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First Printing, October 1992
Second Printing, March 1993
Committee to Study the Use of Advisory Committees by the Food and Drug Administration
LAURENCE E. EARLEY,* Chair, Francis C. Wood Professor of Medicine,
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
ROBERT S. ADLER, Associate Professor of Legal Studies,
Graduate School of Business Administration, University of North Carolina, Chapel Hill, North Carolina
RICHARD A. BERMAN,* President,
Howe Lewis International, New York, New York
RICHARD E. CLARK, Professor of Surgery,
Allegheny General Hospital, Pittsburgh, Pennsylvania
DEBORAH COTTON,
Harvard University School of Public Health, Boston, Massachusetts
J. RICHARD CROUT, President,
Boehringer Mannheim Pharmaceuticals, Rockville, Maryland
CAROLYNE K. DAVIS,* National and International Health Care Advisor,
Ernst & Young, Washington, D.C.
JORDAN U. GUTTERMAN, Professor and Chairman,
Department of Clinical Immunology and Biological Therapy, M.D. Anderson Cancer Center, Houston, Texas
SHEILA JASANOFF, Professor and Chair,
Department of Science and Technology Studies, Cornell University, Ithaca, New York
PAUL MEIER,* Professor of Statistics,
University of Chicago, Chicago, Illinois
THOMAS C. MERIGAN, JR.,* Becker Professor of Medicine and Head,
Division of Infectious Disease, Stanford University School of Medicine, Stanford, California
RICHARD A. MERRILL,* Daniel Caplin Professor of Law,
University of Virginia School of Law, Charlottesville, Virginia
HARRY M. MEYER, JR., President,
Medical Research Division, American Cyanamid Company, Pearl River, New York
FRANK E. SAMUEL, JR.,
Government Strategy Associates, Washington, D.C.
LOUIS E. UNDERWOOD, Professor of Pediatrics,
University of North Carolina, Chapel Hill, North Carolina
ALBERT P. WILLIAMS,
The RAND Corporation, Santa Monica, California
JAMES B. WYNGAARDEN,* Associate Vice Chancellor for Health Affairs,
Duke University, and Foreign Secretary, National Academy of Sciences and Institute of Medicine, Washington, D.C.
Study Staff
RICHARD A. RETTIG, Study Director
STANLEY W. AMMONS, JR. Program Officer
HOLLY DAWKINS, Research Assistant
THELMA L. COX, Project Assistant
NANCY DIENER, Financial Associate
RUTH ELLEN BULGER, Director, Division of Health Sciences Policy
Preface
The departments and agencies of the federal government, especially those deeply engaged in scientific and technological matters, have made extensive use of external advisory committees as a means to acquire independent scientific and technical advice. This use of advisory committees has received attention over time from a number of sources, including the Congress, and in recent years has been the subject of more general analytic treatment.1,2
The Food and Drug Administration (FDA) of the Department of Health and Human Services makes extensive use of technical advisory committees. It does so primarily in the support of its evaluation and regulation of drugs, biologics, and medical devices for human use. In 1991, prompted by the Commissioner of Food and Drugs, Dr. David A. Kessler, the FDA requested that the Institute of Medicine (IOM) examine the optimal use of FDA's advisory committees in product evaluation and in relation to agency management and agency accountability. This report results from the deliberations of a committee convened by the IOM to conduct this study.
In general, advisory committees are the major way by which the FDA obtains independent technical and scientific advice, although workshops, symposia, consultants, and extensive, often informal, contacts between agency professionals and the scientific and medical communities are other important means for doing so. Although this report focuses on advisory committees, the IOM committee recognizes and endorses the use of these other means of obtaining independent expert advice.
The FDA advisory committee system was established at the agency's initiative to provide it with technical assistance related to the development and evaluation of drugs, biologics, and medical devices, to lend credibility to its decisions and decision-making processes, and to provide a forum for public discussion of certain controversial issues.
The IOM committee believes that the primary role of FDA technical advisory committees is and should be to provide independent expert
scientific advice to the agency. It also believes that the existing FDA advisory committee system is fundamentally sound, has served the agency well, and does not need wholesale reorganization. It should be retained and strengthened. However, the IOM committee recommends a number of administrative and procedural changes that are designed to improve the performance and usefulness of the advisory committee system, to strengthen its management, and to increase its accountability.
In response to the agency's request, the report seeks to provide FDA with operational guidance on the use of its advisory committees. In doing so, it examines and makes recommendations on the recruitment and acquisition of committee membership, the agency's management of the financial conflict of interest and intellectual bias of committee members, and the operations and management of the advisory committee system.
The control of financial conflict of interest received more of the IOM committee's attention than any other topic. This priority, which was the foremost concern of the Commissioner, stemmed in large measure from the fact that the rapid change in the criteria and procedures by which conflict of interest controls were administered appeared to be impairing the FDA's ability to use advisory committees.
