-Benefit Evaluation of a New Technology for Treatment of Peptic Dicer Disease MORTON L. PATERSON Smith Kline & French Laboratories, Philadelphia, USA Psychosocial benefit resists monetary expression. However, reduction in costs, with no loss of benefits assumed, improves a cost-benefit ratio. The effect of cimetidine on the costs of ulcer has been widely studied. Randomized clinical trials show reductions in surgery and work loss among cimetidine-treated patients versus placebo controls. In the community, time series studies have documented drops in ulcer surgery, averaging about 25% below the expected trend line, following marketing introduction of the drug. These, plus a cross-sectional study of Medicaid patients with and without use of cimetidine, indicate that the drug has reduced the net direct costs of ulcer disease. INTRODUCTION Smith Kline & French's new drug product for ulcer disease, cimetidine, was forecast in 1977 to achieve a substantial sales volume. The forecast was made just as pressures were increasing to contain the fast-rising costs of health care. Since then the drug has become conspicuous as both an unusually efficacious new technology and as a leading, if not the leading, item on many pharmaceutical reim- bursement budgets around the world. Cost-benefit matters regarding cimetidine have become impor- tant indeed. Do the benefits of cimetidine in the community exceed its costs? This is an economic question, testing whether the cimetidine undertak- ing - its research and development, widespread adoption and effect on society - has in the broadest sense been worthwhile. COST-BENEFIT ANALYSIS There are objectors to cost-benefit questions of this kind. Some might like to let a free marketplace answer the question: consumers will pay for a drug what it is worth to them. Imperfectly informed consumers and the physician's role as product prescriber are not typical of a free market; nor is patent protection, and certainly not reimbursement of costs by third parties so, the free market objector is probably a straw man. However, he makes the point that cost-benefit analysis is a substitute for market forces. In fact, it began with evaluation of public works: Should a dam be built, an airport? More recently, the cost-effectiveness of different national defense systems has been evaluated: Which gives more Bang for the buck'? Put crudely, a national concern today is more 'health for the buck'. This leads to a different objector to cost-benefit analysis in health. Hippocratic in spirit, he or she must be taken quite seriously. In fact, it is this person most of us want for our physician. He says, in effect, let us do everything medically possible for the patient. The economist will tell him that is not possible; society has other goals; resources are not infinite. Yet the physician feels it unethical, if not impossible' to deny a particular patient a treatment or test on the basis of predicted other patients who may need it instead. Usually. in the end, someone other than the physician sets the dollar limit and probably the rationing rules. Economic, not just medical, evaluation becomes necessary. When examining the benefits and costs of cimetidine the following equation was used as a model: Present value of an investment over time: where: CCC-O ~ 43 - S70/83/0004-0050$06.50 V hi, (B'-C,) ', (I+r) V = value = sum of years t, + t2 + etc. B = benefits C = costs r = rate of discount ~)Wiley Heyden Ltd. 1983

APPENDIX A: PROFILES The symbols indicate that the value of an invest- Reducing costs: ment over time is the benefits in a given year, t, minus the cost in that year, with the difference discounted at a rate, r, reflecting the value of money over time. That means that all the years over the lifetime of the investment must be considered. Since most of what follows concerns only one year at a time, we can simplify the equation in the following manner: Value when all benefits and costs occur in same year: V = B - C where: V= value B = benefits C = costs Value equals benefits minus costs during one year. The important point this brings out is that we cannot fill in B in the equation! We know that cimetidine inhibits the secretion of gastric acid, heals ulcers, relieves gastrointestinal pain and distress, reduces the need for concomitant antacids and forestalls ulcer surgery. This has been proven in clinical trials. We have heard of and talked to people who could eat normally, sleep all night, work more regularly and enjoy family life again because of cimetidine. But we have not quantified these changes in quality of life - not most of them - and certainly have no single number for B to put in the equation. Moreover, if we did have a number, it would need to be translated into dollars, so that C, the dollar costs, could be subtracted from it. What is the dollar value to patients of pain-free nights, of a pleasant disposition, of not having to swallow antacids, of not getting anesthetized and cut in an operating room? Economists would dearly love to be able to find out. (You can ask patients questions about their willingness to pay to avoid these things. We might have tried that with cimetidine, but it is obviously a very tricky and controversial matter.) Are we thus stymied by the lack of numbers before we start? Not necessarily. What we want is a net gain in benefits from the investment which the payers for health care make in cimetidine. This is shown thus: Gain from an investment comes from raising benefits: V = B—C 10 = 15 - 5 Invest: 12 = 17 - 5 gain = 2 Raising benefits and reducing costs: V = B - C 10 = 15 - 5 Invest: 14 = 17 - 3 gain = 4 457 V = B - C 10 = 15 - 5 Invest: 12 = 15 - 3 gain = 2 This shows at least three ways of producing a gain. The most obvious is to increase the benefit, in the sense of health-related quality of life. Let us use the number 15 to represent the benefit of therapy before or without cimetidine and 5 to represent the cost needed to produce that benefit - the drugs, doctor visits, tests, operations, bed days and so on. The value, V, then equals 10, benefit minus cost. If with cimetidine the benefit is increased to 17, the investment has produced a gain of 2. If with cimetidine the benefit is 17 and the cost drops to 3, the gain is 4. Now, let us assume that cimetidine has no effect on quality of life-that is, produces no new health benefit, even though we know it does - but that cost declines to 3. We still have a net gain of 2. Therein lies the hope of doing a cost-benefit study of cimetidine; because cost reduc- tion is always cost-beneficial, as long as the benefit-the health status-at least holds constant. If cimetidine can pass this cost-reduction test, it is 'home free'. If it does not pass, it may perfectly well still be cost-beneficial because it increases benefits more than costs. Cost reduction is an unfair test, to be undergone by only the hardiest of new technolo- gies - or by the hardiest of cost-benefit analysts. CIMETIDINE AND EPIDEMIOLOGY Our question has now become: What is the effect of cimetidine on the costs of ulcer disease? The first country studied was the Netherlands (Bulthuis et al., 1977). It can be seen from Table 1 that there are two kinds of cost: medical or treatment costs, called direct; and productivity-related costs, called indirect. These are traditional groupings. The major direct cost in 1975 was hospitalization, at Table 1. The Netherlands: Pep- tic Ulcer Costs (in mil- lion dollars) Hospita I ization Surgeon fees Polyclinics Consultations Diag noses Drugs Total direct Absenteeism Disability Mortality Total indirect Total Population 1975 20.8 1.7 1.3 1.4 1.9 0.9 27.8 82.9 82.9 110.7 13 650 000

458 ASSESSING MEDICAL TECHNOLOGY Table 2. United States: Duodenal Ulcer Costs (in million dollars) Hospita ~ ization Surgeon fees Consultations Diagnoses Drugs Nursing home Other Total direct Absenteeism Disability Mortality Total indirect Total Population 1 977 732 74 46 66 85 11 2 1016 455 476 245 1176 2192 215 000 000 $20.8 million. Drugs were a very small share in the Netherlands. Total direct costs were $27.8 million. Indirect costs were much larger, even with only absenteeism considered. Total costs of ulcer disease to the Dutch economy were $110.7 million. Table 2 refers to the United States, and only duodenal ulcer costs, in 1977 (adapted from Chandler and von Haunalter, 1977). About 80% of ulcers in the United States are in the duodenum; the other 205to are in the stomach. In the United States direct costs almost equal indirect costs. Hospitalization is again the major medical cost and a tempting area in which to look for savings. A 12% reduction in hospital costs for example, would more than offset a 1005to increase in drug costs. Similar studies were done in several European countries. As one ranges into the Latin countries of Europe, hospital costs still constitute the largest direct cost, but less so than in the north; and drugs are a larger share than in the north. One value of a cost-of-disease study is that it shows the cost categories which the new technology may increase or decrease. Of course, it is the net cost effect we want to know. In the United States a survey was done in 1977 among the early clinical investigators of cimetidine in duodenal ulcer (Olitsky et al., 1978). They were asked to judge from their experience what the specific treatment and response patterns of duoden- al ulcer patients would be over a year both with and without cimetidine. Their answers were costed out and the results projected to the national level. ~ . 4 Table 3 shows that c~met~d~ne was estimated to reduce hospitalization costs by 22%, raise drug - 2 costs by 25%, reduce indirect costs by 20% and produce a total net saving of 18% - assuming that the drug had been used in 50% of duodenal ulcer patients in 1977. A similar exercise in the Nether- lands produced similar results. These are estima- tions only, needing verification by hard data, but they are useful to show what we mean by a net effect of cimetidine on the cost of ulcer disease. Table 3. United States: Duodenal Ulcer Costs if Cimetidine Used in 50% of Patients (in million dollars) Hospita ~ ization Surgeon fees Consultations Diagnoses Drugs Nursing home Other Total direct Absenteeism Disability Mortality Total indirect Total 1977 571 55 41 60 106 11 2 846 362 363 218 - 1789 Cimetidine Effect -22% -25% -11% -9% +25% lo lo -17% -20% -24% -11% -20% -18% What hard economic data do we have? One kind is from clinical trials of cimetidine in ulcer disease, those done to prove efficacy and safety to regula- tory authorities. Economists are intrigued by such trials, because economists almost never get to do controlled experiments, particularly the randomized double-blind kind in which nobody knows until the trial is over which group got the experimental treatment and which got the placebo. We put a simple one-line item in the U.S.A. patients' case report forms: number of days of work missed last week because of ulcer disease. That is about all gastroenterologists would take time to ask. Figure 1 shows the results from a subset of work-missing patients in the clinical trial. The horizontal axis shows the pretreatment through six-week-treatment points. The vertical axis shows the average number of work days missed per , · . . am. · . - .- . . . O . patient ner week. The cimetidine and placebo groups start off about equal, missing about three and a half to four days per week for each patient. By the end of the second week, the cimetidine group was averaging about one day of missed work and the placebo group about two. The difference holds through the end of the trial. When the results were published by Drs Ricardo-Campbell and Wardell (1980), they expressed the effect of +5 1 C'met~d~ne . -N ~ 39 P'ocebo ~N5 27 _ —\\ PlocebO \ ~ N 26 _ \ \ PloceOo · N=26 C'met,c,ne ash 39 If C'met~d~ne N 38 1 1 1 Go PloceDo N 20 C,mel,d,ne oN 26 1 2 3 4 5 P'OceDo · N 8 C,met~d~ne °/V: 1 i 6 0 1 Treatment period (weeks) Figure 1. Average time lost from work per patient per week.

APPENDIX A: PROFILES 3 ~ A: - O C_ _# C a' an, ~ a) O CL ~ ~ _ C E ' ._ ._ 0 0 ~ ~ a, ~5 4F 3 - n=36, . n = 37/ / * * 1 ~ / ~ n = 26 //n =26 V , 1 0 1 2 - n=24 Cimetidine ~ _ * Placebo `. n =8 1 1 1 1 1 3 4 5 6 Treatment period ( weeks) Figure 2. The solid line connecting data points at pre-, 1 and 2 weeks indicates that data from these weeks were common to all three studies (i.e. 2-, 4- and 6-week). In contrast, data from weeks 4 and 6 were not common to all three studies. Hence a broken line connects the data points at weeks 4 and 6* (TLW = Time Lost from Work.) cimetidine in terms of improvement in worktime and inverted the data accordingly, as shown in Fig. 2. At the same time, in Sweden Drs Bodemar and Walan asked the same question of ulcer patients during a year-long double-blind trial of cimetidine maintenance therapy. Sixty-eight patients took part, 32 on cimetidine and 36 on placebo. Number missing work Work-days lost Average workdays lost per patient Cimetidine 400 mg twice daily (32 patients) 1 79 2.8 Placebo twice daily (36 patients) 23 1405 49.3 As reported in the Lancer (Bodemar and Walan, 1978), these figures tell us that one of the 32 cimetidine patients was off work for 79 days, giving a mean of 2.8 days per patient; while 23 of the 36 patients on placebo were off work for a total of 1405 days, giving a mean 49.3 workdays missed per patient during the year. This is an outstanding difference. Drs Bodemar and Walan went further and noted how many in each group went to surgery. With recurrences With two recurrences With complications Receiving surgery Cimetidine 400 mg twice daily (32 patients) 6 (Woo) 1 (3%) o 1 (3%) Placebo twice daily (36 patients) 30 (83%) 12 (demo) 4 (11%) 15 (42%) We see that recurrences were much less frequent in the cimetidine group - 19% versus 83% - leading to only one case of surgery versus 15 in the placebo group. This has obvious economic implications for the health care system. Is our cost-reduction Question answered by such findings? Unfortunately not. While randomized clinical trials have internal validity and therewith clearly isolate cause and effect, they are not necessarily valid externally in the community. At 459 least three artificialities of the controlled conditions in most randomized trials limit projection to average conditions in the 'real world'. First, although patients are assigned at random to treat- ment or placebo, those patients are not obtained initially in a random manner: they must meet certain disease characteristics, often tending toward more severe status. Second, the patients are regularly observed and examined medically and are required to take their medication according to a strict protocol. Third, placebo is not a common alternative in medical practice; most doctors will give an active drug regimen of some sort. Is it not possible, then, to do a randomized experiment in the community itself? We can with consumer products, in test marketing for example, or with technologies like insulin infusion pumps or water fluoridation; but with prescription drugs it is probably impossible. Once the drug is approved legally as safe and effective, based on the double- blind clinical trials, it is known and demanded. We cannot dictate use in a randomized design, allowing it in Liverpool and denying it in Manchester, for instance. Thus, we are hampered in the pre- approval stage by artificial conditions and in the post-approval stage by the impossibility of random- ization. It is ironic, in a way, that drugs, because look-alike placebos can be easily supplied, must be proven efficacious in controlled trials, whereas vast- ly more expensive and drastic intervention like heart-bypass surgery, where treating with a placebo is much more difficult, have no approval require- ments at all. What, then, do we turn to for hard data on the economic effect of cimetidine in the community? The answer is to epidemiology, meaning the study of disease events in a natural population. As Prof. A. J. Culyer, the eminent health economist, has said: 'The first essential for a cost-effectiveness study is good epidemiology.' Ulcer disease seems to have been declining for ten to twenty years. At least, deaths, hospitaliza- tion and surgery due to ulcer have been declining in various populations. No one knows why, although this writer's personal guess is that improved treat- ment, including tranquilizers, and exclusion of non- ulcers through more specific diagnosis have contri- buted. In any case, if cimetidine has affected any of these events, they must be found to have fallen, or fallen faster, after its introduction. Its adoption in most countries, it should be pointed out, was rapid and extensive. Typically, use occurred in over 50~o of ulcer patient visits within six to nine months after market introduction. The opportunity for an effect was indeed present. Figure 3 shows the first of several time-series suggesting that an effect has occurred. We see here the number of operations for duodenal ulcer per- formed over the last several years by a group of six hospitals in the UK. The data, from Dr Wyllie et al., appear in the Lancet (1981). Cimetidine was

