Book Review

Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies

N Engl J Med 1994; 331:1033-1034October 13, 1994

Article

Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies
Edited By Anne C. Mastroianni, Ruth Faden, and Daniel Federman. 518 pp., in two volumes. Washington, D.C., National Academy Press, 1994. Vol. 1, $34.95; ISBN: 0-309-04992-X Vol. 2, $29

Several recent reviews in professional journals have begun with the author's expressed hope that the book under review would merit a positive report, only to continue “But alas....” There is no “but alas” in my response to this two-volume series on ethical and legal issues related to the inclusion of women in clinical studies. It is an excellent work. My only “alas” is that it has taken so many years for such a substantive set of issues to be addressed in depth.

Women and Health Research is a report of the work of an Institute of Medicine committee, convened in 1992, on the ethical and legal issues relating to the inclusion of women in clinical studies. Volume 1, consisting of an executive summary, eight topical chapters, and several appendixes, is the committee report. Volume 2 consists of 21 papers the committee commissioned or used as background.

The committee's charge was to examine the ethical and legal aspects of the use of women (especially pregnant women and women of childbearing potential) as subjects in clinical research, to provide recommendations for institutions and persons involved in such research, and to describe the present legal liabilities and protections. In the background of the work was a movement away from protectionist policies (which tend to exclude women from clinical studies) to more recent access-oriented policies (which tend to emphasize, even require, the overinclusion of women). The 16 members of the committee, all of them notable contributors to their own fields, represented a wide range of disciplines, including bioethics, law, epidemiology and biostatistics, public health, medicine, and clinical research.

The preface to volume 1 and chapter 1 outline the major challenges the committee faced. Foremost was the lack of systematic information on the sexual composition of the populations in past and existing studies. As volume 1, chapter 2, aptly illustrates, there are data, but no comprehensive data. This is key, because a frequent argument for including women is based solely on their alleged underrepresentation in clinical studies and on the presumably negative results of such practices for them. The committee was sensitive to this, but wisely refrained from resting its entire study or its recommendations on such an assumption.

Instead, the committee members agreed that their 28 policy recommendations should rest on a broader concept of justice. (One of the 28 recommendations was that the broad-based concept be adopted.) Its components are distributive justice, which requires an equitable distribution of burdens and benefits between the sexes; social or compensatory justice, according to which those who “are currently oppressed in society should have a privileged place in studies... likely to be of specific benefit to them”; and procedural justice, which requires the groups affected by a research agenda to be included in the process of setting that agenda. The committee concludes that scientific institutions and investigators “must ensure that scientific advances... fairly benefit all people regardless of gender, race, ethnicity or age”; and that they need to establish policies of preferential treatment when the health interests of women, men, or other groups have not received a fair share of attention in research. In addition, subjects should be enrolled in clinical studies “in a manner that ensures that research yields scientifically generalizable results applicable to both genders.”

The remainder of volume 1 discusses the support for the committee's recommendations found in scientific understandings of sex; social and ethical considerations other than justice (such as scientific bias, views of the male as normative, constructions of race and ethnicity in Western societies, and participation by marginalized groups); and legal considerations. One chapter deals with the important matter of risks to the reproductive process and to offspring. The final chapter sets out a plan for implementation, addressing specific recommendations to investigators, institutional review boards, initial review groups, technical evaluation groups, scientific advisory councils, and the National Institutes of Health (NIH). Each site is given recommendations for “immediate action” and action “as soon as feasible.”

Each chapter concludes with a helpful recapitulation of the specific committee recommendations developed from the subject matter in that chapter. Also, each chapter includes references that offer readers the opportunity to examine further the perspective under discussion. The 50 pages of appendixes include reports of women's participation in clinical studies from 1977 through 1993, excerpts from the NIH Revitalization Act of 1993, a case study of diethylstilbestrol, and a list of compensation systems for research-related injuries. Several pages of biographical data on the committee members are also included.

The papers in volume 2 are presented without any reference to the report. I received and read this volume first. Not knowing what the first volume would hold, I found the basic themes hidden and often questioned the sequence in which the chapters were presented. For instance, the issue of why and whether women are underrepresented is addressed in at least five pieces, each from a slightly different angle. And although the brief introduction suggested that the book was organized around the idea of justice, this did not become apparent until I had read several chapters. For these reasons, I recommend volume 2 as an addition to volume 1 but less heartily as a stand-alone piece.

With that caveat, the reader can expect individual entries of high quality by a wide range of thinkers and doers. I found the discussions of ethical issues related to the inclusion of pregnant women and women of childbearing age in clinical trials especially engaging and instructive. For some readers, one of the surprises in the committee report will be the recommendation to include such women in clinical studies, with certain exclusions. Volume 2 lays the ethical, legal, and practical groundwork for that recommendation. At least five articles focus explicitly on the often-neglected issues of race and ethnic background.

These books are designed to be timely, and therefore some of the material will quickly become dated. For instance, the editors note that during the 1993 workshop, when the papers in volume 2 were presented, the Food and Drug Administration announced its intention to reverse its policy on excluding women from phase 1 and early phase 2 drug trials. This change in policy was implemented shortly thereafter and is not reflected in the book. Nor do these volumes reflect the passage of the NIH Revitalization Act, which brought sweeping changes in federal policies with regard to women's participation in clinical studies. Nevertheless, these books contain much that will stand firm against the rising tide of change in this evolving and critical area.

Ruth B. Purtilo, Ph.D.
Creighton University Center for Health Policy and Ethics, Omaha, NE 68178