Pursuing Reform in Clinical Research: Lessons from Women's Experience

See Press Release from President Bill Clinton, “Remarks by the President in Apology for Study Done in Tuskegee” (May 16, 1997). For a comprehensive examination of the study, see Jones J.H. , Bad Blood (New York: Free Press, 1993).

See Epstein S. , “The Construction of Lay Expertise: AIDS Activism and the Forging of Credibility in the Reform of Clinical Trials,” Science, Technology, and Human Values, 20 (1995): 408–37; and Advisory Committee on Human Radiation Experiments, Final Report of the Advisory Committee on Human Radiation Experiments (New York: Oxford University Press, 1996).

The projects of the National Bioethics Advisory Commission include: Advising the National Science and Technology Council and other government entities concerning policies, guidelines, and regulations as they relate to human subjects research; and proposing guidelines for research on the cognitively impaired and on the use of human biological materials, as well as on research in international contexts. See “Protection of Human Research Subjects and Creation of National Bioethics Advisory Commission,” Exec. Order. No. 12975, 60 Fed. Reg. 52,063–65 (Oct. 5, 1995). Adding to recent research policy initiatives are rules for emergency research. See “Protection of Human Subjects; Informed Consent and Waiver of Informed Consent Requirements in Certain Emergency Research,” 61 Fed. Reg. 51,497–533 (Oct. 2, 1996).

See Lurie P. Wolfe S.M. , “Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries,” N. Engl. J. Med., 337 (1997): 853–56; Varmus H. Satcher D. , “Ethical Complexities of Conducting Research in Developing Countries,” N. Engl. J. Med., 337 (1997): 1003–05; and Office of the Inspector General, Department of Health and Human Services, Institutional Review Boards: A Time for Reform (Washington, D.C.: Office of the Inspector General, 1998).

These traditions provide the framework found in: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (Washington, D.C.: U.S. Government Printing Office, 1979); Jonas H. , “Philosophical Reflections on Experimenting with Human Subjects,” Daedalus: Journal of the American Academy of Arts and Sciences, Spring (1969): 219–47; and Hellman S. Hellman D.S. , “Of Mice but Not Men: Problems of the Randomized Clinical Trial,” N. Engl. J. Med., 324 (1991): 1585–89.

See also Sherwin S. , “Research,” in Sherwin S. , No Longer Patient: Feminist Ethics and Health Care (Philadelphia: Temple University Press, 1992): 158–75; and Mastroianni A.C. Faden R. Federman D. , eds., Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies (Washington, D.C.: National Academy Press, 1994).

See, for example, Gurwitz J.H. Col N.F. Avorn J. , “The Exclusion of the Elderly and Women from Clinical Trials in Acute Myocardial Infarction,” JAMA, 268 (1992): 1417–22; Faden R. Kass N. McGraw D. , “Women as Vessels and Vectors: Lessons from the HIV Epidemic,” in Wolf S.M. , ed., Feminism and Bioethics: Beyond Reproduction (New York: Oxford University Press, 1996): 252–81; Kinney E.L. , “Underrepresentation of Women in New Drug Trials: Ramifications and Remedies,” Annals of Internal Medicine, 95 (1981): 495–99.

See Wenger N.K. , “Exclusion of the Elderly and Women from Coronary Trials: Is Their Quality of Care Compromised?,” JAMA, 268 (1992): 1460–61; Hamilton J.A. Parry B. , “Sex-Related Difference in Clinical Drug Response: Implications for Women's Health,” Journal of the American Medical Women's Association, 38 (1983): 126–32; and Bell N.K. , “Women and AIDS: Too Little, Too Late?,” in Holmes H.B. Purdy L.M. , eds., Feminist Perspectives in Medical Ethics (Bloomington: Indiana University Press, 1992): 46–62.

See Kass N.E. Taylor H.A. King P.A. , “Harms of Excluding Pregnant Women from Clinical Research: The Case of HIV-Infected Pregnant Women,” Journal of Law, Medicine & Ethics, 24 (1996): 36–46. As of this writing, proposed changes to Subpart B, § 45 C.F.R. 46, embrace a strengthened role for the consent process in research with pregnant women. Save for one notable suggested revision—that the consent of the woman alone is adequate—the proposed regulations are no less restrictive with respect to their inclusion than those already in place. See “Protection of Human Research Subjects: Proposed Rule,” 63 Fed. Reg. 27,793–804 (May 20, 1998).

