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The Participation of Underrepresented Minorities in Clinical Research

Published online by Cambridge University Press:  06 January 2021

Barbara A. Noah
Barbara A. Noah*
Affiliation:
Health Law & Policy, Center for Governmental Responsibility, University of Florida College of Law; University of Florida College of Medicine and Member, University of Florida Institutional Review Board, Harvard Law School
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Extract

The past decade witnessed unprecedented growth in medical research involving human subjects, promising the development of new treatments that extend and improve the quality of life, as well as prevent disease. Recent biomedical breakthroughs such as the mapping of the human genome, improved understanding of pharmacokinetics and molecular biology, and novel theories about the mechanisms of diseases such as cancer have led to a proliferation of clinical trials. Such research provides the necessary bridge from scientific theory to practical medical application, and it is essential that these efforts benefit all persons who suffer from the studied diseases.

In addition to the potential long-term pay-offs, clinical trials may offer immediate dividends to enrolled subjects. The opportunity to participate in medical research carries with it a variety of potential risks and benefits. Because clinical trial participation potentially results in significant individual benefits, including access to state-of-the-art care and improved disease monitoring, fairness demands equal opportunity for inclusion whenever scientifically appropriate.

Type
Research Article
Information
American Journal of Law & Medicine , Volume 29 , Issue 2-3 , June 2003 , pp. 221 - 245
Copyright
Copyright © American Society of Law, Medicine and Ethics and Boston University 2003

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Footnotes

†

An earlier version of this paper was presented to the faculty at Florida State University College of Law, and I would like to thank those in attendance for their helpful suggestions.

References

1 See Editorial, Fifty Years of Randomized Controlled Trials, 317 BRIT. MED. J. 1165 (1998); Mariner, Wendy K., Human Subjects, NAT’L L.J., May 13, 2002Google Scholar, at A25; Okie, Susan, U.S. Oversight Urged for Human Research, WASH. POST, May 16, 2001Google Scholar, at A10 (noting the “explosive growth” of biomedical research, including an increase in federal spending for health research from $6.9 billion to $13.4 billion between 1986 and 1995, and an increase in industry research spending from $6.2 billion to $18.6 billion during the same time period). Estimates suggest that between 45,000 and 50,000 researchers currently conduct clinical trials in the United States. Id.; see also Eve E. Slater, IRB Reform, 346 NEW ENG. J. MED. 1402 (2002) (noting that federal funding for clinical research has more than doubled since 1995).

2 See Noah, Lars, Medicine's Epistemology: Mapping the Haphazard Diffusion of Knowledge in the Biomedical Community, 44 ARIZ. L. REV. 373, 382-95 (2002)Google Scholar.

3 Still, commentators have properly cautioned against confusing access to research involving experimental therapies (or standard therapies in an active control arm of a trial) with expanded access to healthcare. See REBECCA DRESSER, WHEN SCIENCE OFFERS SALVATION 64 (2001).

4 Commentators have recognized that subjects enrolled in clinical trials, regardless of whether they receive the experimental treatment or a placebo control, apparently achieve better outcomes than patients with the same condition who receive treatment from physicians. See Lantos, John D., The “Inclusion Benefit” in Clinical Trials, 134 J. PEDIATRICS 130, 130 (1999)Google Scholar (“A number of explanations have been offered for the apparent benefit of RCT participation, including selection bias, placebo effects, and adherence to well-defined protocols” for other aspects of disease management.); Vedantam, Shankar, Against Depression, Sugar Pill Is Hard to Beat, WASH. POST, May 7, 2002Google Scholar, at A1. Ironically, in at least one historical example of systematic research abuse, those initially excluded perceived participation as a benefit. See, e.g., ALLEN M. HORNBLUM, ACRES OF SKIN: HUMAN EXPERIMENTS AT HOLMESBURG PRISON 16 (1998). In a series of skin testing experiments of various chemical compounds and vaccines at the Holmesburg Prison, prisoner participants were paid $5.00 per test and initial participation was limited to white prisoners. Id. When African-American prisoners protested over the unfairness of this missed opportunity to earn extra prison benefits, they were later permitted to serve as test subjects, though they were frequently selected for the riskier experiments. Id. This sort of inclusion “benefit” clearly is not the type imagined by those who argue for racial justice in medical research.