460 ASSESSING MEDICAL TECHNOLOGY Cimetidine 18 000 marketed 15 000 .—~ 500 400 o q} >a ~ 300 In o - o can o 200 100 O _ Figure 3. Operations for duodenal ulcer by a group of six medical centers in the US from 1972 to 1980. introduced at the end of 1976. We see a sharp drop in operations in the following year. The trend line would have predicted a much higher number than that observed. By the ruler and eyeball method, the average difference between the expected and observed points is roughly 32% during the four- year cimetidine period. Figure 4 shows surgery data through 1979 from another area of the UK, the Northern Health Au- thority, collected by Venables (1981), a surgeon at Newcastle-on-Tyne. Though not as striking as in the previous data, the steeper drop after cimetidine is apparent. Moreover, no sign of a rebound in ulcer surgery is seen. Mr. Venables has presented data through 1978 for all of England and Wales, and these are displayed in Fig. 5. Note the drop in surgery in 1975, before cimeti- dine was introduced. Such are the anomalies to be reckoned with in time-series analysis. The explana- tion, according to Venables and others, is a labor dispute, a kind of strike, among younger physicians in 1975. We can see that general surgery for all conditions, not just ulcer, declined in that year C imetidine 200OI c '200 L \ o ._ - E o 1000 800 I I 1 1 1 1 _ Cimetidine Coo 9000 6000 3000 ) ·' ' I 1 1 1 1 1 1 i , , , , , , , , 1972 1974 1976 1978 1972 1980 1 1 1 1 1 1 1 1 +1~3 - 1~7 % - 6 1 + 1 4 +06 +06 +74 -22 ¢~_. All operations .~—Vagotomy All general surgery Figure 5. Operations for duodenal ulcer in England and Wales (HIPE) from 1971 to 1978. (-6.1%) and then rebounded in 1976, along with the ulcer surgery (Hospital In-Patient Enquiry, OPCS, UK). In many cases it can be postponed. Again, with ruler and eyeball, the drop below trend following cimetidine can be calculated at 21%, averaged during 1977 and 1978. It is time to raise the post hoc ergo propter hoc fallacy to remind us that because the sharp drop in surgery followed cimetidine it was not necessarily caused by cimetidine. No one has observed other sudden changes in therapy or the health care system that might explain the drop, but theoretically they may exist. The following data from the United States may elucidate causality. Figure 6 illustrates the number of partial gastrec- tomies and vagotomies performed in the United States over the last several years. The data were obtained from the National Center for Health Sta- tistics by Dr Fineberg of Harvard and appear (through 1979) in the Lancet (1981~. Vagotomy and partial gastrectomy are the leading operations for ulcer and a clear indication of the trend in ulcer I30 _. ,,l20~ ~. Oloot i'T1 u, 90 _ c , 80 _ O \ All operations 2 O Before cimetidine O V~O—~ ~ 70 - 0 after cimetidine O , . , . . . Vogotomy 60 I 95 % confidence interval 400 971 1972 1973 1974 1975 1976 1977 1978 1979 O I 1 1 1 1 1 1 1 1966 1968 1970 1972 1974 1976 1978 1980 Figure 4. All operations for duodenal ulcer in the Northern Health Region of the UK from 1971 to 1979 (excludes perforations). Figure 6. Partial gastrectomy and vagotomy surgery in the United States from 1966 to 1980.

APPENDIX A: PROFILES Table 4. Selected Abdominal Surgical Procedures in the United States: Rate per 10 000 Popula" tion ~40 120 100 Procedure 1970 1975 1976 1978 a, E30 All abdominal surgery 122 138 133 132 o Partial gastrectomy and vagotomy 6 5 5 3 ~ Appendicectomy 16 15 14 14 O 60 Cholecystectomy 18 21 21 20 Herniorrhaphy 25 26 24 24 Source: National Center for Health Statistics, National Hospital Discharge Survey. surgery. Had the trend continued as expected, the dashed line with its confidence bracket would repre- sent the number of operations in 1978. Cimetidine was introduced in the fall of 1977. The actual number of operations in 1978 was much lower than expected, as shown. There was a rebound in 1979 but not up to the prior trend line The 198() Joint (added after a personal communication from Dr Fineberg) is down again, strongly suggesting that the level of procedures has established itself below the prior trend line. Note that cimetidine was intro- duced a year later than in the UK but that the drop in surgery again followed. This temporal rela- tionship greatly strengthens the probability that cimetidine caused the drop. The data provided in Table 4 from Dr Fineberg's article further reinforce that probability. We see the number of appendectomies, cholecystectomies, and herniorrhaphies over the same period and find no decline in the rate per 10 000 population, and none in all abdominal surgery. Only ulcer surgery drop- ped. This appears to rule out general changes in health care procedures as the cause of the dron. Again, it should be pointed out that during 1978 in the United States cimetidine usage grew rapidly, with prescriptions occurring in over 50% of that year's office visits for ulcer. Dr Fineberg's data on vagotomy and partial gastrectomy show surgery for both duodenal and gastric ulcer. However, in the United States cimetidine had not yet been cleared by the FDA for gastric ulcer. Thus more precise data on duodenal ulcer only are desirable. They are provided by Dr Murray Wylie of the University of Michigan and appear in the Journal of Clinical Gastroenterology (Wylie, 1981). Dr Wylie's trend data include all operations for ulcer, not just vagotomy and partial gastrectomy; and only operations performed on patients hospital- ized with an ulcer diagnosis are counted. The data come from a nearly constant cohort of 790 hospitals across the United States. Figure 7 shows the trend in hospitalizations for duodenal and for gastric ulcer. We see that for duodenal ulcer the trend has again been downward and that in 1978, the year after the introduction of cimetidine, it did not drop faster than before. Gastric ulcer hospitalizations appear essentially level. 461 Duodeno' ulcer ~ \Gastric ulcer 40 _ 30 , 1, ', ~ . ~ 1972 1974 1976 1978 Year of discharge Figure 7. Time trends in the United States in hospital discharge rates for duodenal and gastric ulcer per 100 000 population, by diagnosis and year, short- term hospitals, from 1971 to 1978. (Source: National Center for Health Statistics, Hospital Discharge Survey.) As shown in Table 5, Dr Wylie finds, starting in 1977, a growth in the share of admissions with complications, meaning bleeding or a perforation of the intestinal wall. He then notes (Fig. 8) the percentage of ulcer admissions receiving gastroin- testinal surgery. Again a sharp drop in the rate of surgery following cimetidine's introduction is seen, revers- ing a slightly rising trend in the rate. As Dr Wylie points out, the greater share of complicated cases would normally be expected to produce more surgery, not the lesser amount observed. The drop did not occur in gastric ulcer, neither complicated nor uncomplicated, for which cimetidine was not approved. However, in duodenal ulcer the drop occurred in both the complicated and uncompli- cated kinds. Also, the drop started quite promptly after the introduction of cimetidine. Dr Wylie also noted the case fatality rate among hospital admissions (Fig. 9). He observes that at a time when the mix of cases changed to increase the risk of dying-that is, from the greater share of hemorrhages and perforations - the death rate clearly dropped, particularly so in 1978 for duoden- al ulcer. The decline in ulcer surgery is suggested as the cause~of this drop. Dr Wylie also finds that the Table 5. Percentage of patients with complications of Duodenal and Gas- tric Ulcer Admissions to 790 PAS Participating Hospitals in the United States Year of admission Duodenal ulcer 1 974 1975 1 976 1 977 1978 1 979 . . . 33.0 32.9 33.1 35.4 37.7 39.6 Gastric ulcer 32.5 32.8 32.6 34.5 37.1 37.4

462 o 45 To 35 30 25 20 o 0, ~ 5 _ c a' 10 _ Cimetid i ne ~ ~~ 2 ^~ _~\ , 3 4 · 1 1 1 1 1 i 1 1 1 1974 1975 1976 1977 1978 1979 Figure 8. Percentage operated upon duodenal and gastric ulcer admissions to 790 PAS participating hospitals in the United States by year and quarter of admission, 19701979. (1) Gastric ulcer with com- plications; (2) uncomplicated gastric ulcer; (3) duodenal ulcer with complications; (4) uncompli- cated duodenal ulcer. average length of hospital stay fell more rapidly after 1977. In all, Dr Wylie concludes, 'the use of cimetidine, plus the high expectations before its impending release, probably caused the change in trends documented in this study'. Finally, Fig. 10 provides one other time series in the United States, useful because it shows the frequency of ulcer surgery as a rate per population. The small state of Rhode Island collects such data and thus controls for demographic shifts which theoretically may confound results. The data are from a study by Rhode Island Health Services Research (Norton et al.., 1980) and have been submitted for publication. We see the same drop after cimetidine's introduction. The number of vagotomies and partial gastrectomies for duodenal ulcer per 100000 population was projected along the trend line but actually fell well below it, saving about 10 operations per 100000 residents of the ,,, 60 .° 50 v, E c' o o - C1 c - c, 40 30 20 10 Cimetid ine ~ 1 ~ _ ~ n _ _ I 1 _ ~ 5 o 1974 .1975 1976 1977 1978 1979 Year of odm ission l Figure 9. Deaths per thousand admissions in the United States of duodenal and gastric ulcer by presence or absence of complications, by year of admission, 19701979. (1) Complicated gastric ulcers; (2) complicated duodenal ulcer; (3) uncompli- cated duodenal ulcer; (4) uncomplicated gastric ulcer. ASSESSING MEDICAL TECHNOLOGY sot 40 30 20: I0 _ A l :__ I · Ulcer surgery ~ t~ Linear ~ I regression · Lineor regression line c ~ ·ge. · Neoplasm pa I \. E I ~.--.-T-. . . u 1972 1973 1974 1975 1976 1977 1978 1979 1980 Figure 10. Rates per 100 000 persons of partial gastrectomy and/or vagotomy for Rhode Island residents for the twelve months ending 31 August 1973 through 1980. state in 1978 and 1979, and somewhat more in 1980. No sign of a rebound is seen. Since partial gastrectomies are sometimes done for cancer, all cancer cases have been separated and appear along the bottom of the graph. This serves as a kind of control in the data, and we see no drop after . . . c~met~d~ne. So much for the epidemiologic data in the United States. In this writer's view, simply by reproducing the UK data one year later-given that cimetidine was introduced in the United States one year later than in the UK- evidence clearly is established for cimetidine as the cause of the sudden drop observed. The same decline can be found in the two other countries where time-series data have been col- lected so far. First, in France data were collected by Lambert-Yves Conseil (1980), research consul- tants, in a special survey of 25 university and regional hospital centers (CHU and CHR). The results have not yet appeared in the medical literature: 1976 1977 1978 1979 Number of ulcer operations 1456 1376 988 1026 1976 base = 100 100 95 68 70 Although the series is shorter than in the United States, the number of operations for peptic ulcer dropped sharply after the introduction of cimetidine in the fall of 1977. There were two other samples of hospitals supplying such data. Table 6 shows the findings for each. The drop also occurred in medium-size hospitals and in private clinics; although the decline in 1977 in the former is difficult to explain and may be spurious. Appendec- tomies and cholecystectomies were recorded as a control and Rational projections made (Table 7). As in the United States' data earlier, we see no fall

APPENDIX A: PROFILES Table 6. Number of Operations for Duodenal and Gastric Ulcers in France 3500 3000 Eight medium-size public hospitals 2500 1976 1977 1978 1979 2000 Number of operations 202 152 142 124 ~ 500 1976 base = 100 100 75 70 61 loo Twelve centers~for private care 1976 1977 1978 1979 500 Number of operations 353 1976 base= 100 100 335 95 229 254 65 72 in these other gastrointestinal interventions, only in surgery for ulcer, down 30%. Next, and last, the Netherlands has excellent data at the national level on most aspects of medical care. The data on ulcer surgery have been collected by the Netherlands Economic Institute and are presented very briefly in Econom~sch Statist~sche Berichten (Bulthuis, 1981). A full article will be published based on a presentation by Bulthuis (1981). Hospitalization for ulcer, in terms of both admissions and length of stay, has been declining in the Netherlands, as have total operations for ulcer. Figure 11 details the operations performed for Table 7. National Projection of Appendectomies and Cholecystectomies in France ~ 979 340 000 85 000 10 700( - 30%) Appendectomies Cholecystectomies Ulcers Operated 1972 1976 333 000 340 000 69 000 85 000 15 600 15 600 duodenal ulcer patients since 1972, with the total through 1980. Both gastrectomies and vagotomies dropped sharply after cimetidine was introduced in the fall of 1977. The latter operation was becoming more popular but reversed its uptrend. Figure 12 shows operations for gastric ulcer, for which cimetidine was approved. Again, the same drop is seen, with no sign of a rebound in 1980 (updated NEI report in press). Because the Nether- lands have impressively complete data, Dr Bulthuis was able to do a multiple regression analysis of a number of variables possibly causing the drop in 463 Total number \<perations _ , - ' Cimetidine introduced _ _ _ Partial ~ gastrectomy _--~ ~ :~ | Vagotomy Caner —_ operations ~ | ~ I 1972 1973 1974 1975 1976 1977 1978 1979 1980 Figure 11. Trend in the number of operated hospital- izations for duodenal ulcer in the Netherlands, by type of operation. surgery. Those variables include fiber-optic endos- copies ( a popular new procedure for looking into the gastrointestinal tract with a tube), drug usage, physician visits and even a change in 1975 in government policies toward hospital reimburse- ment. While no absolute proof of cause and effect, multiple regression analysis allows the contribution of the different variables to the change in trend to be calculated and tested for statistical significance. Table 8 shows the findings of Dr Bulthuis. The table shows the only two things accounting for the decline in ulcer operations between 1972 and 1979, the general trend and cimetidine. In admissions for gastric ulcer without surgery, the trend explains all of the reduction, some 300 operations. With surgery, cimetidine and the trend each contributes equally to the reduction. In 2300 2100 ~900 i 700 ~ 500 1300 100 900 400 200 Cimetidine ~ A| Toto! number Woof operotions _- —_ _ ~~~~ ;:,~~ gostrectomy N _ , Other operations O —-—t—— I I I I I ~ 1972 1973 1974 1975 1976 1977 1978 1979 1980 Figure 12. Trend in the number of operated hospital- izations for gastric ulcer in the Netherlands, by type of operation. Table 8. The Reduction in the Number of Hospital Admissions in the Netherlands for Peptic Ulcer Disease Attributable to the Established Trend and to Cimetidine, 197~1979 Hospital admissions without surgery Hospital admissions with partial gastrectomy or vagotomy Hospital admissions with other operations Total Gastric ulcer Duodenal ulcer Peptic ulcer {total) Cimetidine Trend Cimetidine Trend Cimetidine Trend n.a. 300 n.a. 1700 n.a. 2000 400 400 1000 n.a. 1400 400 n.a. n.a. n.a. 500 n.a. 500 400 700 1000 2200 1400 2900