It bears mention here that the transition from protectionism, where research burdens are emphasized, to the claim that the opportunity to participate is a matter of justice, where the focus is on potential benefits, came about chiefly through the efforts of activists seeking access to experimental drugs for people with acquired immune deficiency syndrome. See Epstein , supra note 2; Bayer R. , “Beyond the Burdens of Protection: AIDS and the Ethics of Research,” Evaluation Review, 14 (1990): 443–46; and Levine R.J. , “The Impact of HIV Infection on Society's Perception of Clinical Trials,” Kennedy Institute of Ethics Journal, 4 (1994): 93–98.

For a brief history of the use and impact of thalidomide and diethylstilbestrol, see Levine C. , “Women and HIV/AIDS Research: The Barriers to Equity,” Evaluation Review, 14 (1990): 452–54. Another source includes Apfel R.J. Fisher S.M. , To Do No Harm: DES and the Dilemmas of Modern Medicine (New Haven: Yale University Press, 1984). For discussion of the harms associated with intrauterine devices, see Ruzek S.B. , The Women's Health Movement: Feminist Alternatives to Medical Control (New York: Praeger, 1978): At 43–44.

See Food and Drug Administration, General Considerations for the Clinical Evaluation of Drugs (Washington, D.C.: U.S. Government Printing Office, 1977): At 10; and National Institutes of Health, Code of Federal Regulations Title 45 Part 46 (Washington, D.C.: U.S. Government Printing Office, 1991): At subpart B (“Additional Protections Pertaining to Research, Development, and Related Activities Involving Fetuses, Pregnant Women, and Human In Vitro Fertilization”).

See, for example, Oberman M. , “Real and Perceived Legal Barriers to the Inclusion of Women in Clinical Trials,” in Dan A.J. , ed., Reframing Women's Health: Multidisciplinary Research and Practice (Thousand Oaks: Sage, 1994): 266–76; and Merton V. , “The Exclusion of Pregnant, Pregnable, and Once Pregnable People (A.K.A. Women) from Biomedical Research,” American Journal of Law & Medicine, XIX (1993): 369–451.

See, for example, Warren N. , “Out of the Question: Obstacles to Research on HIV and Women Who Engage in Sexual Behaviors with Women,” SIECUS Report, 22, no. 1 (1993): 13–16; White E.C. , ed., The Black Women's Health Book: Speaking for Ourselves (Seattle: Seal Press, 1990); and El-Sadir W. Capps L. , “The Challenge of Minority Recruitment in Clinical Trials for AIDS,” JAMA, 267 (1992): 954–57.

See Luzuriaga K. Sullivan J.L. , “Pathogenesis of Vertical HIV-1 Infection: Implications for Intervention and Management,” Pediatric Annals, 23 (1994): 159–66; and Ammann A.J. , “Human Immunodeficiency Virus Infection/AIDS in Children: The Next Decade,” Pediatrics, 93 (1994): 930–35.

See Coleman B.C. , “AMA Backs Mandatory HIV Tests for All Pregnant Women: Critics Fear Some Will Avoid Prenatal Care,” Washington Post, June 28, 1996, at A02.

See id.; and Rothenberg K.H. Paskey S.J. , “The Risk of Domestic Violence and Women with HIV Infection: Implications for Partner Notification, Public Policy and Law,” American Journal of Public Health, 85 (1995): 1569–76.

Seaman B. , Free and Female (New York: Fawcett, 1972): At 180–81.

See, for example, Mouton C.P. , “Barriers to Black Women's Participation in Cancer Clinical Trials,” Journal of the National Medical Association, 89 (1997): 721–27.

Young I.M. , Justice and the Politics of Difference (Princeton: Princeton University Press, 1990): At 59.

Consider, for example, the use of slave women as research subjects in the Antebellum South. See Sims J.M. , The Story of My Life (New York: Appleton, 1889). In more recent memory, of course, is the Tuskegee Syphilis Study. See Gamble V.N. , “Under the Shadow of Tuskegee: African-Americans and Health Care,” American Journal of Public Health, 87 (1997): 1773–78; and Allen M. , “The Dilemma for Women of Color in Clinical Trials,” Journal of the American Medical Women's Association, 49 (1994): 105–09.