5 In one survey of potential research participants, fifty-three percent of those questioned indicated that they would be willing to participate in research in order to secure better medical care. See Shavers, Vickie L. et al., Factors That Influence African-Americans’ Willingness to Participate in Medical Research Studies, 91 CANCER 233, 235 (2001)Google Scholar; see also Kolata, Gina & Eichenwald, Kurt, For the Uninsured, Drug Trials Are Health Care, N.Y. TIMES, June 22, 1999Google Scholar, at A1 (explaining that for the uninsured, clinical trials have become the primary source of medical care).

6 See, e.g., Merton, Vanessa, The Exclusion of Pregnant, Pregnable, and Once-Pregnable People (a.k.a. Women) from Biomedical Research, 19 AM. J.L. & MED. 369 (1993)Google Scholar; Scott, Joan W., How Did the Male Become the Normative Standard for Clinical Drug Trials?, 48 FOOD & DRUG L.J. 187, 187-88 (1993)Google Scholar (describing two contradictory assumptions—that women are identical to men so that female participation in drug trials is unnecessary, and that women are so unlike men that female participation in drug trials would destroy the purity of the experiment—that have contributed to this phenomenon); Elizabeth Bowles, L., Note, The Disenfranchisement of Fertile Women in Clinical Trials: The Legal Ramifications of and Solutions for Rectifying the Knowledge Gap, 45 VAND. L. REV. 877 (1992)Google Scholar.

7 Although this Article will refer primarily to African-Americans and their health needs, many of the arguments developed herein apply with equal force to other racial and ethnic minorities.

8 See Morehouse Sch. of Med., Med. Treatment & Effectiveness Ctr., A Synthesis of the Literature: Racial and Ethnic Differences in Access to Medical Care (1999), available at http://www.kff.org/content/1999/1526 (summarizing health literature from 1985-1999, including 180 studies, both with and without controls for explanatory variables, that provide evidence of racial disparities in health services).

9 See Council on Ethical & Judicial Affairs of the AMA, Black-White Disparities in Health Care, 263 JAMA 2344, 2344-45 (1990) (providing statistics on comparative mortality rates between races).

10 See Kaiser Family Found., Comm’n on Medicaid & the Uninsured, Racial and Ethnic Disparities in Access to Insurance and Health Care (July 31, 2000), at http://www.kff.org (describing this and other significant health disparities, and noting that access to treatment is difficult because almost one quarter of African-Americans have neither private health insurance nor Medicaid coverage, compared with only fifteen percent of whites who lack such coverage).

11 See Nat’l Cancer Inst., Cancer Health Disparities (Apr. 21, 2002), available at http://newscenter.cancer.gov/pressreleases/healthdisparities.html.

12 See Donnelly, John, HIV Toll Heavier on U.S. Blacks: New Cases on Rise in Disadvantatged, BOSTON GLOBE, July 8, 2002Google Scholar, at A1 (cautioning that the statistics were based on data compiled from twenty-five states and that the overall national picture may be different).

13 See DAVID BARTON SMITH, HEALTH CARE DIVIDED: RACE AND HEALING A NATION 191- 235 (1999) (describing a broad range of health disparities and the “persistence of a divided health system”); Epstein, Arnold M. & Ayanian, John Z., Racial Disparities in Medical Care, 344 NEW ENG. J. MED. 1471, 1471-72 (2001)Google Scholar. Epstein and Ayanian explain that “both white and black physicians may have subtle biases that are based on … social factors and that influence their judgments about patients’ suitability for procedures.” Id. at 1472. These types of differential utilization patterns persist even when investigators control for confounding variables such as income, level of education, insurance coverage, co-morbid factors and stage of disease. See Noah, Barbara A., Racial Disparities in the Delivery of Health Care, 35 SAN DIEGO L. REV. 135 (1998)Google Scholar (describing the body of research on health disparities and examining some of the underlying assumptions about the role of race in medicine).