464 ASSESSING MEDICAL TECHNOLOGY duodenal ulcer without surgery, the trend accounts for the entire reduction; whereas with surgery, cimetidine accounts for all the 1000 operations avoided. To summarize the international data so far. (1) Hospitalization and surgery are major components of the direct cost of ulcer disease. (2) Randomized double-blind clinical trials have proven that cimeti- dine not only heals ulcers and prevents their recurrence but also can keep ulcer patients working and away from surgery. (3) Cimetidine was rapidly and widely adopted in the treatment of ulcer disease. (4) The reduction in surgery suggested by Bodemar and Walan's clinical trial of cimetidine has now been clearly observed in a number of different data series covering four countries and two different years of introduction. (5) Factors such as abdominal surgery generally and other specific variables examined do not explain the sudden reduction seen. Surely, until some other explana- tion is provided, we should accept cimetidine as the cause of the recent sharp drop in ulcer surgery. CIMETIDINE AND TREATMENT COST REDUCTION Now, what about costs? As mentioned above, a conservative approach is forced on us. Psychosocial benefit to patients from changes in treatment methods, the gain in wellbeing, is too intangible to measure in money terms. We could quantify the gain in terms of total years of wellness, or as Dr Weinstein puts it, 'quality-adjusted life years' or more simply in terms of operations and absenteeism avoided. If a dollar spent on a new technology produces more of these indications of health than a dollar spent on another technology, then the newer one is more cost-effective. Thus, one technology may increase costs but nevertheless be more cost-effective than another. It may offer more health for the money. While that sounds reason- able, budget administrators today simply have less money to spend and want technologies to help them to cut expenses. So, we come back to the cost-reduction criterion, which perhaps only the luckiest of cost-benefit analysts should grapple with. Does cimetidine reduce the treatment costs of ulcer disease? Most epidemiological studies do not go into costs, but three of the above do: the French, the Rhode Island and the Dutch. The French study (Lambert-Yves Conseil, 1980) relates its trend data in the sample of hospitals to national counts of ulcer surgery to project a national figure in 1979 of 4900 ulcer operations avoided. Using national cost schedules for operations and for a hospital day as well as the average length of stay of ulcer surgery patients, the study calculates a national saving in hospital costs in 1978 of about 43 million francs. Table 9. Charges for Hospitalization of Blue Cross and Blue Shield Patients in Rhode Island, January-June 1976 (in dollars) Blue Cross Routine Ancillary charges charges Partial gastrectomy 1775 1519 Vagotomy 1824 1210 Ulcer and ulcer-related without ulcer surgery 1189 465 1654 Source: Blue Cross and Blue Shield of Rhode Island and CPHA Abstracts. Blue Shield Surgery physicians' fees Total 700 3994 535 3569 The above is based on the straightforward assumption that none of the patients avoiding surgery go into the hospital at all. The data on trends in total admissions for ulcer, surgical or not, do not as yet show statistically significant sharper drops after the introduction of cimetidine; however, the relatively few ulcer surgery candidates - perhaps 15% or 20~o of ulcer admissions in the United States-could indeed all stay out of the hospital without affecting total admissions to a statistically significant degree, given the natural yearly variabil- ity of the trend line. Of course, it is also possible that most of the patients saved from surgery nevertheless enter and stay for some time in the hospital for diagnosis, bed rest, other treatment or observation. With that in mind, we return to the Rhode Island study (Norton et al., 1980). Table 9 shows the cost of surgical and non-surgical stays in Rhode Island in 1976. These costs are averaged from the records of reimbursement payments to hospitals and surgeons and anesthetists in Rhode Island for individuals hospitalized under Blue Cross and Blue Shield, the dominant private health insurance programs in the United States. A surgical stay, which is longer, of course, generates over twice the reimbursement costs of a non-surgical stay for ulcer. A weighted average of the vagotomy and partial gastrectomy costs and the non-surgical costs were adjusted upward for inflation through 1978, giving the figures of Table 10. This shows that if the surgical candidate does not enter the hospital at all, $4874 is saved. If he enters but avoids surgery, $2799 is saved. Recall from Table 9 that in Rhode Island about ten operations per 100000 population were avoided in 1978 after the introduction of cimetidine. If this rate is directly applied to the United States population of about 215 million people the figures in Table 11 emerge. We calculate a saving of about $104 million if hospitalization for surgery candidates is avoided altogether and about $60 million if they are hospitalized with only medical treatment. The Rhode Island research group was able to make some refinements in the projection by adjusting for Rhode Island's higher per capita share of health expenditures versus the United States average. The more accurate national projections of cost savings

APPENDIX a PROFILES Table 10. Charges per Hospital Stay in Rhode Island (in dollars) With partial gastrectomy or vagotomy {weighted average) Ulcer and ulcer-related without ulcer surgery Savings of . . . aamlsslon avoiding ulcer surgery 1978 2006 793 2799 a Inflation from 1976 to 1978: routine plus ancillary charges=+25.5% (R.l. Blue Cross average daily hos- pitalization costs); surgery physician's fee=+17.7% (physician services, consumer price index) Routine plus Surgery ancillary physicians' charges fees Total 1 976 3252 1 978a 4081 1976 1654 1 978a 2075 674 3926 793 4874 1 654 — 2075 are shown as about $97 million and $59 million. The lower figure might be termed a worst case for 1978. For 1980, the range is $82 million to $135 million. Finally, we turn again to data from the Nether- lands. Table 12 shows the reductions in days and guilders resulting from the reduced operations in that country. The reductions are separated into those explained by trend and by cimetidine. Using cost and fee schedules in the Netherlands, Dr Bulthuis has translated the days into the costs shown (Bulthius, 1981). We see that the cost reduction contributed by cimetidine comes to 10 million Builders in 1978 and 1979 together. Drug costs for treating ulcer were increased by 5.5 million, leaving a net reduction in ulcer treatment costs contributed by cimetidine of 4.5 million Builders. Dr Bulthuis' conclusion is that new technologies in health do not necessarily increase treatment costs. More importantly, perhaps, his analysis shows what can be learned from multiple regression analysis when sufficient data are avail- able. In a sense, he shows what must be learned if we are to put the obvious purchase or reimburse- ment costs of a technological innovation into the Table 11. Projection of Rhode Island Savings to National United States Popula- tion US population 1 00 000 x ten operations avoided per 100 000 x $4874 saved if no admission or x $2799 saved if admission but no surgery = 215 000 000 = 2150 = 21500 = $104791 000 = $60 178 500 Adjusted for Rhode Island versus US per capita ex- penditures on hospital and physician services: $104 791 000 ~ $97 175 500 $60 178 500 ~ $59 162 500 465 Table 12. Contribution of Factors in the Nether- lands Responsible for the Decreasing Importance of Hospitalization Costs among the Total Costs of Peptic Ulcer (million Builders) (1) Decrease in number of hospitalizations since 1972: (a) Due to trend, non-operated: 85 500 days = 22.0 (b) Due to trend, Operated: 37 500 days = 10.8 Due to cimetidine, Operated: 30 000 days = 8.7 Total operated 1 9.5 Subtotal 41.5 (2) Decrease of operation costs (not included under (a) and (b) above) Due to trend Due to cimetidine 0.8 1.2 Overall due to trend Due to cimetidine Drug costs 33.5 10.0 -5.5 4.5 million guilders 2.0 Total 43.5 perspective of the much less obvious cost reductions it may cause. The final data presented are unique. They come from the computerized reimbursement records of Michigan Medicaid, the state's health care program for the poor and disabled, and were analysed by the eminent American health economist, Dr Burton Weisbrod of the University of Wisconsin, along with his colleague, Dr John Geweke. They have been submitted for publication (Geweke and Weis- brod, 1981). The Medicaid records are invaluable, sinceithey show all treatment events and costs as they occur for each patient in the program. Drs Weisbrod and Geweke constructed an experiment retrospectively after the marketing of cimetidine. They compared all ulcer-related costs of cimetidine- treated patients with those of ulcer patients not treated with cimetidine, that is, treated tradi- tionally. The costs were counted starting with a duodenal ulcer episode and continuing for the remaining months of the patient year. Now, comparing two such groups after they have manifested themselves naturally in the community can be faulty and very misleading, because the cimetidine and the tradi- tional treatment were obviously not assigned at random. Unlike the case of most clinical trials, selectivity bias will almost certainly arise. In fact, the researchers found that cimetidine was given to the more severe patients, that is, those who had histories of much higher reimbursement costs prior to the initiation of cimetidine. Obviously, a meaningful comparison must be based on equally severe or costly cases in each treatment group. Therefore, Weisbrod and Geweke controlled for severity by regression analysis, meaning in this instance adjusting treatment cost averages for the two groups to start out equal. Their findings may be displayed as in Fig. 13. The horizontal axis shows

466 $1000 $ 750 0 ~ c ._ a) ~ ° ~ $ 500 ~ x ._ _ 0 0 — , ~ ~ S 250 I Control grou P 1 ll J I · · group 1 6 Months from initial intervention 12 Figure 13. Average annual Michigan Medicaid ex- penditures per patient with duodenal ulcer, by month of expenditure. the twelve months following onset of the duodenal ulcer episode, and the vertical axis shows cumula- tive treatment costs for the average patient over the twelve months. The broken line shows the tradi- tionally treated patients, the solid line the cimeti- dine patients. The difference at the end of the year is $500. This is due mainly to reduced hospitaliza- tion costs among the cimetidine patients, as Fig. 14 illustrates. As all the data seen so far would have predicted, hospital charges are much lower among the cimeti- dine patients. The researchers have not yet focused on reduced admissions, surgery and lengths of stay so as to present just where the hospital savings are generated; but fewer hospital days per average patient were observed for the cimetidine croup. Also, the first month of the patient's episode is critical, since it is then that many cimetidine-treated patients avoided hospitalization altogether. Note also that physician costs are lower for the average cimetidine patient, and that drug costs are Total- $721 Physician $109 Hospital $602 Drugs S 10 Total = $221 Physician SS7 l Hospital S97 l Drugs 366b | Control Cimetidine group group Figure 14. Average annual Michigan Medicaid ex- penditures per patient with duodenal ulcer. aDoes not include antacids which are excluded from Michigan Medicaid; b includes cost of cimetidine therapy. ASSESSING MEDICAL TECHNOLOGY Table 13 Estimated reductions in rate of surgical/ physician intervention (%) Pessimistic (19.5) Best guess (39.0) Optimistic (69.5) Savings per capita (cimetidine and non- cimetidine) (patients) in duodenal ulcer related care s % 68 9.4 187 26.0 375 51.9 . ... . higher. One caveat, however, is that Michigan Medicaid does not reimburse antacids, the only widely used alternative to cimetidine in the United States. If antacids were included at recommended doses, the $10 drug costs for the non-cimetidine patient would be at least $50 higher, and somewhat higher for the cimetidine patient, who may well take some antacids in the early days of the episode. Finally, in a sensitivity analysis (Table 13), the researchers calculate what the total net savings per duodenal ulcer patient would be if various reduc- tions in the frequency of surgical and physician intervention were achieved. We see that in the pessimistic case $68 in treatment costs are saved for every duodenal ulcer patient in the Medicaid program. This is net, with the cimetidine costs included. Actually, a reduction in frequency of surgical intervention among the cimetidine-treated patients would seem to fall between 39% and 69.5%. This is because we have observed in the trend-analysis data shown earlier an overall average reduction in ulcer surgery of about 25% below the expected trend line. This, of course, represents entire populations, including both cimet- idine and non-cimetidine patients. If a 25% reduc- tion is seen for both groups together, then the reduction for the cimetidine group alone must be higher than 25%. If cimetidine over the trend periods studied was used in half the duodenal ulcer patients, then a 50% reduction in surgery among the cimetidine patients would produce the 25% reduction below trend that we have seen in the time-series data. Therefore, perhaps a $250 savings per patient has been realized in the entire duodenal ulcer population-representing the present writer's extrapolation from the Weisbrod-Geweke findings. In any case, let us conclude with a quote from the researchers: v , ~ The empirical results show that treatment with cimetidine is an expenditure reducing alternative compared to previously existing therapeutic in- tervention... The approach used... shows the new technology to reduce expenditures by some 70 percent... even our more conservative ap- proach predicts expenditure savings attributable to cimetidine.

APPENDIX A: PROFILES CONCLUSION To summarize, the reduction in surgery-related hospitalization costs due to cimetidine use in ulcer disease has ranged from about 10 million guilders over two years to 43 million francs in one year to $135 million per year. From these some increase in drug costs needs to be subtracted; however, from the Dutch and the Weisbrod-Geweke data, the final result shows a net reduction, or savings, in total treatment costs. Though a businessman and market researcher, not an academic economist, the writer cannot resist speculating on some implications for society of the data we have seen. First, it is not only sick people and their families who have benefited from the innovation under analysis. Everyone else, insofar as they pay taxes or medical insurance premiums, ultimately benefits through lowered, or less in- creased, total treatment costs. Second, net benefits from a new drug are not unprecedented. To quote von Grebmer (1981) citing Stahl: 'Within the available factors of production for health (e.g., hospital care, physicians' services, medical therapy) the highest productivity increases have originated and will originate from technological advances in drug therapy.' Third, how will this continue so that society obtains for itself the benefits in such areas as cardiovascular disease, cancer and arthritis that cimetidine provided in ulcer disease? The author believes that the most efficient way is through continued investment by industry in the research and development of new chemical entities against disease. We have seen how that worked with cimetidine. Fourth most Western economists would probably find it elementary that the induce- ment to intensive drug R & D is the expectation of profit. What is not widely understood is that the profit on some individual products must be high to offset those new chemical entities which after marketing never repay their R & D investment. Recent data (Joglekar et al., to be published) show that of the new chemical entities introduced in the United States since 1963, two out of three have not sold enough worldwide to repay capitalized R & D costs of the average marketable new entity-some $54 million dollars as of 1978 (Hansen, 1979). Thus the only thing that makes new drug R & D an acceptable ramble-for a large firm able to afford it - is the chance of a 'big winner'. Fifth, and last (and on admittedly treacherous ground), what might the savings in total treatment cost, such as those from cimetidine use in ulcer disease, mean for the price of the drug producing those savings? Just posing the question raises the possibility, at least, that if we seek efficiency in producing health for a population over a long run, we should~accept the notion that some of the savings produced by the drug should be channeled back to the innovator. The probability of that happening, ire the case of an innovative firm hovering on the brink of more or less drug R & D, could induce a $54 million investment that other- wise would not occur. Let us reverse things. At one early point the H2 research program which pro- duced cimetidine was almost shut down; there were limits on research expenditure. The large market for the specific product, cimetidine, was not obvious at that stage. Would the research expendi- ture have continued if the innovating firm had believed that the price of cimetidine would be held down to that of pre-existing products, many of them generic? Apparently, there is no straightforward economic law telling how much, if any, of the savings realized should go to the innovator-so as to incite the maximum amount of future benefit for society at the lowest possible cost- but the expense and risk of drug R & D and the need for 'big winners' to finance it make it reasonable for economic and political leaders to recognize the possibility of the future innovator sharing equitably . . In any savings he may generate. REFERENCES G. Bodemar and A. Walan (1978). Maintenance treatment of recurrent peptic ulcer by cimetidine. Lancet (25 February). R. Bulthuis, et al. (1977). Present Cost of Peptic Ulceration to the Dutch Economy and Possible Impact of Cimetidine on this Cost. Netherlands Economic Institute, Rot- terdam. R. Bulthuis (1981). Medicines for health care? Economisch Statistische Berichten 66e Jargang, No. 3298 (25 March), Rotterdam. R. Bulthuis (1981). Surgery trends and costs of peptic ulcer disease in the Netherlands before and after the intro- duction of cimetidine. Proceedings of NEI-SKF Sympo- sium, Amsterdam, March. V. Chandler and G. van Haunalter (1977). The Cost of Ulcer Disease in the United States. Stanford Research Insti- tute, Menio Park, Cal. H. Fineberg and L. A. Pearlman (1981). Surgical treatment of peptic ulcer in the United States. Lancer (13 June). R. W. Hansen (1979). The pharmaceutical development 467 process: estimate of current development costs and times and the effects of regulatory changes, in Issues in Pharmaceutical Economics, ed. by R. I. Chien, Lexington Books. P. Joglekar, et al. Investment in the research and develop- ment of new chemical entities: the risks and returns. Manuscript in preparation. J. Norton, et al. (1980). The Effect of Cimetidine on Peptic Ulcer Disease in Rhode Island. Rhode Island Health Services Research, Inc., Providence, R. I. The 1980 data are from an update report of 26 May 1982. M. Olitsky, et al. (1978). The Impact of Cimetidine on the National Cost of Duodenal Ulcers. Robinson Associates, Inc., Bryn Mawr, Pa. R. Ricardo-Campbell and W. Warden, et a/. (1980). Prelimin- ary methodology for controlled cost-benefit study of drug impact: the effect of cimetidine on days of work lost in a short-term trial in duodenal ulcer. J. Clin. Gastroenterol. 2, 3701. C. W. Venables (1981). Surgery and hospitalization trends in

