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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 competences and with regard for 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 adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is the president of the Institute of Medicine.
This study was supported by project no. NO1-WH-3-2114 from the National Institutes of Health.
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COMMITTEE TO REVIEW THE NATIONAL INSTITUTES OF HEALTH WOMEN'S HEALTH INITIATIVE
MARION J. FINKEL (Chair),
Sandoz Pharmaceuticals Corporation, East Hanover, New Jersey
Howard University Cancer Center
ABDELMONEM A. AFIFI,
University of California, Los Angeles
KELLY D. BROWNELL,
GARY R. CUTTER,
Pythagoras, Inc., Birmingham, Alabama
JOHN W. FARQUHAR, *
Stanford University School of Medicine
M.R.C. GREENWOOD, *
University of California, Davis (Resigned July 7, 1993) Stanford University School of Medicine
PENNY M. KRIS-ETHERTON,
The Pennsylvania State University
Dartmouth Medical School
Slone Epidemiology Unit, Boston University School of Medicine
DIANE B. STOY,
The George Washington University Medical Center
SUSAN THAUL, Study Director
DANA HOTRA, Research Associate
FELICE LEPAR, Research Assistant
DONNA ALLEN, Project Assistant
Member, Institute of Medicine
FOOD AND NUTRITION BOARD
M.R.C. GREENWOOD * (Chair),
University of California, Davis
EDWIN L. BIERMAN * (Vice Chair),
University of Washington School of Medicine
PERRY L. ADKISSON, *
Department of Entomology, Texas A&M University
LINDSAY H. ALLEN,
Nutritional Sciences, University of Connecticut
DENNIS M. BIER,
Pediatric Endocrinology and Metabolism, Washington University School of Medicine
HECTOR F. DELUCA, †
Department of Biochemistry, University of Wisconsin, Madison
MICHAEL P. DOYLE,
Department of Food Science and Technology, University of Georgia
JOHANNA T. DWYER,
Frances Stern Nutrition Center, New England Medical Center Hospital, Boston
JOHN W. ERDMAN, JR.,
University of Illinois, Urbana
Division of Nutritional Sciences, Cornell University
Department of Pediatrics, University of Colorado Medical Center, Denver
JANET C. KING,
Department of Nutritional Sciences, University of California, Berkeley
LAURENCE N. KOLONEL,
Cancer Center of Hawaii, University of Hawaii, Honolulu
Graduate School of Biomedical Sciences, University of Texas, San Antonio
ALFRED SOMMER, *
School of Hygiene and Public Health, The Johns Hopkins University
VERNON R. YOUNG, *
Laboratory of Human Nutrition, Massachusetts Institute of Technology
STEVE L. TAYLOR (Ex Officio),
Department of Food Science and Technology, University of Nebraska
ARTHUR H. RUBENSTEIN * (IOM Council Liaison),
Department of Medicine, The University of Chicago
CATHERINE E. WOTEKI, Director
MARCIA LEWIS, Administrative Assistant
SUSAN WYATT, Financial Associate
Member, Institute of Medicine
Member, National Academy of Sciences
BOARD ON HEALTH SCIENCES POLICY
J. CLAUDE BENNETT * (Chair),
Department of Medicine, The University of Alabama School of Medicine, Birmingham
DAVID R. CHALLONER, *
University of Florida
RAMZI S. COTRAN, *
Harvard Medical School, Department of Pathology
DEBORAH COTTON, *
Health Policy & Management, Harvard School of Public Health
EMILIO DADDARIO, * Attorney,
WILLIAM N. HUBBARD, JR., * Retired President,
The Upjohn Company, Hickory Corners, Michigan
THOMAS INUI, *
Department of Ambulatory Care and Prevention, Harvard Medical School
RICHARD J. JOHNS, *
Department of Biomedical Engineering, The Johns Hopkins University School of Medicine
ERIC R. KANDEL, *
Center for Neurobiology & Behavior, Columbia College of Physicians and Surgeons
PATRICIA A. KING, *
Georgetown University Law Center
ELAINE L. LARSON,
School of Nursing, Georgetown University
JOSHUA LEDERBERG, *
The Rockefeller University
ROBERT I. LEVY, *
Wyeth-Ayerst Research, Philadelphia
MARY LAKE POLAN,
Department of Obstetrics and Gynecology, Stanford University
JOHN D. STOBO,
Department of Medicine and Physician-In-Chief, The Johns Hopkins Hospital
JOHN E. WENNBERG, *
The Center for the Evaluative Clinical Sciences, Dartmouth Medical School
JEAN DONALD WILSON,
Department of Internal Medicine, University of Texas, Southwestern Medical Center, Dallas
VALERIE P. SETLOW, Director
RUTH E. BULGER, Senior Program Officer
JOSEPH CASSELLS, Senior Program Officer
PHILOMINA MAMMEN, Administrative Assistant
Member, Institute of Medicine
For many years women have not been included in large prospective trials examining the benefits and risks of therapeutic interventions in diseases with significant morbidity and mortality that are common to both men and women. Such exclusion was not due to a lack of concern for the health of women, but rather an assumption that results obtained in men could be extrapolated to women. Other reasons for excluding women from clinical trials included concerns about the difficulty of recruiting and retaining women as compared with men and the need to increase sample size and costs. Implicit in the argument for larger sample sizes, ironically, is the need for a separate analysis by gender, which undercuts the assumption that the results can be extrapolated from males to females.