14 See, e.g., Allison, John J. et al., Racial Differences in the Medical Treatment of Elderly Medicare Patients with Acute Myocardial Infarction, 11 J. GEN. INTERNAL MED. 736 (1996)Google Scholar; Canto, John G. et al., Relation of Race and Sex to the Use of Reperfusion Therapy in Medicare Beneficiaries with Acute Myocardial Infarction, 342 NEW ENG. J. MED. 1094, 1096-97 (2000)Google Scholar (concluding that African-Americans were less likely than whites to receive “potentially lifesaving” reperfusion therapy); Taylor, Herman A. et al., Management and Outcomes for Black Patients with Acute Myocardial Infarction in the Reperfusion Era, 82 AM. J. CARDIOLOGY 1019, 1020-21 (1998)Google Scholar (concluding that African-Americans are less likely than whites to receive intravenous thrombolytic therapy, coronary arteriography and other elective catheter-based procedures).

15 See, e.g., Ayanian, John Z. et al., The Effect of Patients’ Preferences on Racial Differences in Access to Renal Transplantation, 341 NEW ENG. J. MED. 1661 (1999)Google Scholar; Epstein, Arnold M. et al., Racial Disparities in Access to Renal Transplantation: Clinically Appropriate or Due to Underuse or Overuse?, 343 NEW ENG. J. MED. 1537 (2000)Google Scholar.

16 See, e.g., Bonham, Vence L., Race, Ethnicity, and Pain Treatment: Striving to Understand the Causes and Solutions to the Disparities in Pain Treatment, 29 J.L. MED. & ETHICS 52 (2001)Google Scholar; Sean Morrison, R. et al., “We Don't Carry That”–Failure of Pharmacies in Predominantly Nonwhite Neighborhoods to Stock Opioid Analgesics, 342 NEW ENG. J. MED. 1023 (2000)Google Scholar; Todd, Knox H. et al., Ethnicity and Analgesic Practice, 35 ANNALS EMERGENCY MED. 11, 13 (2000)Google Scholar (finding that, in the studied group of patients presenting in an emergency department with long-bone fractures, only fiftyseven percent of African-Americans received analgesics compared with seventy-four percent of white patients); Todd, Knox H. et al., Ethnicity as a Risk Factor for Inadequate Emergency Department Analgesia, 269 JAMA 1537 (1993)Google Scholar.

17 See, e.g., Fiscella, Kevin et al., Inequality in Quality: Addressing Socioeconomic, Racial, and Ethnic Disparities in Health Care, 283 JAMA 2579, 2581 (2000)Google Scholar (describing recent recommendations that the managed care industry collect socioeconomic and racial/ethnic data in its outcomes studies and noting that the U.S. Department of Health and Human Services (HHS) now requires sponsored data collection to include racial/ethnic categories); Hannan, Edward L., The Continuing Quest for Measuring and Improving Access to Necessary Care, 284 JAMA 2374, 2375 (2000)Google Scholar (“[T]he reasons minorities and the poor have accentuated access problems must be investigated … . There is a compelling need to engage in painstaking studies of how treatment decisions are made, including identifying the gatekeepers and determining how patient-clinician interactions influence decisions.”) (citation omitted).

18 See infra notes 22-44 and accompanying text.

19 See infra notes 71-77 and accompanying text.

20 See infra notes 95-98 and accompanying text.

21 See infra notes 48-58 and accompanying text.

22 See, e.g., Grimes v. Kennedy-Krieger Inst., Inc., 782 A.2d 807, 842-43 (Md. 2001) (involving research on lead paint abatement strategies in low-income housing occupied by children and allegations of racial and socioeconomic bias in subject selection); King, Patricia A., Race, Justice, and Research, in BEYOND CONSENT 91 (Kahn, Jeffrey P. et al. eds., 1998)Google Scholar (describing a government-funded measles vaccine trial in which most participants were African-American and parents were not told that the vaccine was experimental).

23 See Gilford, Allen L. et al., Participation in Research and Access to Experimental Treatments by HIV-Infected Patients, 346 NEW ENG. J. MED. 1373 (2002)Google Scholar; Stone, Valerie E. et al., Race, Gender, Drug Use, and Participation in AIDS Clinical Trials, 12 J. GEN. INTERNAL MED. 150, 153 (1997)Google Scholar (noting that, as of 1995, the incidence of HIV infection was six times higher in African-Americans and two times higher in Latinos than in whites, and concluding that women and patients of color were significantly less likely than whites to have participated in an AIDS clinical trial).