468 ASSESSING MEDICAL TECHNOLOGY the United Kingdom before and after cimetidine. Pro- ceedings of NEI-SKF Symposium, Amsterdam, March. K. van Grebmer (1981). Competition in a structurally changing pharmaceutical market: some health econo- mic considerations. Soc. Sci. Med. 15C, 77-86. B. Weisbrod and J. Geweke (1981). Assessing technological change: the case of a new drug. To be published. Used with permission of the authors. M. Wylie (1981). The complex wane of peptic ulcer. I. Recent national trends in deaths and hospital care in the United States. II. Trends in duodenal and gastric ulcer admis- sions to 790 hospitals, 1974 1979. J. Clin. Gastroenterol. 3, 327-39. J. Wyllie, et a/. (1981). Effect of cimetidine on surgery for duodenal ulcer. Lancet (13 June). Y. Lambert (1980). Trend in Ulcer Surgery, Gastrointestinal Hemorrhages, Appendectomies and Cholecystectomies 197~1979. Lambert-Yves Conseil, LaGarenne, France.

Institute for Health Policy Studies University of California, Sari Francisco 1326 Thirc! Avenue San Francisco, CA 94143 (415) 666 4921 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X X X X X X X X Ethical/Legal/ Social Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems Organizational/Administrative X X X X X Stage of Technologies Assessed X Emerging/new X Accepted use Possibly obsolete, outmoded A p plication of Technologies X Prevention X DiagnosiS/screening X Treatment Rehabilitation Assessment Methods Laboratory testing Clinical trials X Epidemiological and other observational methods X Cost analyses X Simulation/modeling Group judgment X Expert opinion X Literature syntheses Approximate 1985 budget for technology assessment: $700,000* * The total Institute budget for the period is approximately $2.5 million. Of this, about 40 percent is devoted to training fellowships. Approximately $700,000 is devoted to assessment of medical technologies, and the remainder is devoted to other health-related studies. INSTITUTE FOR HEALTH POLICY STUDIES UNIVERSITY OF CALIFORNIA, SAN FRANCISCO Introduction The Institute for Health Policy Studies (IMPS) is an academic and research unit of the University of California, San Francisco (UCSF). IHPS was formerly known as the Health Policy Program. IHPS was established in 1972 within the 469 UCSF School of Medicine. The Institute con- sists of an interdisciplinary group of faculty members representing medicine, govern- ment, education, law, sociology, pharmacol- ogy, journalism, and philosophy and ethics. When established, IHPS was the only organ- ized health policy group in the nation based within a university health sciences campus, according to UCSF-IHPS. From 1972 through 1977, IHPS developed its capacity to conduct independent policy analysis and policy research and to provide

470 technical assistance, primarily to federal and state policymakers, with a major emphasis on health manpower policies; prescription drug policies; ethical issues in health care; long- term care issues; and planning, regulation, and financing issues. IHPS also began to en- gage in health services research, focusing on the cost of illness and health care, the use and cost of medical technologies, and group prac- tice and prepaid health care settings. A pro- gram of education and training for faculty and students in the health professions, law, ethics, economics, planning, public policy, and other disciplines also was developed dur- ing this period. The major initial sources of support were UCSF and the Robert Wood Johnson Foundation. Additional support was provided by federal contracts and grants from the Veteran's Administration, the Na- tional Center for Health Services Research, the Bureau of Health Planning and Resources Development, and the Health Resources Ad- ministration, as well as grants from a number of private foundations. In 1977, IHPS was awarded a 5-year grant (through April 1983) from the National Cen- ter for Health Services Research as the first national Health Services Policy Analysis Cen- ter. This grant supported the creation of a strong multidisciplinary group of faculty whose focus was on health policy issues. The Institute was formally designated as an Orga- nizational Research Unit within the School of Medicine, UCSF, in 1982, and officially changed its name from the Health Policy Pro- gram to IMPS. IHPS has formal linkages with schools and departments on the UCSF cam- pus, the UCSF hospitals and clinics, the Uni- versity of California, Berkeley, and the Uni- versity of California, San Diego. Purpose ASSESSING MEDICAL TECHNOLOGY for policymakers, program managers, and others in the field of health. To accomplish this purpose, IHPS develops formal courses for students in the UCSF schools of medicine, nursing, pharmacy, and dentistry; offers training opportunities through fellowships and internships; forms collaborative educa- tion and training programs with other insti- tutions; and develops seminars and other ed- ucational experiences for individuals and special groups in the health field. Second, health services research and policy analysis projects are undertaken by Institute faculty in a variety of areas, including the costs of health care, long-term care and chronic illness, health policies and the aged, technology assessment, and reproductive health. Third, IHPS provides informed advice to federal and state governments and other poli- cymaking bodies on ways of improving the effectiveness and efficiency of health care de- livery systems. This profile primarily ad- dresses this aspect of IMPS. Subjects of Assessment IHPS is primarily interested in topics of health services research. In recent years, IMPS's priority areas in research and policy analysis have been health maintenance orga- nizations (HMOs) and other organized health care delivery systems, cost containment, im- pact of medical technology on health care, ethical issues in health care, reproductive health policy, health policies and the aged, child health policies, prescription drug poli- cies, health manpower policies, health plan- ning, health promotion, and disease preven- tion, and health care for disadvantaged per- sons. Table A-15 lists the more than 60 research and analysis projects, including ma- jor research programs, initiated during the period 1977-1983. The IHPS has a threefold purpose. First, IHPS provides opportunities in education and training for students and practitioners in the health professions; for students and fac- IHPS addresses new, emerging, and ulty in other disciplines (e. g., law, eco- ' ' - ' ~ ~ ~ nomics, sociology, bioethics, planning); and Stage of Diffusion widely accepted technologies and modalities of health services delivery.

APPENDIX A: PROFILES 471 TABLE A-15 University of California, San Francisco, Institute for Health Policy Studies Project Listing, 1977-1983 Analysis of the Trends in the Number and Distribu- tion of Pediatricians and Family and General Prac- titioners in the United States between 1976 and 1979 Assessment of Long-Term Social Outcomes of Total Hip Replacement Changes in Medical Technology Use Over Time Child Health Policy Childhood Chronic Illness: Trends and Determinants Chronic Disease Care Among Different Specialties Commonweal-Institute Joint Research Project Competition and Complementarity in Hospital Services Competitive and Selection Effects of HMOs Competitive Impact of Prepaid Medical Plans in California Correlates of Long-Term Care Expenditure and Service Utilization Cost and Epidemiology of Catastrophic Illness Costs and Effectiveness of Neonatal Intensive Care Costs and Effectiveness of Nurse Practitioners Costs and Effectiveness of Upper Gastrointestinal Endoscopy Cost-Effectiveness of Perinatal Access and Obstetrical Access Programs Determinants of Health A Diagnosis Study of Utilization Patterns Drugs and the Elderly East Bay Hospital Perinatal Study The Effects of Selective Regulation on Competition in the Long-Term Care Industry Evaluation of New California Health Insurance Laws Exercise and the Elderly The Growth and Utilization of Intensive Care Units Health Factors Affecting Long-Term Care Policy Health Maintenance Organizations: Dimensions of Performance Health Policy and the Aged, Including Long-Term Care Health Promotion/Disease Prevention HMOs: The California Experience Hospital Cost Containment Hospital Reimbursement: Diagnostic-Related Groups Incidence of Upper Gastrointestinal Endoscopy Income and Health An Inpatient Hospice at Moffitt Hospital: A Feasi bility Study Laguna Honda Project Long-Term Care: Impact of State Discretionary Policies Long-Term Care: Implications for California's State Discretionary Policies Low Income and Health Medical Care Expenditures in the Last 12 Months of Life Medical Care Use Under Two Prepaid Plans Medical Cost Changes of Selected Illnesses, 1971- 1981 Multiple Risk Factor Intervention Trial National Service Health Care Study Nutrition and the Elderly Planning and Regulation Research Poverty and Health Prescription Drug Policy: Drug Coverage Under National Health Insurance Prescription Drugs in the Third World Prescription Drugs: Regulation, Pricing, Cost Con- tainment, Promotion, Irrational Prescribing Program for the Humane Care of the Dying Patient Program in Reproductive Health Policy Refugee Health Services/Refugee Health Manpower Relationship Between Surgical Volumes and Mor- tality Research and Analysis of Health- Manpower Issues Retailing of Health Care Services Role of Out-of-Pocket Costs in Selection of Health Insurance by University of California Employees Role of Pharmacy in Health Care in Jamaica Selection and Competitive Effects of Health Mainte- nance Organizations Social Isolation as a Predictor of Hip Fractures State and Local Long-Term Care Policy Project A Study of Differences in the Care of Arthritis in HMOs and Fee-for-Service A Study of the Interactions Between Health Planning Agencies and Area Agencies on Aging in Meeting the Health Needs of the Elderly Synthesis of Research Findings on the Operations and Performance of Health Maintenance Organizations Systolic Hypertension in the Elderly Project Third-Party Methods of Paying Physicians Why Do the Chronically Ill Stop Working?

472 Concerns Most of the Institute's technology-related projects are concerned with effectiveness; cost-effectiveness and other cost-related is- sues; and certain social, ethical, and legal im- plications of technologies. Requests From 1977 through 1983, IHPS faculty and research staff responded to approxi- mately 800 documented requests for techni- cal assistance. Nearly half of the requests were from federal policymakers or their staffs. IHPS receives requests for information and assistance from foundations, professional organizations and societies, health provider groups and associations, hospitals, employ- . . . . . ers, unions, insurance companies, unlversl- ties, health service research centers, con- sumer groups, advocacy organizations, voluntary associations, and the media. Poli- cymakers from countries outside the United States also seek information and technical as- sistance. Federal government recipients of technical assistance have included Congress, Executive Office of the President, Department of Health and Human Services, and the Federal Trade Commission. California governmental recipients of technical assistance have in- cluded the state legislature, Office of the Governor, and Health and Welfare Agency. Other technical assistance recipients have in- cluded California county and municipal gov- ernments, other states, and policymakers in countries outside the United States. Selection Selection of projects is generally made by individual faculty and staff members. Proj- ects undertaken must be within a faculty/ staff members' area of interest, consistent with the purposes of the IMPS, and subject to university policies regarding grants, con- tracts, and other arrangements with outside parties. ASSESSING MEDICAL TECHNOLOGY Process The wide variety of studies conducted by IHPS include literature syntheses, cost-effec- tiveness and cost-benefit analyses, and epide- miological studies. Through its formal rela- tionships with other university institutions, IHPS has access to clinical data for study. For instance, in a study of changes from 1972 to 1977 in the use of medical technologies for 10 inpatient diagnoses, IHPS used automated billing data from the UCSF hospital, a 560- bed teaching facility (Showstack et al., 1982~. Assessors IHPS has approximately 30 faculty mem- bers and 28 affiliated faculty, over 20 full- time research staff, approximately 40 predoc- toral and postdoctoral fellows and visiting scholars, and approximately 20 full-time sup- port staff. This multidisciplinary staff repre- sents the fields of law, pharmacology, philos- ophy and ethics, medicine, economics, public policy and administration, planning, statistics, sociology, epidemiology, political science, medical anthropology, and medical information sciences. Many IHPS faculty members have educational responsibilities in addition to their research and analysis activi- ties. As an Organizational Research Unit, IHPS offers joint academic appointments, with the primary appointment in an aca- demic department, such as the Department of Medicine. Turnaround The turnaround time varies according to the type of study conducted or other assis- tance provided. For instance, the case studies on various technologies conducted for the Congressional Office of Technology Assess- ment took approximately 6 months to com- plete. Responses to requests for technical as- sistance may take from 1 day to several weeks, and formal health services research projects are often 2 to 3 years long.

