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Food and Drug Administration Advisory Committees Food and Drug Administration Advisory Committees Committee To Study the Use of Advisory Committees by the Food and Drug Administration Richard A. Rettig, Laurence E. Earley, and Richard A. Merrill, Editors Division of Health Care Policy Institute of Medicine NATIONAL ACADEMY PRESS Washington, D.C. 1992
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Food and Drug Administration Advisory Committees NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W., Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the governing board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competencies and with regard to appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a report review committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this the Institute acts under both the Academy's 1863 congressional charter responsibility to be an advisor to the federal government and its own initiative in identifying issues of medical care, research, and education. Support for this project was provided by the Food and Drug Administration pursuant to Contract No. 223-91-8050. Library of Congress Catalog Card No. 92-62633 ISBN 0-309-04837-0 Copyright 1992 by the National Academy of Sciences. All rights reserved. Printed in the United States of America No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purpose of official use by the United States government. Additional copies of the report are available from: National Academy Press 2101 Constitution Avenue, N.W. Washington, DC 20418 B058 The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held at the Staatlichemuseen in Berlin. First Printing, October 1992 Second Printing, March 1993
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Food and Drug Administration Advisory Committees 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
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Food and Drug Administration Advisory Committees 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 * Member, Institute of Medicine
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Food and Drug Administration Advisory Committees 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
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Food and Drug Administration Advisory Committees 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.
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Food and Drug Administration Advisory Committees 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 1. Sheila Jasanoff, The Fifth Branch. Science Advisers as Policymakers (Cambridge, Mass., Harvard University Press, 1990). 2. Bruce L. R. Smith, The Advisers: Scientist in the Policy Process (Washington, D.C., The Brookings Institution, 1992).
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Food and Drug Administration Advisory Committees 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.
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Food and Drug Administration Advisory Committees 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.
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Food and Drug Administration Advisory Committees Contents Preface v Acknowledgments ix List of Abbreviations xii Summary 1 1 Introduction 33 2 Historical Evolution of FDA Advisory Committees 46 3 The FDA Advisory Committee System 70 4 Recurring Issues 100 5 Committee Membership 116 6 Ensuring Committee Integrity 127 7 Committee Operations 173 8 Organization and Management 196 Appendixes A Resource Implications 215 B Glossary 222
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Food and Drug Administration Advisory Committees 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