24 See Gilford et al., supra note 23, at 1375 (explaining that, because African-Americans accounted for thirty-seven percent of HIV cases, whites are overrepresented relative to incidence of disease in clinical trials of experimental HIV medications); id. at 1376-79 (noting that the disparities in clinical trial participation appeared within various socioeconomic strata and remained even after adjusting for level of education).

25 See Shavers et. al., supra note 5, at 233; Vital African American Recruitment Low in Prostate and Breast Cancer Drug Clinical Trials (NBC Nightly News television broadcast, Sept. 15, 2002), available at 2002 WL 3339803.

26 See Heiat, Asefah et al., Representation of the Elderly, Women, and Minorities in Heart Failure Clinical Trials, 162 ARCHIVES INTERNAL MED. 1682, 1684 (2002)Google Scholar (finding that only fifteen percent of patients enrolled in these studies were racial or ethnic minorities).

27 See Svensson, Craig K., Representation of American Blacks in Clinical Trials of New Drugs, 261 JAMA 263, 264 tbl. 1 (1989)Google Scholar.

28 Id. Moreover, the study did not suggest that African-Americans had a lower incidence of the diseases in question than other population groups overrepresented in the clinical trials. Id.

29 See id. at 264.

30 See DRESSER, supra note 3, at 64-65 (explaining that “the campaign to secure insurance reimbursement for trial participants’ patient care costs overlooks people with no insurance at all,” and observing that “remedying this injustice leaves intact the more widespread and serious difficulties faced by people who cannot afford standard care outside the research context”).

31 See id.

32 See id. at 51 (explaining that “insurers became unwilling to pay for such care, on the grounds that trial participants received interventions not established as safe and effective”).

33 See id.

34 See El-Sadr, Wafaa & Capps, Linnea, The Challenge of Minority Recruitment in Clinical Trials for AIDS, 267 JAMA 954, 956 (1992)Google Scholar (adding that “[p]hysicians have access to the most up-todate information regarding promising treatments and can thus guide their patients to a specific trial,” but warning that physicians “who practice in overcrowded and understaffed public clinics and hospitals … have neither the time nor the resources to seek out appropriate trials for their patients”).

35 See Stone, Valerie E. et al., Provider Attitudes Regarding Participation of Women and Persons of Color in AIDS Clinical Trials, 19 J. ACQUIRED IMMUNE DEFICIENCY SYNDROMES & HUMAN RETROVIROLOGY 245, 249 (1998)Google Scholar (describing a survey of providers in which twenty-five percent reported their belief that African-American patients would be less interested in clinical trials, fourteen percent believed Latino patients would have less interest and thirty percent believed Haitian patients would have less interest in AIDS clinical trial participation); cf. Christopher K. Daugherty, Commentary, HASTINGS CTR. REP., Sept.-Oct. 1996, at 20, 21 (arguing that physicians should tell patients about the availability of a clinical trial).

36 See El-Sadr & Capps, supra note 34, at 955 (explaining that “the primary interests of sponsors are the rapid completion of the trial and maximum adherence at minimum cost”).

37 See King, Talmadge E. Jr., Racial Disparities in Clinical Trials, 346 NEW ENG. J. MED. 1400, 1402 (2002)Google Scholar (explaining that these recruitment preferences result in a clinical trial population that “rarely mirrors the full spectrum of patients who are likely to receive the treatment”).

38 See id. at 1402; see also Stone et al., supra note 23, at 150.

39 See El-Sadr & Capps, supra note 34, at 956 (describing the Harlem AIDS Treatment Group and other Community Programs for Clinical Research on AIDS (CPCRA)).

40 See Comm. on Health Literacy, AMA Council on Scientific Aff., Health Literacy Report of the Council on Scientific Affairs, 281 JAMA 552, 553 (1999)Google Scholar (concluding that a variety of healthrelated materials, including discharge instructions, contraception instructions and consent forms, are written at levels well above the average patient's reading skills).