APPENDIX A: PROFILES Reporting Reporting of IHPS findings and related health policy issues is directed to three major audiences: federal and state policymakers, the health services research and health policy research communities, and the general pub- lic. From 1977 to 1983, UCSF~-IHPS faculty and research staff published 14 books, 15 monographs, 61 book chapters, and 129 jour- nal articles. The journals in which reports of IHPS studies have appeared include the American journal of Public Health, Annals of Internal Medicine, Health Care Financing Review, journal of Health Politics, Policy and Law, Medical Care, Milbank Memorial Fund Quarterly/Health and Society, and New England journal of Medicine. IHPS staff have prepared case studies for the Con- gressional Office of Technology Assessment on the cost-effectiveness of upper gastrointes- tinal endoscopy (OTA, 1981a), neonatal in- tensive care (OTA, 1981b), and nurse practi- tioners (OTA, 1981c). IHPS has its own special publications series and periodicals, including the following: · Courses by Newspaper project on "The Nation's Health" included a 15-part series of newspaper articles, a textbook, a study guide, and examination materials. In 1981, the course was presented on a weekly basis in 362 newspapers and 190 colleges and univer- sities in the United States. These materials are to be re-released to newspapers and other institutions which did not carry the project in 1981. · IHPS Report is the IHPS semiannual newsletter, circulated to more than 1,500 in- dividuals and institutions. · HMO Dissemination Project of 1979- 1983 synthesized research findings on the op- erations and performance of HMOs and com- municated these in a series of five regional workshops. · Research Highlights is a quarterly news- letter produced by the IHPS Center for Popu- lation and Health Policy. · Mobius is a quarterly journal (circula- tion 1,000) of continuing education for health science professionals published by the University of California Press. 473 IHPS has sponsored and cosponsored a number of conferences, mostly in California, on a variety of topics including drug regula- tion reform, health insurance reform, cost- benefit and cost-effectiveness methods, high- cost illnesses, caring for the terminally ill, and bioethics. Impact It is difficult to measure directly the im- pact of IHPS activities, because IHPS acts as an analytic and advisory body, as opposed to a policymaking body. Results of health ser- vices research and policy analysis projects have had wide circulation through publica- tion in peer-reviewed journals and are often cited by other investigators. Technical assis- tance and policy analyses provided by IHPS have been used in augmenting and guiding legislative efforts and various policy changes. The primary users of IHPS technical assis- tance (as measured by the volume of requests answered by IMPS) have been Congress and congressional offices, the Executive Office of the President, the Department of Health and Human Services, and the Federal Trade Commission. For these and other federal agencies, IHPS analyses have contributed to research agendas and policy options in such areas as prescription drugs, health man- power, health promotion and disease preven- tion, and health planning and regulation. For instance, in the area of prescription drugs, IHPS contributed to analyses of provi- sions of the Drug Regulation Reform Acts of 1978 and 1979, drug approval processes and drug regulation policies in foreign countries, export of drugs unapproved for use in the United States, generic drugs, drug repackag- ing houses, drug coverage under Medicare and Medicaid, use of drugs by outpatients to minimize hospitalization, physician educa- tion in the area of drug prescription, over- the-counter drugs, federal vaccine and im- munization policies, drug labeling and drug promotion, development of drugs for rare diseases, and drugs and the elderly. For the state of California, IHPS provided analyses of MediCal.reform options, the im- pact of prepaid medical care plans, health and social service policy options in long-term

474 care, the cost-effectiveness of perinatal care, and other areas. The health provider com- munity individual providers, institutions, and service programs have benefited from IHPS technical assistance, information, and educational programs. 'The expansion of IHPS research and analy- sis activities has augmented its role in educa- tion and training. For instance, what began as a small series of weekend workshops in bioethics offered by IHPS has grown into a bioethics teaching program for medical stu- dents and others on the UCSF campus. IHPS faculty have developed some 20 courses in health policy and related areas for students on the UCSF and University of California, Berkeley, campuses. The newly required fourth-year medical school course "Responsi- bilities of Medical Practice," with content in ethical, legal, economic, and social issues, is designed to prompt in medical students a greater awareness of the broad personal and social responsibilities of medical practice and to encourage more responsible and conscien- tious exercise of medical skills. IHPS has been instrumental in several major developments in academic programs at UCSF, including the establishment of the Division of General Internal Medicine; the Division of Medical Ethics; the Aging Health Policy Center; and postgraduate programs in health policy re- search, health policy management, and clini- cal epidemiology. As an Organizational Re- search Unit of the University of California, IHPS has an advisory board that meets peri- odically to review IHPS activities and offer advice on future directions. Reassessment IHPS has not yet reassessed any tech- nology. Funding/Budget The 1985 budget of the IHPS is approxi- mately $2,500,000. Of this amount, about 40 percent is devoted to training fellowships and is funded primarily by foundations. The re- maining 60 percent is devoted to health ser- vices and other technology assessment efforts and is funded by foundations and federal and state governments. ASSESSING MEDICAL TECHNOLOGY Example The following summarizes a recently com- pleted study of changes in the use of medical technologies in hospitals. This work, to be submitted for publication, follows up on a similar study (see I. Showstack et al. t19823~. CHANGES IN THE USE OF MEDICAL TECHNOLOGIES: 1972,1977, 1982 To assess the degree to which the use of medical technologies have changed over time, and the impact of these changes on the costs of medical care, IHPS studied patients admitted to the UCSF hospital over the past decade. Patients discharged during 1972, 1977? or 1982 who had one of the following ten diagnoses were studied: acute asthma, acute myocardial infarction, lung cancer, respiratory distress syndrome of the new- born, cataract excision, delivery (both cesar- ean and vaginal), kidney transplant, stape- dectomy, and total hip replacement. Data were collected from medical and billing re- cords. The principal findings of the study were that the use of older technologies (such as x rays) changed little over the first half of the decade, and length of stay tended to de- crease, while the use of newer diagnostic technologies increased substantially. Later in the decade, some substitution of newer for older technologies was observed. The most cost-increasing changes were the use of sur- gery for certain conditions that would have previously been treated medically and in- creasingly aggressive care for critically ill pa- tients. This project received funding from the Henry I. Kaiser Family Foundation and the National Center for Health Services Re- search. Sources Lee, P. R., Professor of Social Medicine, Institute for Health Policy Studies, University of California, San Francisco. 1984. Personal communication. Office of Technology Assessment. 1981a. The Cost Effectiveness of Upper Gastrointestinal Endoscopy. Case Study #8. Washington, D.C.: U.S. Government Printing Office. Office of Technology Assessment. 1981b. The Costs and Effectiveness of Neonatal Intensive Care. Case

APPENDIX A: PROFILES Study #10. Washington, D.C.: U.S. Government Printing Office. Office of Technology Assessment. 1981c. The Costs and Effectiveness of Nurse Practitioners. Case Study # 16. Washington, D. C.: U. S. Government Printing Office. Showstack, J., Coordinator of Research and Policy Analysis, Institute for Health Policy Studies, Univer- sity of California, San Francisco. 1985. Personal com- munication. 475 Showstack, J. A., S. A. Schroeder, and M. F. Mat- sumoto. 1982. Changes in the use of medical technolo- gies, 1972-1977: A study of 10 inpatient diagnoses. New England Journal of Medicine 306:706-712. University of California, San Francisco Institute for Health Policy Studies, School of Medicine. 1983. Health Services Policy Analysis Center—Final Report submitted to the National Center for Health Services Research.

Cooperative Studies Program Veterans Administration (1511) t310 Vermont Ave., N.W. Washington, DC 20420 (202) 3~39 2861 Major Emphases of Technology Assessment Activities Concerns Technology Drugs Safety Efficacy/ Cost/Cost-Effect/ Effectiveness Cost-Benefit X X X X X X . . . Ethical/Legal/ Social X Medical Devices/Equipment/Supplies Medical/Surgical Procedures Support Systems O rganizational/ Adm inistrative X X Stage of Technologies Assessed X Emerging/new Accepted use Possibly obsolete, outmoded Application of Technologies Prevention X Diagnosis/screening X Treatment Rehabilitation Assessment Methods Laboratory testing X Clinical trials Epidemiological and other observational methods Cost analyses Sim ulation/ modeling Group judgment Expert opinion Literature syntheses Approximate 1985 budget for technology assessment: $12,000,000* * The 1985 budget for the CSP Is approximately $12 million. However, this does not reflect the full cost of the cooperative studies. This amount is primarily for support of the CSP coordinating centers and other nonclinical aspects of the cooperative studies. The clinical cost of these trials is met entirely through VA medical benefits, and is not reflected in the CSP budget. COOPERATIVE STUDIES PROGRAM VETERANS ADMINISTRATION Introduction The Veterans Administration (VA) extends to eligible veterans free or highly subsidized health care services, including hospital, am- bulatory, and nursing home care. The VA provides most of its care at its 172 hospital centers, where it also operates outpatient clinics and 101 nursing home units. In 1983, 476 total medical care outlays for the VA system were $8.3 billion. The VA annually assists about 3 million veteran patients, including about 1.4 million inpatients. The VA has three major research and de- velopment services and several activities ad- dressing technology assessment. The VA de- voted about $164 million in FY 1984 to research arid development activities con- ducted in the Medical Research Service ($148 million), the Rehabilitation Research and

APPENDIX A: PROFILES Development Service ($11 million), and the Health Services Research and Development Service ($5 million). The Rehabilitation Re- search and Development Evaluation Unit evaluates rehabilitative devices arising from VA research and encourages their production and distribution by private industry. The VA Health Services Research and Development Service supports and conducts evaluations of alternative policies and interventions of care. The VA Supply Service evaluates new equip- ment for safety and effectiveness for procure- ment by VA facilities. In 1984, the VA insti- tuted a Technology Assessment Committee to make recommendations to the VA medical director regarding priority technologies for assessment, appropriate assessment methods, and purchasing and deployment of technolo- gies, to track assessment activities of other agencies, and to coordinate these and other agency-wide assessment activities. In 1982 the VA initiated a Prosthetics Technology Evaluation Committee to coordinate the evaluation of VA prosthetic products and de- vices. The VA Cooperative Studies Program (CSP) was established in 1972 in the VA Med- ical Research Service to provide coordination and support for multicenter medical studies that fall within the purview of the Medical Research Service, the Rehabilitation Re- search and Development Service, and the Health Services Research and Development Service. CSP is involved only in trials requir- ing participation of more than one VA medi- cal center. The VA conducts other clinical trials in single centers, and the VA is involved in trials funded by other sources, such as NIH and pharmaceutical companies. The VA spent approximately $20 million on clinical trials in 1984, including $11.3 million for the Cooperative Studies Program. Purpose Cooperative studies enable investigators from two or more VA medical centers to study collectively a selected problem in a uni- form manner, using a common protocol with central coordination. The multicenter approach of the VA coop- 477 erative studies facilitates the accumulation of patient samples that are sufficiently large to provide valid significant findings regarding medical technologies. For medical conditions that are relatively rare, cooperative studies may be the only feasible approach, for other more common conditions, these studies en- able accumulation of data more rapidly by pooling the observations of several facilities. The VA is an especially useful environment for multicenter trials because it has a rela- tively uniform and large patient base under one management. This enables uniformity of research methodology, adherence to com- mon protocols, patient follow-up, and fiscal management of large trials. Of course, the VA is a most appropriate setting for research that addresses medical problems of the vet- eran population. Subjects of Assessment The technologies assessed in the coopera- tive studies are drugs, medical devices, and medical and surgical procedures. These re- flect the medical problems of the veteran population. Of the ongoing and recently completed studies, the greatest number treat cardiovascular diseases. Other important ar- eas are alcohol-related diseases and dental and mental conditions. Other trials treat acute infectious diseases, diabetes, epilepsy, and conditions associated with disabling in- juries. The largest number of studies have tested drug therapies, followed by those test- ing surgical procedures. Most studies have addressed therapeutic technologies, although a few have focused on prevention of cardio- vascular disease through control of hyperten- sion. A total of 81 VA cooperative studies have been conducted since the program's in- ception, including those ongoing in 198S. Ta- ble A-16 lists the subjects of VA cooperative studies. Stage of Diffusion Cooperative studies are generally con- ducted for new technologies that have been subject to preliminary trials in humans.

478 ASSESSING MEDICAL TECHNOLOGY TABLE A-16 Subjects of Veterans Administration Cooperative Studies (listed by status as of January 1985) Studies Approved by Medical Research "Triage" Review and Currently in Active Planning Hepatitis B Vaccine in Patients with Chronic Renal Failure Percutaneous Transluminal Coronary Angioplasty Reflux Esophagitis Complicated by Barrett's Esophagus: A Prospective Randomized Trial of Medical and Surgi- cal Therapies Treatment of Lymphatic Neoplasms Directed by In Vitro Chemo-Sensitivity Testing Toluidine Blue Rinse as a Screening Agent for Detection of Asymptomatic Mucosal Carcinoma A Double Blinded Randomized Comparison of Nitrendipine with a Diuretic or a Beta Blocker in Mild Hyperten- sion Natural History of Bronchitis & Emphysema: Predictive Value of Small Airway Tests & Effect of Smoking Cessa- tion Therapy of Primary Amyloidosis Studies Approved But Not Yet Funded Early Detection of Hearing Loss Due to Ototoxic Agents by High Frequency Auditory Evaluation Decapeptyl in Advanced Prostatic Cancer The Efficacy of Oral Physostigmine in Alzheimer Disease and Senile Dementia of the Alzheimer Type Treatment of Specific Types of Status Epilepticus Vasodilators Used in Chronic Heart Failure-II A Randomized Study of Prostatic Surgery for Benign Prostatic Hyperplasia in Elderly Men Protein-Calorie Therapy in Combination with Anabolic Steroids in Alcoholic Hepatitis-II Primary Treatment of Esophageal Carcinoma Ongoing Cooperative Studies Clinical Evaluation of Two New Dental Alloy Systems Used in the Fabrication of Fixed Crown and Bridge Resto- ration (NIDR-VA) Coronary Artery Surgery I Stable Angina (Vein Bypass) Coronary Artery Surgery II Unstable Angina (Vein Bypass) Dental Implants (Removable vs. Permanent Dentures) Vasodilators Used in Chronic Heart Failure Evaluation of Specific & Cross-Protective Immunity in High Risk (Renal Insufficiency, Alcoholic Hepatic Insuffi- ciency & Elderly) Patients Following Pneumococcal Capsular Polysaccharide Vaccine Percutaneous Transluminal Angioplasty in the Lower Extremity Evaluations of Corticosteroids Therapy in Severe Sepsis Asymptomatic Carotid Stenosis: Etiological Importance in Development of Stroke Randomized Clinical Trial of Total Parenteral Nutrition in Malnourished Surgical Patients Lithium Treatment in Alcohol Dependence Treatment of Depression Collaborative (NIMH-VA) Research Program Prognosis & Outcome Following Heart Valve Replacement (Non-Biological vs. Tissue) Clinical Comparison of Base Metal Alloys vs. a Gold Alloy Used in the Fabrication of Fixed (Crown & Bridge) Restorations Anticoagulants in the Treatment of Cancer Spontaneous Pneumothorax Antiplatelet Therapy After Coronary Bypass Surgery Effects of Reduction in Drugs or Dosage After Long Term Control of Hypertension Treatment of Mild Hypertension in the Aged: Anti-Hypertensive Effectiveness and Patients' Toleration of Differ- ent Regimens Vietnam Experience: Twin Find Study Comparative Efficacy of Vascular Bypass Graft Materials in Lower Extremity Revascularization Clinical Studies of Biphasic Calcium Phosphate Ceramic in Periodontal Osseous Defects Prospective Evaluation of the Efficacy & Tolerance of Oral Trimethoprim Sulfamethoxazole Prophylaxis in Granulocytopenic Patients with Acute Non-Lymphocytic Leukemia Efficacy and Toxicity of Carbamazepine vs. Valproic Acid for Partial Seizures A New Strategy to Preserve the Larynx in Treatment of Advanced Laryugeal Cancer Cooperative Clinical Trial of Sclerotherapy for Esophageal Varices in Alcoholic Liver Disease

