In the fall of 1992, at the request of the National Institutes of Health's (NIH) Office of Research on Women's Health, the Institute of Medicine formed a committee to study the ethical and legal issues relating to the inclusion of women in clinical studies. The NIH's request was coincident with a growing perception that biomedical research had focused more on the health problems of men relative to those of women, and that women have been denied access to advances in medical diagnosis and therapy as a result of being excluded from clinical studies. With pressure from women's health advocates mounting and legislative change on the horizon, NIH requested that the committee (1) consider the ethical and legal implications of including pregnant women and women of childbearing potential in clinical studies; (2) provide practical advice for consideration by NIH, institutional review boards, and clinical investigators; and (3) examine known instances of litigation regarding injuries to research subjects and describe issues of legal liability and possible protections. Comprised of sixteen members with expertise in bioethics, law, epidemiology and biostatistics, public health policy, obstetrics and gynecology, clinical research, pharmaceutical development, social and behavioral sciences, and clinical evaluative sciences, the committee held five meetings during the one-year study. Volume 1, Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, contains the committee's final report.

The committee's report begins with an assessment of the claims regarding women's participation in clinical trials; this introduction is followed by a summary of the history of women's participation in clinical research so that readers may gain an understanding of the origins of controversy and concern

surrounding this issue. An analysis of the principles of justice makes up the central chapter of the report. The committee chose to shape its report around considerations of justice in light of its understanding that calls to rectify women's alleged "underrepresentation" in clinical studies are based on concerns about the unequal distribution of the benefits of biomedical research. Subsequent chapters address the various challenges—scientific, social, ethical, and legal—to achieving justice in clinical studies. Each of the recommendations developed in these chapters flows from the central presumption embraced by the committee: that women and men should have the opportunity to participate equally in the benefits and burdens of research.

In an effort to solicit outside expertise on specific issues as well as gather input from interested individuals, the committee held an invitational workshop at the Georgetown University Conference Center on March 24–25, 1993. Speakers were invited by the committee to address such issues as recruitment and retention, liability, compensation, federal regulations, health consequences, and justice as they pertain to women's participation in clinical studies. Each speaker answered questions from the audience—a group of more than forty people from academia, industry, federal health agencies, and Congress.

This volume contains the text of the presentations given at the workshop. The presentation, Justice and the Inclusion of Women in Clinical Studies: A Conceptual Framework, by Professor Debra DeBruin, was expanded at the request of the committee, as this issue took on considerable importance in the committee's deliberations and final report. It is noteworthy that on the second day of the workshop, the Food and Drug Administration (FDA) announced its intention to reverse its 1977 guideline recommended the exclusion of women from early phases (Phase I and early Phase II) of drug development. Given the date of this announcement and of the formal issuance of new guidelines (July 22, 1993), the changes in FDA policy are not reflected in the presentations. Nor do the presentations take into account the June 10, 1993, passage of the NIH Revitalization Act, which also effected changes in federal policies regarding the inclusion of women in clinical studies.

Also included in this volume are additional papers commissioned by the committee. These papers address issues that were introduced at the workshop, but about which the committee felt the need for more in-depth analysis. Four of these papers focus on the research participation of women from specific racial and ethnic groups—American Indians, Alaskan Natives, Asian/Pacific Islanders, Blacks, and Latinos. In the fifth paper, the author attempts to answer the question, "Have women been 'underrepresented' in biomedical research?" through a systematic survey of clinical studies reported in the Journal of the American Medical Association.

The committee is indebted to the writers of this volume for their thought-provoking insights and scholarly presentation of opinions and ideas. Their work

stimulated thoughtful discussion, heated debate, and sometimes even consensus. It is the committee's hope that this volume, on its own and in conjunction with Volume 1, proves to be a valuable resource to policymakers, clinical investigators, and subjects alike.