41 See id. at 552-53 (describing one large health literacy study that concluded that one-third of English-speaking patients at two public hospitals could not read or understand basic health materials and that forty-two percent of patients were unable to comprehend directions for taking medication on an empty stomach); see also Williams, Mark V. et al., Inadequate Functional Health Literacy Among Patients at Two Public Hospitals, 274 JAMA 1677, 1679-80 (1995)Google Scholar (finding that approximately thiry percent of English-speaking patients could not understand simple written health instructions and that over sixty percent of the patients in one study location could not read and comprehend a standard informed consent form). See generally Noah, Lars, The Imperative to Warn: Disentangling the “Right to Know” from the “Need to Know” About Consumer Product Hazards, 11 YALE J. ON REG. 293, 371-72 (1994)Google Scholar.

42 See Gazmararian, Julie A. et al., Health Literacy Among Medicare Enrollees in a Managed Care Organization, 281 JAMA 545, 549 tbl. 4 (1999)Google Scholar (concluding that nearly nineteen percent of whites had inadequate health literacy, compared with nearly thirty percent of English-speaking Hispanics, close to thirty-five percent of Spanish-speaking Hispanics, and approximately fifty-three percent of African-Americans).

43 See AMA Council, supra note 40, at 553.

44 In 1998, 9.8% of whites dropped out of high school, compared with 11.6% of African-Americans and 25% of Hispanics. U.S. DEPT. OF COMMERCE, STATISTICAL ABSTRACT OF THE UNITED STATES, tbls. 291, 292, 736 (2000). In the same year, 46% of whites were enrolled in college, compared with 35.8% of African-Americans and 23% of Hispanics. Id. In 1998, the median household income for whites was almost $41,000, compared with $25,351 for African-Americans and $28,330 for Hispanics. Id.; see also William P. O’Hare, America's Minorities—The Demographics of Diversity, POPULATION BULL., Dec. 1992, at 28-39 (describing educational and income disparities between the races).

45 See Stone et al., supra note 23, at 153-54.

46 See Eng, Thomas R. et al., Access to Health Information and Support: Public Highway or a Private Road?, 280 JAMA 1371 (1998)Google Scholar.

47 The Food and Drug Administration Modernization Act (FDAMA) amended the Public Health Service Act to require that NIH establish a publicly-accessible database on all clinical trials for drugs designed to treat serious or life-threatening conditions. See Pub. L. No. 105-115, § 113, 111 Stat. 2296 (1997) (codified at 42 U.S.C. § 282(j) (2000)); see also U.S. Nat’l Inst. of Health, Clinicaltrials.gov, at http://www.clinicaltrials.gov (providing resources and information about clinical research studies); Nat’l Cancer Inst., Cancer.gov at http://cancertrials.nci.nih.gov (informational site including, among others, articles on finding, conducting and understanding clinical trials). In addition, several privatelyfunded clinical trials databases provide information about clinical trials that focuses as much on recruiting participants as on conveying information. See, e.g., Musella Foundation, Clinical Trials and Noteworthy Treatments for Brain Tumors, at http://www.virtualtrials.org; CenterWatch, Clinical Trials Listing Service, at http://www.centerwatch.com. Private websites with names like “hopelink.com” and “emergingmed.com” also continue to proliferate. See Judith Newman, Drug Trials Reach out for Patients (and Vice Versa) on the Web, N.Y. TIMES, Feb. 27, 2001, at F5 (describing the rise of websites designed to help pharmaceutical and biotech companies locate patients afflicted with particular medical conditions for clinical trials).

48 See Shavers et al., supra note 5, at 234-35. Distrust in physicians engaged in research is not unique to the African-American population. After a series of well-publicized research injuries and deaths arising out of unethical physician/investigator conduct, many people of all races and ethnic backgrounds have begun to question the motives of the research establishment. See Tom Abate, Maybe Conflicts of Interest Are Scaring Clinical Trial Patients: Report That Blames Negative Media Also Cites Complaint Surge, S.F. CHRON., Apr. 30, 2001, at D1 (discussing a study that acknowledges a tenfold increase in complaints against clinical test sites and a growing concern about potential conflicts of interests); Ulysses Torassa, Putting Trials to the Test: After Asthma Study Death, Volunteers Weigh Risks, Benefits of Participating, S.F. CHRON., July 29, 2001, at B3 (describing the rise in recruitment of patients for clinical trials and the controversy associated with reports of deaths in clinical trials); see also Corbie-Smith, Giselle, Distrust, Race, and Research, 162 ARCHIVES INTERNAL MED. 2458, 2459-60 (2002)Google Scholar (concluding, however, that African-Americans were significantly more likely than whites to believe that their physicians would not fully disclose the risks of research participation); Frances Miller, H., Trusting Doctors: Tricky Business When It Comes to Clinical Research, 81 B.U. L. REV. 423 (2001)Google Scholar (describing several research injury incidents and advocating stronger rules prohibiting researcher conflicts of interest).