APPENDIX A: PROFILES TABLE A-16 Continued 479 Cooperative Studies in Final Analysis Hepatitis and Dentistry Patient Compliance and Its Role in Dental Plaque Control A Comparison of Hospital & Home Treatment Programs for Aphasic Patients Evaluation of Anti-Epileptic Drugs (Phenobarb vs. Phenytoin vs. Primidone vs. Carbamazepine) Drugs & Sleep Phase III—Comparison of Phenobarb & Dalmane in Insomnia EEG Antabuse in Treatment of Alcoholism A Randomized Comparison of the Peritoneo-Venous Shunt (LeVeen) & Conventional Medical Treatment Alone for Ascites in Patients with Alcoholic Cirrhosis The Treatment & Prevention of Infection-Induced Urinary Stones in Spinal Cord Injury Recently Completed Studies Renal Failure Self Care Dialysis (Hemo vs. Peritoneal Dialysis) Nafeillin Therapy of Staphylocoeeal Baeteremia Platelet Aggregation in Diabetes (Use of Aspirin & Persantine) Community vs. VA Nursing Home Care vs. Hospitalization in Psychiatric Patients Alcoholic Hepatitis (Steroid Therapy) Aspirin in Unstable Angina Vasodilators in Acute MI Characteristics of Psychiatric Programs & Their Relationship to Treatment Effectiveness Alcoholic Hepatitis (Steroid Therapy) Bowel Prep for Elective Colon Surgery SOURCE: Veterans Administration (1984~. Concerns The primary concerns of cooperative stud- ies are safety, efficacy, and cost-effective- ness. Although cost-effectiveness is not a con- cern for all studies, it is receiving greater attention, and its appropriateness will be considered for all future studies. Of the 14 studies in active planning (see Table A-16), at least 6 have an explicit cost-effectiveness component, e.g., in studies of hepatitis B vaccine, percutaneous transluminal coronary angioplasty, and continuous peritoneal dialy- sis. At least three ongoing studies have ex- plicit cost-effectiveness components, includ- ing studies of pneumococcal vaccine immunity in high-risk patients, percutaneous transluminal angioplasty in the lower ex- tremities, and parenteral nutrition in mal- nourished surgical patients. Requests The origination, selection, conduct, and reporting of VA cooperative studies follow well-defined guidelines. A cooperative study usually begins with the submission by a VA researcher- physicians and investigators in VA centers around the United States of a planning request, i.e., an initial study pro- posal, to the chief of the Cooperative Studies Program. Recently, the CSP office has begun to encourage studies in certain areas of spe- cial interest to the VA. Selection Planning requests are reviewed by VA pro- gram specialists who provide written cri- tiques and are then evaluated by a Triage Re- view Committee. This committee comprises primarily representatives of the Office of the Associate Chief Medical Director for Re- search and Development, Medical Research Service and Professional Services. They may decide to reject a request, assign a priority rating, or ask for additional information. The requests with a priority rating are put on a waiting list, and those with the highest pri- ority are chosen for planning. At the time that a study is approved for planning, and again when a study is ap-

480 proved for funding, VA medical centers are invited to participate. Medical centers seek- ing to participate are considered based on a number of criteria, including level of inter- est, availability of appropriate staff re- sources, and availability of eligible study pa- tients. A medical center's participation in a CSP is voluntary, but an agreement to partic- ipate means acceptance of the study protocol without change and acceptance of the prac- tices and guidelines of the CSP program. When a study is funded for planning, the principal investigator is notified by the CSP. Biostatisticians and, where appropriate, clin- ical research pharmacists are assigned to the study planning process and the production of a detailed final proposal. The principle inves- tigator is also informed as to which of the four CSP coordinating centers the study has been assigned. The four special centers estab- lished by the VA to support and coordinate the CSP are located at VA medical centers in Hines, Illinois; Palo Alto, California, Perry Point, Maryland; and West Haven, Connect- icut. These provide the biostatistical and data processing support and administrative coordination for the cooperative studies and ensure their compliance with program guide- lines. A CSP clinical research pharmacy coor- dinating center in Albuquerque, New Mex- ico, provides additional support and coordination for those studies involving drugs and devices, such as dispensing and monitor- ing drugs, and liaison with the FDA and pharmaceutical companies. Ethical, scientific, professional, budget- ary, and administrative aspects of the final proposal are evaluated by three groups, a hu- man rights committee, a cooperative studies evaluation committee, and a budget review group, and at least three independent re- viewers who provide written critiques of these same areas. Based on the judgment of these groups, proposed studies may be com- pletely rejected, rejected with recommenda- tions for resubmission, given conditional ap- proval, or given unconditional approval. Process Almost all VA cooperative studies are ran- domized clinical trials. A few have been non- ASSESSING MEDICAL TECHNOLOGY randomized trials and observational studies. Five groups share the responsibility for con- ducting or monitoring a cooperative study: the study group, the executive committee, the operations committee, the CSP coordi- nating center human rights committee, and the cooperative studies evaluation commit- tee. In general, the current schedule of meet- ings for the study group, executive commit- tee, and operations committee consists of an initial meeting for organizational, informa- tional, and training purposes prior to patient intake, a meeting 9 months after the initia- tion of patient intake, and annual meetings thereafter. If drugs or devices used in a study require FDA approval, an investigational new drug application or investigational device exemp- tion must be filed with the FDA before the study can begin. The study group, composed of all partici- pating investigators and permanent consul- tants to the study and chaired by the study chairperson, reviews the progress of the study, discusses problems encountered, and provides suggestions for improving the study. Results of blind data related to study end points are not discussed with this group. The executive committee is the manage- ment group and major decision-making body for the operational aspects of the study. It in- cludes the study chairperson, the study bio- statistician, the clinical research pharmacists, the hearths) of any special central support unitsts), two or three participating investiga- tors, and selected consultants. This committee decides on all changes in the study and on any subprotocols or other use of the study data and on publications of study results, and takes actions on medical centers whose performance is unsatisfactory. As with the study group, the results of the blind portions of the study are not presented to this group. The operations committee usually consists of experts in the subject matter of the study, an independent biostatistician, and other technical or scientific consultants. Nonvoting members include the study chairperson and the study biostatistician. This committee considers from meeting to meeting whether the study should continue, based on study performance, patient accrual, treatment effi-

APPENDIX A: PROFILES cacy, adverse effects, and other factors; as- sesses the performance of each participating center and makes recommendations regarding continuation, termination, or change in sup- port; and reviews and provides recommenda- tions regarding protocol changes. The human rights committee, besides re- viewing the protocol for human rights issues prior to initiating the study, is responsible for ensuring that patients' rights are protected during the course of the study. This commit- tee meets at least once a year for the duration of the study with the operations committee. Each year, the human rights committee con- ducts three site visits to participating medical centers to ensure that the human rights as- pects of the studies are being observed. . . . . All cooperative studies undergo an in- depth review by the cooperative studies eval- uation committee at 3-year intervals during their active phase. Assessors The assessors include physicians and other health care providers, biostatisticians, clini- cal pharmacists, and others noted above. Turnaround The time from submission of a planning re- quest to approval and initiation of formal planning is generally 4 months. Another 12 months are taken between formal planning of a study and its approval and initiation. Once begun, cooperative studies may range from 1 to 8 years. Reporting All VA medical centers conducting medi- cal research must report regularly to the VA Medical Research Service. Summaries of co- operative studies are included in the annual report to Congress of medical research in the VA. Where applicable, sponsors of investiga- tional new drugs and investigational devices are required to submit annual reports to the FDA. The primary means of keeping cooper- ative study participants informed between meetings are study newsletters prepared and issued regularly by the study chairperson and 481 the study biostatistician or by the executive committee. The presentation or publication of data collected by investigators on patients entered into VA cooperative studies is under the con- trol of the study's executive committee. The results of cooperative studies are published in major refereed journals as the New England Journal of Medicine, Circulation, Journal of the American Medical Association, Archives of General Psychiatry, and others. Impact Results from VA cooperative studies have made significant impacts on clinical practice in the VA systems, as well as on clinical prac- tice at large. Among the most significant studies have been those on aspirin therapy of unstable angina, drug treatments for moder- ate and severe hypertension, chemotherapy for schizophrenia, and coronary artery by- pass surgery in chronic stable angina. Reassessment There have been several instances of reas- sessment of drugs, such as reserpine for hy- pertension and the beta-blocker propranolol for hypertension and for angina. These reas- sessments occur when new drugs and/or regi- mens are compared to prevailing treatments in clinical trials. Funding/Budget Although most VA cooperative studies are supported by the Medical Research Service, occasionally studies are funded by other VA sources or by outside sources such as NIH or the pharmaceutical industry. The funding level for each cooperative study is deter- mined by the Budget Review Group. The 1985 budget for the Cooperative Stud- ies Program is approximately $12 million. However, this is deceptively small. These funds are primarily for support of the CSP coordinating centers and other nonpatient care aspects of the cooperative studies. The clinical costs of these trials is met entirely through VA medical benefits, and is not re- flected in the CSP budget.

482 Example On the following pages is a report by the VA Coronary Artery Bypass Surgery Cooper- ative Study Group, published in the New En- gland Journal of Medicine, November 22, 1984, and is reproduced here with permis- sion. Sources Blue Sheet. 1984. VA spending $4.3 million in EY 1984 on prosthetic/amputation R&D. May 30:P&R-8. Hagans, J., Chief, Cooperative Studies Program, Veterans Administration, Washington, D.C. 1984. Personal communication. Huang, P., Staff Assistant, Cooperative Studies Program, Veterans Administration, Washington, D.C. 1985. Personal communication. ASSESSING MEDICAL TECHNOLOGY Congressional Budget Office. 1984. Veterans Ad- ministration Health Care: Planning for Future Years. Washington, I).C. Goldschmidt, P., Director, Health Services Re- search and Development Service, Veterans Adminis- tration, Washington, D.C. 1984. Personal communi- cation. Office of Technology Assessment. 1983. The Im- pact of Randomized Clinical Trials on Health Policy and Medical Practice. Washington, D.C.: U.S. Gov- ernment Printing Office. Veterans Administration. 1983. Administrator of Veterans Affairs Annual Report 1982. Washington, D.C. Veterans Administration. 1983. Guidelines for the Planning and Conduct of Cooperative Studies in the Veterans Administration. Sixth Edition. Washington, r).c. Veterans Administration. 1984. Cooperative Stud- ies Program Status Report. Washington, D.C.

APPENDIX A: PROFILES 483 ELEVEN-YEAR SURVIVAL IN THE VETERANS ADMINISTRATION RANDOMIZED TRIAL OF CORONARY BYPASS SURGERY FOR STABLE ANGINA THE VETERANS ADMINISTRATION CORONARY ARTERY BYPASS SURGERY COOPERATIVE STUDY GROUP Abstract We evaluated long-term survival after coro- nary-artery bypass grafting in 686 patients with stable an- gina who were randomly assigned to medical or surgical treatment at 13 hospitals and followed for an average of 11.2 years. For all patients and for the 595 without left main coronary-artery disease, cumulative survival did not differ significantly at 11 years according to treatment. The 7-year survival rates for all patients were 70 per cent with medical treatment and 77 per cent with surgery (P = 0.043), and the 11-year rates were 57 and 58 per cent, respectively. For patients without left main coronary- artery disease, the 7-year rates were 72 and 77 per cent in medically and surgically treated patients, respectively (P = 0.267), and the 11-year rates were 58 per cent in both groups. A statistically significant difference in survival suggest- ing a benefit from surgical treatment was found in patients without left main coronary-artery disease who were sub- divided into high-risk subgroups defined angiographical- ly, clinically, or by a combination of angiographic and clinical factors: (1) high angiographic risk (three-vessel disease and impaired left ventricular function) at 7 years, 52 per cent in medically treated patients versus 76 per cent in surgically treated patients (P = 0.002); at 11 years, 38 and 50 per cent, respectively (P = 0.026); TN 1975 the Veterans Administration Cooperative 1 Study of Surgery for Coronary Arterial Occlusive Disease first reported a statistically significant surviv- al difference in favor of surgery in the subgroup of patients with left main coronary-artery disease. Two years later, in a preliminary reports on patients with- out disease in the left main artery who were followed for a minimum of 21 months, no significant difference in survival was found between medical and surgical treatment groups either overall or in angiographically defined subgroups. Subsequently, a high-risk sub- group of patients without left main coronary-artery disease, defined on the basis of clinical risk factors alone, was reported to have a significantly reduced five-year cumulative mortality with surgery.3 This report compares 7-year and 1 1-year survival after assignment to medical and surgical treatment in patients who were followed for a minimum of 107 months. Survival results for the entire group as well as for risk groups defined by angiographic and clinical measures are also presented for patients without left main coronary-artery disease. Updated survival re- sults for patients with such disease have been reported previously.4 Report prepared by Katherine M. Detre, M.D., D.P.H., Peter Peduzzi, Ph.D., Timothy Takaro, M.D., Herbert N. Hultgren, M.D., Marvin L. Murphy, M.D., and George Kroncke, M.D. Address repent requests to Dr. Detre at the Veterans Administration Medical Center, West Haven, CI 06516. For a complete listing of participants, members of the Operations and Executive Committees, Coordi- nat~ng Center staff, and consultants, refer to Circulation 1981, 63:1329 (Ap- pendix C). Supported by the Veterans Administration Cooperative Studies Pro- gram, Medical Research Service, Veterans Adminis~anon Central Office, Wash- ington, D.C. (2) clinically defined high risk (at least two of the fol- lowing: resting ST depression, history of myocardial in- farction, or history of hypertension)—at 7 years, 52 per cent in the medical group versus 72 per cent in the surgi- cal group (P = 0.003); at 11 years, 36 versus 49 per cent, respectively (P = 0.015); and (3) combined angiographic and clinical high risk at 7 years, 36 per cent in the medical group versus 76 per cent in the surgical group (P = 0.002); at 11 years, 24 versus 54 per cent, respec- tively (P = 0.005). Survival among patients with impaired left ventricular function differed significantly at 7 years (63 per cent in the medical group versus 74 per cent in the surgical group [P = 0.049]) but not at 11 years (49 versus 53 per cent). The surgical treatment policy resulted in a nonsignifi- cant survival disadvantage throughout the 11 years in sub- groups with normal left ventricular function, low angio- graphic risk, and low clinical risk, and a statistically significant disadvantage at 11 years in patients with two- vessel disease. We conclude that among patients with stable ischemic heart disease, those with a high risk of dying benefit from surgical treatment, but beyond seven years the sur- vival benefit gradually diminishes. (N Engl J Med 1984; 311 :1333-9.) METHODS The Veterans Administration cooperative study of coronary-ar- tery bypass grafting is a randomized controlled trial of medical therapy versus medical plus surgical therapy for the treatment of patients with stable angina pectoris and angiographically confirmed coronary-artery disease. The study design, entry criteria, and base- line characteristics of the patient population have been described previously.S Briefly, between 1972 and 1974, 686 patients with sta- ble angina pectoris of more than six months' duration who had been receiving medical therapy for three months and who had resting or exercise electrocardiographic evidence of myocardial ischemia were randomly assigned to medical or surgical therapy. Patients were excluded from randomization if they had had a myocardial infarc- tion within six months or if they had refractory systemic diastolic hypertension (>100 mm Hg), left ventricular aneurysm or other serious cardiac disease, other organ-system disease making surgery inadvisable or limiting life expectancy to less than five years, unsta- ble angina, or uncompensated congestive heart failure. In the 1972-1974 cohort, 354 patients were randomly assigned to medical therapy, and 332 to surgical therapy, at a total of 13 clinical sites. The base-line distribution of risk factors (history, angiograph- ic findings, electrocardiographic findings, and severity of angina) was comparable in the two treatment groups.6 Twenty patients randomly assigned to bypass surgery did not have an operation. Ninety-four per cent of those who underwent surgery did so within three months after random assignment. The average number of diseased vessels in surgically treated patients was 2.4, and the average number of grafts placed was 2.0. All 45 patients with single-vessel disease received at least one graft, and one fourth received multiple grafts. Of the 102 patients with two- vessel disease, 80 per cent received two or more grafts. Of the 163 patients with triple-vessel disease, 90 per cent received two or more grafts, and 37 per cent received three or more. The overall 30-day operative mortality rate was 5.8 per cent. The incidence of perioperative myocardial infarction, calculated on the basis of the development of new Q waves, was 9.9 per cent. Vein- graft angiography was performed in 79 per cent of surgical patients (247 of 312) between 10 and 15 months after surgery, and 353 of 503 grafts placed (70 per cent) were patent at one year; 87 per cent of