See Dresser R. , “Wanted: Single, White Male for Medical Research,” Hastings Center Report, 22, no. 1 (1992): 24–29, at 28. On bias in definitions of what constitutes economic activity, or what is considered “productive,” see Pujol M. , “Into the Margin!,” in Kuiper E. Sap J. , eds., Out of the Margin: Feminist Perspectives on Economics (New York: Routledge, 1995): 17–34.

Paul Starr notes that, since World War II, science, including medical research, has come to be regarded as a national asset. Investment in medical research has been seen as an especially appealing avenue for expansion because it promises improvements in the quality of life without the major social reorganization required, for example, by the implementation of national health insurance. Concerns about disturbing the medical profession loomed large in this assessment. During this period, funding of research has shifted from being a largely private, voluntary effort to a federal one, based substantially on public investment. See Starr P. , The Social Transformation of American Medicine (New York: Basic Books, 1982): At 338–47.

See Kasper A.S. , “An Economic Policy Primer for Women's Health,” Paper Presented at Meeting “Urban Women's Health: Models for the Future, Health and Medicine Policy Research Group,” Chicago (Nov. 1996) (on file with author). See also Zuckerman D. Yoon Y.H. Hartmann H. , “Part Time Opportunities for Professionals and Managers: Who Are They, Who Uses Them, and Why?” (Washington, D.C.: Institute for Women's Policy Research, 1998); Shaw L.B. , “The Impact of the Glass Ceiling and Structural Change on Women and Minorities” (Washington, D.C.: Institute for Women's Policy Research, 1995); and Spalter-Roth R.M. Hartmann H.I. , “Contingent Work: From Entitlement to Privilege” (Washington, D.C.: Institute for Women's Policy Research, 1995).

See Shaw , supra note 24.

See id.

See Falik M.M. Collins K.S. , eds., The Commonwealth Fund Survey on Women's Health (Baltimore: Johns Hopkins University Press, 1996); Institute for Women's Policy Research, The Status of Women in the States, 1998–1999 (Washington, D.C.: Institute for Women's Policy Research, 1999). See also Mahowald M.B. , “The Feminization of Poverty: Its Impact on Women's and Children's Health,” in Mahowald M.B. , Women and Children in Health Care: An Unequal Majority (New York: Oxford University Press, 1993): 217–35.

See Cotton D.J. , “Determinants of Accrual of Women to a Large, Multicenter Clinical Trials Program of Human Immunodeficiency Virus Infection,” Journal of Acquired Immune Deficiency Syndromes, 6 (1993): 1322–28.

See Goldberg C. , “Cutting a Lifeline to AIDS Study,” New York Times, Jan. 30, 1996 at B1, B5. The Inspector General's report on institutional review boards also highlights this concern.

The implicit assumption here is that women researchers would be more likely to investigate conditions and questions of importance to women and/or to utilize women subjects. See Harding S. , “Women's Standpoints on Nature: What Makes Them Possible?,” Osiris, 12 (1997): 186–200. In the realm of popular commentary, consider former U.S. Representative Patricia Schroeder's now famous quote: “[Y]ou fund what you fear. When you have a male dominated group of researchers, they are more worried about prostate cancer than breast cancer.” Goodman E. , Editorial, “A Health Research Bias,” Boston Globe, June 21, 1990, at 15. Cotton Deborah demonstrated the significance of women serving as researchers in finding that AIDS Clinical Trials Group units with female principal investigators of co-principal investigators had more than twice the percentage of females enrolled as units headed by men. See Cotton , supra note 28.

These points are discussed by Office of Research on Women's Health, National Institutes of Health, Women in Biomedical Careers: Dynamics of Change, Strategies for the 21st Century (Bethesda: National Institutes of Health, 1992); and Bowles L.E. , “The Disenfranchisement of Women in Clinical Trials: The Legal Ramifications of and Solutions for Rectifying the Knowledge Gap,” Vanderbilt Law Review, 45 (1992): 877–920, at 882–83.