More recent research with drug therapy has shown important pharmacokinetic differences between males and females, as well as differences in risks and, in some cases, benefits. Thus, it is appropriate to conduct large scale studies in women who have or acquire diseases that are common to both sexes. In addition, women are at great risk for diseases like osteoporosis and breast cancer, for which additional prevention strategies are sorely needed.
The National Institutes of Health (NIH) has invested considerable resources in the past few years to rectify the inequities in research involving women and much useful information is expected to accrue from these efforts. The Women's Health Initiative (WHI) goes beyond NIH's earlier efforts—it is an attempt to not only gather data from over 100,000 women, but also to influence a change in lifestyles toward a healthier future.
The committee constituted by the Institute of Medicine (IOM) to review the WHI protocol faced a challenging task of reviewing a study that already had awarded large multi-year contracts and that was to begin participant recruitment during the IOM committee's review period.
There is a tension evident throughout this report. Had this committee been asked to design a plan for women's health research, it would not have designed this WHI. Although some committee members would have preferred that the WHI be cancelled, others were more willing to take the gamble. The committee focused on what aspects of the WHI
it did and did not consider scientifically justifiable and feasible. As will be seen, the committee recommended that the ongoing WHI could proceed but should be modified.
The committee wishes to express its appreciation to the many people who made important contributions to this report by providing source materials or special written reports, sharing their views during meetings, commenting on drafts, or otherwise serving as resource persons. In particular, the committee wishes to thank Dr. Louise Brinton, National Cancer Institute; Dr. M.R.C. Greenwood, University of California at Davis; Dr. J. Christopher Gallagher, Creighton University Medical Center; Dr. David Hunter, Harvard University; Dr. William Insull, Lipid Research Clinic, Houston, TX; Gayle Mowbray, The Johns Hopkins University; Paul Phelps, a free-lance editor and writer; Dr. John Potter, University of Minnesota; and Dr. Christopher Sempos, National Center for Health Statistics.
Many people at NIH shared generously of their time to supply the committee with the documents necessary to perform this review. Susan Clark, Project Officer; Dr. Caroline Clifford, Chief, Diet and Cancer Branch, National Cancer Institute; Laurence Freedman, Acting Chief, Biometry Branch, NCI; Linda Gardner, Contracts Specialist; Dr. William Harlan, Co-Director, WHI; Dr. Carrie Hunter, Special Assistant to the Director, Office of Research on Women's Health; and Dr. Jacques Rossouw, Project Officer, WHI Clinical Trial and Observational Study went to special efforts to assist IOM staff.
The committee would also like to thank Dr. Ross Prentice, Principal Investigator of the WHI Clinical Coordinating Center, and the representatives from the Vanguard Clinical Centers, who were able to join the committee on extremely short notice for its July 1993 meeting and provided valuable information about details of the WHI.
The necessity for rapid review required herculean efforts on the part of the IOM staff, particularly the Study Director, Dr. Susan Thaul, to prepare background material and to formulate the issues for review. The committee itself had only three meetings, at monthly intervals, to debate the issues and to prepare draft statements on several topics. At these meetings, and also behind the scenes, Dr. Thaul and Dr. Catherine E. Woteki, the Director of the IOM's Food and Nutrition Board, provided skillful guidance and input.
The study report itself was thoroughly prepared by Dr. Thaul and Dana Hotra, Research Associate. They not only had to synthesize the discussions that took place at the meetings but also to interpret a multiplicity of comments and recommendations into a report with which all members could agree. In addition, they made major contributions to the report using their own expertise. The committee could not have accomplished its goals in the brief period allotted to it without their dedicated efforts.
The committee also wishes to thank Dr. Ruth Bulger, the past Director of the IOM Health Sciences Policy Division, who was instrumental in developing this project for the IOM; Claudia Carl, Administrative Associate in the IOM Reports and Information Office; Robert Earl, Program Officer; Michael Edington, Managing Editor, Reports and Information
Office; Geraldine Kennedo, Project Assistant; Felice LePar, Research Assistant; Marcia Lewis, Administrative Assistant; Dr. Valerie P. Setlow, Director of the Health Sciences Policy Division of the IOM; Susan M. Wyatt, IOM Financial Associate; and the staff of the Food and Nutrition Board for their support.
Finally, much appreciation is also due to Donna Allen, Project Assistant, who smoothed the way for the committee members and the rest of the IOM staff.
Marion J. Finkel, M.D.