484 ASSESSING MEDICAL TECHNOLOGY patients (214 of 247) had at least one patent graft. Five years after random assignment, 52 of the 312 patients had died, and 9 had had a second operation. Graft angiography was done at five years in 156 of the 251 remaining eligible patients (62 per cent), and the patency rate was 67 per cent. The one-year and five-year graft-patency rates for the 143 patients evaluated at both times were 74 and 67 per cent, respectively. Of 354 patients randomly assigned to medical treatment, l 33 (38 per cent) had bypass surgery during an average follow-up of 11.2 years. Of the 133, 22 had left main coronary-artery disease and crossed over to surgery on an elective basis in accordance with a protocol amendment.7 8 Thirty-five ( l l per cent) of the 312 patients randomly assigned to surgery who had coronary-artery bypass grafting have had repeat grafting. Medical therapy consisted of nitrates, beta-blockers, and other medications administered to achieve symptomatic relief of angina. At one year, 26 per cent of medically treated patients were taking nitroglycerin or nitrates only, 3 per cent were using propranolol only, and 65 per cent were taking both types of medication. The corresponding rates at five years were 27, 4, and 57 per cent. At one year and five years, 6 and 12 per cent of patients, respectively, were not taking any medication. The surgical patients took less medica- tion than the medical patients, but their use of medication increased between one and five years. At one year, 42 per cent took no medica- tion, 45 per cent were taking nitroglycerin or nitrates only, and the remaining 13 per cent were taking both types of medication. The corresponding rates at five years were 25, 36, and 36 per cent. At five years 3 per cent of surgical patients were taking propranolol alone. The average follow-up time was calculated as the average time from the date of random assignment to the date of the analysis. Included in the calculation were patients who died and those known to be alive but without current follow-up data except for survival status. Cumulative survival rates were determined by the actuarial life- table method, with death from all causes used as the end point. The survival status for patients who did not return for scheduled follow- up visits was ascertained by a retrieval system known as BIRLS (Beneficiary Identification and Records Locator Subsystem, Austin Tex.), which is unique to the Veterans Administration network. Telephone contact was used in the few cases in which BIRLS had no patient record. The survival status was known for all but one pa- tient. At present, 99.9 per cent of study patients have completed 9 years of follow-up, 91 per cent have com- pleted 10 years, and 73 per cent have com- pleted 11 years. Life-table cumulative sur- vival rates were calculated according to the original treatment assignment (treatment policy) from the date of randomization. Dif- ferences in cumulative survival between the p=.124 p=.043 p=.45 p=.527 p=.267 p=.813 two treatment groups were assessed by the Mantel-Haenszel test. Thus, the 7-year sta- 1.00 fistic represents the cumulative survival ex- ~ ~ ~~ perience up to 7 years, and the 11-year sta- A 90 - _ 83 - ~ .82 talc represents the cumulative experience > .80 ~'~ _ 77 - ~ .77 up to 1 1 years. All P values reported are two- > 78~ ~ .80 ` tailed and uncorrected for multiple compar- ~ 70 ~ ~~ - - 72'~'-~~ isons. z .60 `%o. 58 ~8 _ In addition to the overall treatment re- O 57 .58 suits, survival was compared in angiographi- ~ 50 cally and clinically defined subgroups of 0 .40 - patients without left main coronary-artery ~ disease. The angiographically defined sub- ~ 30 groups were identified on the basis of the ~ .20 ~ ·SURGICAL · ·SURGICAL number of vessels diseased (one, two, or >-—~ MEDICAL on oMEDICAL three) and left ventricular function. The .10 - 332 S 479 S - - 284 S ,52 S presence or absence of left ventricular func- 354 M ~ 84 M 34 ~ M ~ 68 M tional impairment was determined accord- ing to a central reading of base-line left ventriculograms performed at the Seattle Veterans Administration Medical Center under the supervision of Dr. Karl Hammer- meister. Global ejection fractions and seg- mental contraction abnormalities were measured. Contraction abnormalities were graded as follows: 1, no abnormality; 2, minimal hypokinesis or akinesis involving less than 25 per cent of the heart border; 3, moderate hypokinesis or alcinesis of 23 to 75 per cent of the heart border; 4, dyskinesia, left ventricular aneurysm, or paradoxical wall motion; and 5, severe generalized hypokinesis or akinesis of the entire heart border. Left ventricular function was considered to be impaired if the global ejection fraction was less than 50 per cent or if the contraction grade was over 2; otherwise, left ventricular function was defined as normal. By this definition, 55 per cent of the patients had impaired function. In previous reports-5 9 left ventricular function was defined as abnor- mal if there was cardiac enlargement, elevated end-diastolic pres- sure (>14 mm Hg), an ejection fraction under 45 per cent, or any degree of contraction abnormality, as evaluated by the individual participants. Central readings on left ventriculograms were done in 75 per cent of the patients. Base-line readings by the individual clinics were used to provide data on left ventricular function in the other patients, according to the new definition. The combination of three-vessel disease and impaired left ventricular function was clas- sified as a high angiographic risk. All other combinations of one-, two-, or three-vessel disease and normal or impaired left ventricular function constituted a low angiographic risk. Subgroups with a low, middle, or high clinical risk were defined on the basis of a multivariate risk function in order to predict five- year mortality,3 ~° using four established clinical-risk variables measured at base line: the New York Heart Association classifica- tion, a history of hypertension, a history of myocardial infarction, and an ST-segment depression on the resting electrocardiogram. Other risk factors, which were not uniformly measured in all pa- tients at base line (e.g., positive exercise test) or which had a low prevalence in the study population (e.g., congestive heart failure), could not be considered for inclusion in this risk function. Patients in the low-risk subgroup included those with none or only one of the four risk factors except for ST depression. The high-risk subgroup consisted of patients with combinations of two or three of the strong- est predictors (ST depression, a history of myocardial infarction and a history of hypertension)—i.e., those with multiple clinical risk factors. The validity of this method for the classification of patients into clinical-risk groups has been established in an inde- pendent population.~° Reviewers and others ~2 have criticized such "post hoc" subgroups. However, the original protocol for the 1972-1974 Veterans Administration study clearly outlined the ana- CUMULATIVE SURVIVAL RATES ALL HOSPITALS ALL PATIENTS ALL NON-LMD .00 .90 80 70 .60 .50 .40 .30 .20 .10 1 2 3 4 5 6 i 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11 YEAR Figure 1. Eleven-Year Cumulative Survival for All Patients and for Those without Left Main Coronary-Artery Disease (non-LMD), According to Treatment Assignment. Numbers of patients at risk are given at bottom of figure. M denotes medical, and S surgical.

APPENDIX A: PROFILES 1yncal steps for development of both the ang~ographic- and clinical- nsk groups: "Regression analyses will be used to determine the effect [of base-line variables] on mortality and to determine groups with low and high mortality Ask.... Analyses [life table] will be done for patients in low and high risk groups." Thus, the clinical- nsk groups, defined by noninvasive base-line measures, were nei- ther more nor less post hoc than the ang~ographic-nsk groups, de- fined by such factors as left main coronary-artery disease or the combination of vessel disease and left ventricular function. Survival analyses are based on data from all 13 hospitals, by treatment policy. In the Results we focus on the 7-year and 11-year cumulative survival rates. The five-year survival rates (early expe- r~ence) are shown in the figures but are not discussed in the text, except in comparing this study with the European and the Nanona1 Heart, Lung, and Blood Institute studies. All treatment comparisons are presented in reference to the medical treatment policy. RESULTS Cumulative survival rates are shown in Figures 1 through 5. Patients with left main coronary-artery dis- ease are excluded from the subgroup analyses shown in Figures 2 through 5. Overall Results Overall, excluding patients with left main coronary- artery disease, the treatment difference was not signifi- cant at seven years (72 per cent in the medical group versus 77 per cent in the surgical group, P = 0.267; Fig. 1~. The medical and surgical survival curves con- verge when follow-up data are extended to 11 years (58 per cent in both groups, P = 0.813~. During the first 7 years of follow-up the average annual mortality rates were 4.0 per cent for medical therapy and 3.3 per 1.00 .90 ,>, .80 is, . 70 CO z .60 i_ .50 O .40 O .30 .20 .10 485 cent for surgery, including operative mortality, as compared with 3.5 and 4.8 per cent, respectively, be- tween 7 and 1 1 years. If patients with left main coronary-artery disease are included, the trends are similar, although the treatment difference in all patients was statistically significant at 7 but not at 11 years. Vessel Disease There was a nonsignificant trend toward improved survival with surgery at seven years in the subgroup of patients with three-vessel disease: 63 per cent with medical treatment vs. 75 per cent with surgical treat- ment, P—0.061 (Fig. 2~. The difference in the cumu- lative survival rates diminished after 7 years, resulting in only a 6 per cent difference at 11 years. At 7 years neither patients with single-vessel disease nor those with double-vessel disease had a significant difference in survival associated with treatment, although at 11 years surgically treated patients with two-vessel dis- ease had a marginally significant disadvantage in sur- vival (P = 0.045). Left Ventricular Function At 7 but not at 11 years, there was a significant difference in survival between medically and surgical- ly treated patients with impaired left ventricular func- tion (63 vs. 74 per cent, respectively; P = 0.049); sur- vival rates at 11 years were 49 and 53 per cent, respectively (P = 0.249, Fig. 3~. Among patients with normal left ventricular function, survival was 84 per CUMULATIVE SURVIVAL RATES ALL HOSPITALS 1 VESSEL DISEASE 2 VESSEL DISEASE 3 VESSEL DISEASE I I I I 1 1 1 1 1 1 1 _' ~ ~ ~ ~ ~ ~ I 1 1 1 I I I I 1 1 1 p= 291 p= 522 p= 589 p= 267 p= 213 p= 045 p= 305 p= 061 p= 16 ·~-~z p..9 9'S7~3 .. I ~ ·SURGICAL ~ ·SURGICAL · ·SURGICAL ~ oMEDlcAL of oMEDlcAL of o MEDICAL 1 - 49 S 31 S - - 98 S 49 S - - 135 S 70 S - 48 M 30 M 105 M 67 M 156 M 71 M ~ I ~ 1. 1 1 1 ~ I I I ~ 1 1 1 1 1 1 1 1 1 1 1 1 2 3 4 5 6 7 8 9 1011 1 2 3 4 5 6 7 8 9 1011 1 2 3 4 5 6 7 8 9 1011 YEAR Figure 2. Eleven-Year Cumulative Survival for Patients without Left Main Coronary-Artery Disease Who Had Single-, Double-, or Triple-Vessel Disease. Numbers of patients at risk are given at bottom of figure. M denotes medical, and S surgical.

486 1.00t oz to } .80 ~ .70 _ an z .60 O- .50 G O .40 _ O .30 .20 _ 10 IMPAIRED LVF p= 130 p= 049 63~—>~53 . 49 SURGICAL -~oMEDICAL CUMULATIVE SURVIVAL RATES ALL HOSPITALS l p= .249 _ - 150S 77S 1 75 M 79 M 1 NORMAL LVF p= 229 p=.350 p= 249 84 85 ~~ ~71 64 _ - ~ ·SURGICAL on-—"oMEDICAL 133 S 74 S - 135 M 88 M I 1 1 1 1 1 1 1 1 1 1 I I ~ 1 1 1 1 1 1 1 1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11 YEAR Figure 3. Eleven-Year Cumulative Survival for Patients without Left Main Coro- nary-Arte~ Disease, According to Whether Left Ventricular Function (LVF) Was Im- paired or Normal. Numbers of patients at risk are given at bottom of figure. M denotes medical, and S surgical. cent in the medical group and 80 per cent in the surgical group at 7 years, and 71 and 64 per cent, respectively, at 11 years. These differences were not . . s~gn~hcant. Risk Analysis There was a statistically significant improvement in survival at seven years in surgically treated patients with a high angiographic risk (three-vessel disease with impaired left ventricular func- tion); the rates were 52 per cent for medical treatment versus 76 per cent for surgical treatment (P = 0.002, Fig. 4~. Although from 7 to 11 years, the marked difference in survival rates diminished from 24 to 12 per cent, the difference in cumulative survival up to 11 years remained significant (P= 0.026~. In contrast, by 11 years, patients with a low angiographic risk had a survival rate of 68 per cent with medical therapy and 61 per cent with surgery (P = 0.105~. The Veterans Administration study reported a significant surviv- al benefit with surgery at five years in patients with a high clinical risk and a significant benefit with medi- cal therapy in patients at low risky The seven-year survival rates in the high-risk tercile were 52 per cent for the medical group and 72 per cent for the surgical group (P = 0.003, Fig. 5). Beyond seven years, surviv- 1 00 \ .80 ~ .70 U) id o - o o .60 .50 .40 .30 at ASSESSING MEDICAL TECHNOLOGY al remained higher in the surgical group, but the difference gradually diminished from 20 to 13 per cent by 11 years. The cumulative surviv- al experience up to 11 years differed significantly between the two treat- ment groups (P = 0.015~. In con- trast, for patients in the low-risk tercile there was a 7 per cent surviv- al disadvantage with surgical ther- apy at seven years (88 per cent in the medical group vs. 81 per cent in the surgical group, P = 0.093), which increased to 10 per cent at 1 1 years (73 per cent in the medical group vs. 63 per cent in the surgical group, P= 0.066~. In the middle- risk tercile, there was no significant difference in survival at any time. When survival in the subgroup of patients with a high angiographic risk was studied separately in the patients at low, middle, and high clinical risk, a statistically signifi- cant surgical benefit was observed only in patients who were at high risk not only angio- graphically but also clinically (Table 1~. No signifi- cant difference in survival was observed in patients with a high angiographic risk who had a low or middle clinical risk. Although the survival experience was sim- ilar in all clinical-risk subgroups of surgically treated patients with a high angiographic risk, survival in medi- cally treated patients decreased with increasing clini- cal risk at both 7 and 11 years, reflecting the strong CUMULATIVE SURVIVAL RATES ALL HOSPITALS ANGIOGRAPHIC HIGH RISK ANGIOGRAPHIC LOW RISK l l l 4 p = 018 p= 002 p= 026 1 - - 3 ) - Abe `~ N ok" ~50 52' - ~` 38 ~ · ·SURGICAL .__ on oMEDlcAL .10 - 71 S 97 M 1 1 1 1 1 1 1 1 ~ 1 ~ 1 2 3 4 5 6 7 8 9 10 11 p= 156 p= 156 p= 105 O W_~ ~ 35 S 35 M · · SU RG I CAL °~ °MEDICAL - 210 S 114 S - 211 M 132M _ 1 1 1 1 1 1 1 1 1 1 1 2 3 4 5 6 7 8 9 10 11 YEAR Figure 4. Eleven-Year Cumulative Survival for Patients without Left Main Coronary- Artery Disease, According to Angiographic Risk. High risk was defined as three-vessel disease plus impaired left ventricular function, and low risk as one-, two-, or three-vessel disease plus normal left ventricular function or one- or two-vessel disease plus impaired left ventricular function. Numbers of patients at risk are given at bottom of figure. M denotes medical, and S surgical.