See Campbell P.W. , “NIH Finds That Congressional Largesse Is Followed By Congressional Scrutiny,” Chronicle of Higher Education, Jan. 22, 1999, at A24.

See Blumenthal D. Meyer G.S. , “Academic Health Centers in a Changing Environment,” Health Affairs, 15, no. 2 (1996): 200–15.

See Society for the Advancement of Women's Health Research, Women's Health in a Changing Economic Environment: The Impact of Managed Care on Women's Health Research (Washington, D.C.: Society for the Advancement of Women's Health Research, 1996).

See, for example, Task Force on Women's Health Issues, National Institutes of Health, Report of the Public Health Service Task Force on Women's Health Issues (Washington, D.C.: U.S. Government Printing Office, Vols. 1 & 2, 1987); and Subcommittee on Housing and Consumer Interests of the House Committee on Aging, U.S. Congress, Women Health Care Consumers: Short Changed on Medical Research and Treatment (Washington, D.C.: U.S. Government Printing Office, 1991).

See Connor E.M. , “Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment,” N. Engl. J. Med., 331 (1994): 1173–80.

See Faden Kass McGraw , supra note 7.

See Dickerson K. , “Reinventing Health Outcomes Research Related to Breast Cancer,” Paper Presented at Meeting “Health Outcomes Research,” Chicago (Mar. 1996) (on file with author).

See Secker B. , “Destroying the Right/Power to Decide: The Gender Politics of Incompetence Labeling,” Journal of Social Philosophy, (1999) (forthcoming); Council on Ethical and Judicial Affairs, American Medical Association, “Gender Disparities in Clinical Decision Making,” JAMA, 266 (1991): 559–62; and Fisher S.M. , In the Patient's Best Interest: Women and the Politics of Medical Decisions (New Brunswick: Rutgers University Press, 1988).

See Lloyd G. , The Man of Reason: ‘Male’ and ‘Female’ in Western Philosophy (Minneapolis: University of Minnesota Press, 1984); and Harding S. , “Rethinking Standpoint Epistemology: What Is ‘Strong Objectivity’?,” in Alcoff L. Potter E. , eds., Feminist Epistemologies (New York: Routledge, 1993): 49–82.

See “NIH Guidelines Concerning the Inclusion of Women and Minorities as Subjects in Clinical Research,” 59 Fed. Reg. 14,507–13 (Mar. 28, 1994); “Guidelines for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs,” 58 Fed. Reg. 39,405–16 (July 22, 1993); and “Investigational New Drug Applications; Proposed Amendment to Clinical Hold Regulations for Products Intended for Life-Threatening Diseases,” 62 Fed. Reg. 49,946–54 (Sept. 24, 1997).

See Young , supra note 20, at 173.

Id. at 171–72.

59 Fed Reg. at 14,509.

The Food and Drug Administration's 1977 General Considerations for the Clinical Evaluation of Drugs officially placed restrictions on the inclusion of premenopausal women capable of becoming pregnant, of women using oral, injectable, and mechanical contraception, as well as of married women whose partners had undergone vasectomies or who were using contraceptives. In practice, the policy was extended even further to deny participation to lesbians not seeking pregnancy, sexually inactive women, those who had undergone hysterectomies, or were otherwise infertile, and postmenopausal women. See Hamilton J.A. , “Women and Health Policy: On the Inclusion of Females in Clinical Trials,” in Sargent C.F. Bretell C.B. , eds., Gender and Health: An International Perspective (Englewood Cliffs: Prentice Hall, 1996): At 294–95.

The Institute of Medicine's Committee on the Ethical and Legal Issues of Including Women in Clinical Studies reached similar conclusions. See Mastroianni Faden Federman , supra note 6.

See Frederiksen M.C. , “Clinical Trials in Pregnancy,” Food and Drug Law Journal, 48 (1993): 195–96; and Charo A. , “Protecting Us to Death: Women, Pregnancy, and Clinical Research Trials,” Saint Louis Law Journal, 38 (1993): 135–88.