The issues of financial conflict of interest and of intellectual bias are great concern to the scientific community at the present time. They pervade many realms of science and medicine and have highly complex manifestations in specific institutional contexts. The IOM committee considered these issues, however, in relation to FDA's regulatory responsibilities for the evaluation of drugs, biologics, and medical devices. Consequently, this report gives great weight to the legal and administrative aspects of these matters, as these were the immediate source of FDA's problems. Although the report acknowledges the importance of broader concerns for conflict of interest and intellectual bias, it does not examine them at any length.
The IOM committee found great variation in the way advisory committees were used by the three centers responsible for drugs, biologics, and medical devices—the Centers for Drug Evaluation and Research, Biologic Evaluation and Research, and Devices and Radiological Health. One theme that runs throughout this report, therefore, calls for the development of uniform guidelines applicable to advisory committees across the three centers and for the elimination of unnecessary differences.
Another theme embedded in the IOM committee's recommendations is the need for FDA to ensure the independence of its advisory committees. In the highly-charged environment surrounding product evaluation by the FDA, charges that it seeks to influence the outcome of committee deliberations may or may not have merit but are often made by interested parties. As a result, ascertaining the validity of such charges can be very difficult.
appear to be, able to provide independent expert advice, and point to the uniform policies and procedures needed to ensure committee independence.
Finally, the committee focuses on a number of steps that the FDA should take to strengthen its management of the advisory committee system, from the Office of the Commissioner to the professionals who staff advisory committee operations. The IOM committees recommendations in this area strike a balance between those who urge a high degree of centralization of committee management in the Office of the Commissioner and those who argue that no change is warranted.
In sum, the IOM committee has attempted in this report to provide the agency with the guidance it sought in order to enhance the use of advisory committees in the evaluation of drugs, biologics, and medical devices, to improve the agency's management of the advisory committee system, and to increase the accountability of that system to the general public.
Notes
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Acknowledgments
This report results from the deliberations of the Institute of Medicine Committee to Study the Use of Advisory Committees by the Food and Drug Administration. The recommendations of the report reflect the judgments of the committee.
The actual preparation of the report under the direction of the committee has been accomplished by the collective efforts of committee members, project staff, and other contributors. The committee gratefully acknowledges these contributions.
The committee thanks the authors of the background papers that it commissioned, which provided valuable input to its deliberations. These authors include: Wendy E. Anderson, Scott Davidson, Laurie M.C. Faro, Gokuraju K. Raju, and Paul K. Stockman. Rebecca Wallace was a consultant to the project and prepared the analysis on which Appendix A was based.
The committee expresses its appreciation to the Industry Liaison Panel that it convened to advise it, especially to Marion J. Finkel, its chair. The other members were: N. Kirby Alton, Scott A. Hensley, Bruce Merchant, George Ohye, Martin Rose, Eve Ross, and R. William Soller.
Support for the study was provided by the Department of Health and Human Services, Food and Drug Administration (Contract No. 223-91-8050). Equally important to the successful conduct of the study was the cooperation of the Food and Drug Administration staff. The committee thanks David A. Kessler, Mary K. Pendergast, Carol R. Scheman, Jane E. Henney, Mary Jo Veverka, Amanda B. Pedersen, Patricia M. Kuntze, Dolores D. Willis, Carl C. Peck, D. Bruce Burlington, Gerald F. Meyer, Robert J. Temple, James M. Bilstad, Mary Doug Tyson, John Treacy, Issac Roubein, Kathryn C. Zoon, Gerald V. Quinnan, Jack Gertzog, James S. Benson, Halyna Breslawec, and Nancy Pluhowski. It also thanks the many division directors and executive secretaries who gave generously of their time in interviews by the project staff. Our special thanks go to James Weixel, project officer, and Stuart L. Nightingale, who oversaw the study.
in interviews by the project staff. Our special thanks go to James Weixel, project officer, and Stuart L. Nightingale, who oversaw the study.
In her capacity as Director of the Division of Health Sciences Policy, Ruth Ellen Bulger provided valuable guidance over the duration of the project. Stanley W. Ammons and Holly Dawkins provided able support as members of the project staff. Thelma Cox, project assistant, saw the study through from start to finish with unflappable grace.
List of Abbreviations
CBER
Center for Biologics Evaluation and Research
CDER
Center for Drug Evaluation and Research
CDRH
Center for Devices and Radiological Health
CFR
Code of Federal Regulations
CGMP
Current Good Manufacturing Practice(s)
DHHS
Department of Health and Human Services
FACA
Federal Advisory Committee Act FDA Food and Drug Administration
FFDCA
Federal Food, Drug, and Cosmetic Act
FR
Federal Register
FOIA
Freedom of Information Act
GAO
General Accounting Office
GSA
General Services Administration
IDE
Investigational Device Exemption
IND
Investigational New Drug
NDA
New Drug Application
NIH
National Institutes of Health
OGC
Office of the General Counsel
OGE
Office of Government Ethics
OSCE
Office of the Special Counsel for Ethics, DHHS
PHS
Public Health Service
PMA
Premarket Approval (application)
SGE
Special Government Employees
SMDA
Safe Medical Devices Act (of 1990)
USP
United States Pharmacopeia