APPENDIX A: PROFILES additional effect of clinical risk factors on the natural history of patients with a high angiographic risk. Conversely, when survival in patients with a low angiographic risk was studied separately in the three clinical risk groups (Table 1), a disadvantage with surgery was observed at 7 and 11 years in patients who were at low risk by both measures; however, the differences were not significant. Again, the strong ef- fect of the clinical risk factors on the natural history was evident. Left Main Coronary-Artery Disease The mortality rate for 48 patients with left main coronary-artery disease who were randomly assigned to surgical treatment increased after the seventh year of follow-up (data not shown). During the first seven years, the average annual mortality rate was approxi- mately 3 per cent; thereafter, the rate increased to nearly 5 per cent. Comparison with the assigned medi- cal group was futile, since 47 per cent of the original medical group crossed over and 44 per cent died, leav- ing only four patients with the original treatment as- signment at seven years. DISCUSSION Current survival results by treatment policy for all 13 hospitals with an operative mortality rate of 5.8 per cent (Fig. 1 ) indicate that for all patients and for those without left main coronary-artery disease, the cumula- tive survival experience up to 11 years did not differ significantly (at a two-tailed alpha level of 5 per cent) between medical and surgical treatment groups. 1.00 .10 487 This overall result disregards the heterogeneous natural history of the subgroups. Consistent with the hypothesis that surgery could be advantageous for pa- tients whose natural history was expected to be poor but would offer little or no advantage for those with a good prognosis, we found a range of treatment effects in subgroups, from a significant advantage to a bor- derline or nonsignificant advantage and even a disad- vantage, with surgical therapy. In particular, the small group of patients who were at high risk both an- giographically and by noninvasive clinical risk meas- ures derived the greatest survival benefit from surgery (Table 1), second only to the benefit in patients with left main coronary-artery disease reported previous- ly. l'4 A statistically significant difference was also found when subgroups were defined by angiographic predictors alone i.e., three-vessel disease and mod- erate to severe impairment of left ventricular function (Fig. 4) or by the high-clinical-risk measure alone (Fig. 5~. The surgical benefit was not significant at 11 vears in the subgroups with three-vessel disease alone (Fig. 2) or with moderate to severe impairment of left ventricular function (Fig. 3), although a bene- fit of borderline significance appeared at 7 years (P = 0.061 and 0.049, respectively). At the other end of the spectrum were the subgroups of patients with a good prognosis: those with one- or two-vessel disease (Fig. 2), normal left ventricular function (Fig. 3), a low angiographic risk (Fig. 4), and a low clinical risk (Fig. 5~. With the exception of the group with two-vessel disease, for which the surgical survival rate was significantly worse (P = 0.045), the CUMULATIVE SURVIVAL RATES ALL HOSPITALS H I GH RISK TERCILE MID RISK TERCILE LOW RISK TERCILE l l l l l l l ~ l l l l l l l ,,,,,,,,, r, p=.0006 p=.003 p=.015 p=.818 p=.34s p=.737 p=.012 p=.093 p=.066 ~90 ~04~ ~ `~37 ~7'~ O .30 .36 _ 20 ~ ·SURGICAL ~ ·SURGICAL —-- ·SURGICAL _ °~ °MEDICAL on °MEDICAL on °MEDICAL - 83 S 37 S - - 84 S 48 S - - 113 S 66 S - 94 M 33 M 91 M 53 M 123 M 81 M I I 1 1 1 1 1 1 1 1 1 l l ~ I I I I I I I I I 1 1 1 2 3 4 5 6 7 8 9 1011 1 2 3 4 5 6 7 8 91011 1 2 3 4 5 6 7 8 9 1011 YEAR Figure 5. Eleven-Year Cumulative Survival for Patients without Left Main Coronary-Artery Disease, According to Clinical Risk. See text for definitions of high, middle, and low clinical risk. Numbers of patients at risk are given at bottom of figure. M denotes medical, and S surgical.

488 Table 1. Cumulative Survival Rates at 7 and 11 Years In Patients without Left Main Coronary-Artery Disease, According to Angio- graphic and Clinical Risk.* 7-YEAR RATE (%) 1 I-YEAR RATE (%) NO. MED t SURG t P MED t SURG t P rare +S.E. rare +S.E. High sagiographic risk High clinical risk 67 36+7 76+9 0.002 24+7 54+10 0.005 Middle clinical risk 49 SO+9 79+9 0.069 40+9 i3+13 0.345 50 79+8 77+8 0.818 62+10 52+10 0.586 Low clinical risk Low ang~ographic risk High clinical risk 108 67+7 70+6 0.531 46+7 46+7 0.732 Middle clinical risk 124 82+5 78+5 0.569 73+6 68+6 0.521 Low clinical risk 184 90+3 81+4 0.079 76+5 66+5 0.092 *A total of 13 pacts could not be classified: 4 had missing data for the number of diseased vessels, 2 for Ich ventricular function, and 7 for the cl~nical-nsk subgroup. tMed denotes medical group, and Surg surgical group. 11-year survival disadvantage with surgical treatment was not statistically significant in the low-risk sub- groups. The small survival disadvantage with surgery in these subgroups can probably be explained by the initial mortality associated with surgery. Although the individual subgroup results reported here are weakened by the multiplicity of comparisons and the loss of power in some strata with small num- bers of patients, the survival differences during the first seven years can generally be characterized by what is known about the natural history of chronic stable angina. Depending on the presence or absence of known prognostic indicators, the seven-year cumu- lative mortality in the medical cohort varied widely, from 10 to 64 per cent, yet mortality in the surgical cohort ranged only from 12 to 30 per cent. This result- ed in a significant reduction of mortality for surgically treated patients with combinations of risk factors. Two other large-scale randomized studies of coro- nary-artery bypass grafting have reported survival re- sults: the European Coronary Surgery Studyi3 and the National Heart, Lung, and Blood Institute's Coronary Artery Surgery Study (CASS).~4 Comparison of the three studies is difficult, because each enrolled differ- ent types of patients, and the periods of patient enroll- ment were different. For example, unlike the Veterans Administration study, CASS did not enroll patients with serious left main coronary-artery disease or with severe angina,~4 and the European study did not en- roll patients with an ejection fraction under 50 per cent or with single-vessel disease.~3 Probably in part because of differences in patient characteristics and in part because of improvement in both therapies, the five-year survival rates in medi- cally and surgically treated patients without left main coronary-artery disease differed among the three stud- ies. For medically treated patients the rates were 80 per cent in the Veterans Administration study, 85 per cent in the European study (calculated from reported data'3), and 92 per cent in CASS; for sur- gically treated patients the rates were 82, 93 (cal- ASSESSING MEDICAL TECHNOLOGY culated from reported data~3), and 95 per cent, respec- tively. The corresponding percentage reductions in overall mortality for the surgical group as compared with the medical group were 10 per cent in the Veter- ans Administration study, 53 per cent in the European study, and 38 per cent in CASS. Neither the Veterans Administration result nor the CASS result was statis- tically significant. The subgroups with the largest benefit from surgi- cal treatment in the Veterans Administration study have no direct counterparts in the other two studies. The subgroup of patients in CASS that resembles most closely the Veterans Administration high-angio- graphic-risk group, the subgroup with three-vessel disease and an ejection fraction under 50 per cent, had a nearly significant benefit from surgery at five years (P = 0.063~. On the other hand, the European study, which examined the joint effect of clinical and angio- graphic risk factors, concluded that "in the absence of "clinically defined] prognostic variables in patients with either two- or three-vessel disease the outlook is so good that early surgery is unlikely to increase the prospect of survival." Thus, all three studies point toward a possible surgical benefit in the presence of high risk i.e., multiple risk factors that indicate a poor prognosis measured by angiography or by other means. With data now available from the extended follow- up in the Veterans Administration study, long-term results of therapy can be studied. So far the most , important observation is that the mortality rate in all surgical subgroups increased between 7 and 11 years. During the first seven years of follow-up, the average annual mortality rate was 3.3 per cent for all surgi- cally treated patients without left main coronary-ar- tery disease, as compared with a rate of 4.8 per cent during the next four years. For medically treated pa- tients without left main coronary-artery disease, the rates were 4.0 and 3.5 per cent, respectively. The in- creased mortality in the surgical group is consistent with the findings of the Montreal Heart Institute in- vestigators who followed a series of patients for 12 years. They found that although angina had improved in 80 per cent of patients at 6 years, it remained improved in only 47 per cent of the 12-year survi- vors. '5 The annual graft-closure rate at 7 to 12 years was 5.2 per cent more than double the 2.1 per cent rate between 1 and 7 years. The Montreal Heart Institute predicted that because of late graft changes, long-term relief of symptoms and survival may be compromised. Our observation of accelerated mortality after seven years in surgically treated pa- tients but not in those receiving medical treatment supports this prediction. In conclusion, we found that in the Veterans Ad- ministration study population bypass surgery did not significantly improve overall survival among patients without left main coronary-artery disease. However, a survival benefit with surgery was observed at five to seven years in subgroups of patients with multiple

APPENDIX A: PROFILES clinical and angiographic risk factors. The observed benefit with surgery diminished gradually when fol- low-up was extended to 11 years. REFERENCES 1. 489 7. Takaro T. Hultgren HN, Lipton MJ, Detre KM, et al. The VA Cooperative Randomized Study of Surgery for Coronary Arterial Occlusive Disease. II. Subgroup with significant left main lesions. Circulation 1976; S4: Suppl 3:III-107-17. 2. Murphy ML, Hultgren HN, Detre K, Thomsen J. Talcaro T. et al. Treatment of chronic stable angina: a preliminary report of survival data of the random- ized Veterans Administration cooperative study. N Engl J Med 1977; 297:621-7. 3. Detre K, Peduzzi P. Murphy M, et al. Effect of bypass surgery on sur- vival of patients in low- and high-risk subgroups delineated by the use of simple clinical variables: Veterans Administration Cooperative Study of Surgery for Coronary Arterial Occlusive Disease. Circulation 1981; 63: 1329-38. 4. Takaro T. Peduzzi P. Detre KM, et al. Survival in subgroups of patients with left main coronary artery disease. Circulation 1982; 66:14-22. S. Detre KM, Hultgren HN, Takaro T. et al. Veterans Administration Cooper- ative Study of Surgery for Coronary Arterial Occlusive Disease. III. Meth- ods and baseline characteristics, including experience with medical treat- ment. Am J Cardiol 1977; 40:212-25. 6. Takaro T. Hultgren HN, Detre KM, Peduzzi P. Murphy M. Results of the VA randomized study of medical and surgical management of angina pec- toris. In: Hammermeister KE, ed. Coronary bypass surgery: the late results. New York: Praeger, 1983:19. Detre K, Peduzzi P. The problem of attributing deaths of nonadherers: the VA coronary bypass experience. Controlled Clin Trials 1982; 3:355~4. 8. Parisi AF, Peduzzi P. Detre K, Shugoll G. Hultgren HN, Talcaro T. Character- istics and outcome of medical Is in the Veterans Adminimabon Costive Study of Coronary Artery Surgery. Am J Cardiol 1984; 53:23-8. 9. Talcaro T. Hultgren HN, Detre KM, Peduzzi P. The Veterans Admin~stra- tion Cooperative Study of stable angina: current status. Circulation 1982; 65: Suppl 2:II~7. 10. Peduzzi PN, Detre KM, Chan YK, Oberman A, Cutter GR. Validation of a risk function to predict mortality in a VA population with coronary artery disease. Controlled Clin Trials 1982; 3:47 60. I 1. Braunwald E. Effects of coronary-artery bypass goofing on survival: impli- cations of the randomized coronary-artery surgery study. N Engl J Med 13. 1983; 309:1181-4. 12. Idem. The treatment of coronary artery disease: lessons from clinical trials. Presented at the f~fty-sixth annual meeting of the American Heart Associ- ation, Anaheim, Calif., November 16, 1983. European Coronary Surgery Study Group. Long-tenn results of a prospec- tive randomised study of coronary artery bypass surgery in stable angina pectoris. Lancet 1982; 2:1173-80. 14. CASS Principal Investigators. Coronary Artery Surgery Study (CASS): a randomized trial of coronary artery bypass surgery: survival data. Circula- 15. 16. don 1983; 68:939-50. Enjalbert M, Vaislic C, Ignorance J. Grondin CM, Bourassa MG, Cam- peau L. Relief of angina and survival 12 years after XOrtocoronary saphe- nous vein graft bypass surgery. Circulation 1983; 68: Suppl 3 m-116. ab- stract. Campeau L, Enjalbert M, Vance J. Va~slic C, Grondin CM, Bou~assa MG. Atherosclerosis and late closure of XOrtocoronary saphenous vein grafts: sequential angiog~aphic studies at 2 weeks, 1 year, 5 to 7 years, and 10 to 12 years after surgery. Circulation 1983; 68: Suppl 2:II-1-7. Reprinted from The New England Journal of Medicine 311:1333-1339 (November 22), 1984 ~Copyright, 1984, by the Massachusetts Medical Society Printed in the U.S.A.

Next: Appendix B: Selected Papers »
Assessing Medical Technologies Get This Book
×
Buy Hardback | $90.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

New drugs, new devices, improved surgical techniques, and innovative diagnostic procedures and equipment emerge rapidly. But development of these technologies has outpaced evaluation of their safety, efficacy, cost-effectiveness, and ethical and social consequences. This volume, which is "strongly recommended" by The New England Journal of Medicine "to all those interested in the future of the practice of medicine," examines how new discoveries can be translated into better care, and how the current system's inefficiencies prevent effective health care delivery. In addition, the book offers detailed profiles of 20 organizations currently involved in medical technology assessment, and proposes ways to organize U.S. efforts and create a coordinated national system for evaluating new medical treatments and technology.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!