The following Supreme Court cases support this view: Cruzan v. Director, Missouri Department of Health, 497 U.S. 261 (1990); Griswold v. Connecticut, 381 U.S. 479 (1965); Roe v. Wade, 410 U.S. 113 (1973); and International Union v. Johnson Controls Inc., 499 U.S. 187 (1991). For detailed discussions of the relevance of the Fourteenth Amendment to the inclusion of women in clinical research, see Gorenberg H. White A. , “Off the Pedestal and Into the Arena: Toward Including Women in Experimental Protocols,” N.Y.U. Review of Law and Social Change, 19 (1991–1992): 233–35; and Rothenberg K.H. , “Gender Matters: Implications for Clinical Research and Women's Health Care,” Houston Law Review, 32 (1996): 1201–72, at 1246–48.

For additional discussion, see Baylis F. , “Women and Health Research: Working for Change,” Journal of Clinical Ethics, 7 (1996): 229–42; Kass Taylor King , supra note 9; and Mastroianni Faden Federman , supra note 6.

See Merton , supra note 13.

See Eckenwiler L.A. , “Attention to Difference and Women's Consent to Research,” IRB: A Review of Human Subjects Research, 20, no. 6 (1998): 6–11.

Yu E.S.H. , “Ethical and Legal Issues Relating to the Inclusion of Asian/Pacific Islanders in Clinical Studies,” in Mastroianni Faden Federman , supra note 6, at 216–31.

For more on the theoretical point, see Young , supra note 20, at 72–73.

Starr notes that the triumphs of American scientists over the Nazis, who had centralized control over research, were taken as a testament to the independence of science from politics, for making a structural choice in favor of scientific autonomy so that “free” inquiry might flourish. See Starr , supra note 23, at 341–44. See also Shils E.A. , “The Autonomy of Science,” in Barber B. Hirsch W , eds., The Sociology of Science (New York: Free Press, 1962): 610–14.

See Harding , supra note 40, at 58.

See id. at 50–51.

Gaylin W. , “Scientific Research and Public Regulation,” Hastings Center Report, 5, no. 3 (1975): 5–7, at 6.

See Friedman M. , “The Impracticality of Impartiality,” Journal of Philosophy, 86 (1989): 645–56; and Benhabib S. , Situating the Self: Gender, Community, and Postmodernism in Contemporary Ethics (New York: Routledge, 1992): At 166–67.

Young , supra note 20, at 10.

Far from blaming them for this myopia, these theorists consider it an artifact of scientific education. See Harding S. , “Introduction: Eurocentric Scientific Illiteracy—A Challenge for the World Community,” in Harding S. , ed., The “Racial” Economy of Science: Toward a Democratic Future (Bloomington: Indiana University Press, 1993): At 1.

See Fraser N. , “Women, Welfare, and the Politics of Need Interpretation,” in Unruly Practices: Power, Discourse and Gender in Contemporary Social Theory (Minneapolis: University of Minnesota Press, 1989): 144–87; and Fraser N. , “Women, Welfare, and the Politics of Need Interpretation,” Hypatia: A Journal of Feminist Philosophy, 2 (1987): 103–21.

Young I.M. , “Communication and the Other: Beyond Deliberative Democracy,” in Benhabib S. , ed., Democracy and Difference: Contesting the Boundaries of the Political (Princeton: Princeton University Press, 1996): 121–35.

Id. at 122. See also White L.E. , “Subordination, Rhetorical Survival Skills, and Sunday Shoes: Notes on the Hearing of Mrs. G,” in Bartlett K.T. Kennedy R. , eds., Feminist Legal Theory: Readings in Law and Gender (Boulder: Westview Press, 1991): 404–28.

For ideas on how to do this, see Young , supra note 62.

See Levine C. Dubler N.N. Levine R.J. , “Building a New Consensus: Ethical Principles and Policies for Clinical Research on HIV/AIDS,” IRB: A Review of Human Subjects Research, 13, nos. 1–2 (1991): 1–17; and Merton V , “Community-Based AIDS Research,” Evaluation Review, 14 (1990): 502–37.

See Epstein , supra note 2.

See 45 C.F.R. § 46.107 for specifics on the guidelines.

Fraser N. , Justice Interruptus: Critical Reflections on the “Postsocialist Condition” (New York: Routledge, 1997): At 15.

See id. at 25.

See Merton , supra note 65, at 516–17.