49 See King, supra note 22, at 95.

50 Tuskegee was among the first examples of research abuse to reach the public notice, but it was certainly not the last. Other examples include experiments involving injection of live cancer cells at the Jewish Chronic Disease Hospital in New York, experiments involving deliberate infection with viral hepatitis at the Willowbrook State School in New York, and the U.S. Army experiments with hallucinogenic compounds and radiation exposure. See JONATHAN D. MORENO, UNDUE RISK: SECRET STATE EXPERIMENTS ON HUMANS 53-85, 119-55, 189-94, 249-50 (2000) (describing these experiments).

51 See, e.g., FRED D. GRAY, THE TUSKEGEE SYPHILIS STUDY: THE REAL STORY AND BEYOND (1998); JAMES H. JONES, BAD BLOOD: THE TUSKEGEE SYPHILIS EXPERIMENT (1981); Curran, William J., The Tuskegee Syphilis Study, 289 NEW ENG. J. MED. 730 (1973)Google Scholar; Palmer, Larry I., Paying for Suffering: The Problem of Human Experimentation, 56 MD. L. REV. 604 (1997)Google Scholar; White, Robert M., Unraveling the Tuskegee Study of Untreated Syphilis, 160 ARCHIVES INTERNAL MED. 583 (2000)Google Scholar.

52 See JESSICA W. BERG ET AL., INFORMED CONSENT: LEGAL THEORY AND CLINICAL PRACTICE 255 (2001). Contrary to popular myth, however, none of those studied were deliberately infected with syphilis. Id.

53 See Shavers et al., supra note 5, at 234-35 (surveying approximately 200 people, nearly half of whom were African-American, and finding that eighty-one percent of those surveyed had prior knowledge of the Tuskegee study and that over half of them indicated that these events caused them to distrust medical researchers).

54 See Gilford et al., supra note 23, at 1379 (suggesting that more culturally sensitive methods of communication about research risks and benefits may help to dispel these beliefs); see also Corbie-Smith, Giselle et al., Attitudes and Beliefs of African Americans Toward Participation in Medical Research, 14 J. GEN. INTERNAL MED. 537, 540-41 (1999)Google Scholar (surveying African-Americans about their attitudes towards medical research, and quoting one participant as follows: “When you sign that paper, you sign all of your rights away because they have disclaimers all neatly typed up, reviewed by their lawyers to protect themselves from being sued”).

55 See Corbie-Smith et al., supra note 54, at 540; Gilford et al., supra note 23, at 1379; see also Sengupta, Sohini et al., Factors Affecting African-American Participation in AIDS Research, 24 J. ACQUIRED IMMUNE DEFICIENCY SYNDROMES 275 (2000)Google Scholar (concluding that distrust was the strongest predictor of African-Americans’ unwillingness to participate in AIDS research).

56 See Corbie-Smith et al., supra note 54, at 539-40; Shavers et al., supra note 5, at 234.

57 See El-Sadr & Capps, supra note 34, at 955 (elaborating on the details of informed consent necessary to conduct clinical trials).

58 Cf. Noah, Barbara A., The Invisible Patient, 2002 U. ILL. L. REV. 121, 135-47Google Scholar (book review) (making similar recommendations for enhanced communication between physicians and patients in regular therapeutic encounters).

59 See Corbie-Smith et al., supra note 48, at 2462 (“Community members become skeptical, and distrust possibly reinforced, when researchers approach communities only when recruiting subjects … . Engaging members of the target community, for example, through the mechanism of community advisory boards, can prove invaluable in the initial stages of study design, as well as in planning and evaluating recruitment strategies.”).

60 See NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research, 59 Fed. Reg. 14,508, 14,510 (Mar. 28, 1994) [hereinafter 1994 NIH Guidelines]. Interestingly, an article by a group of NIH clinical trial researchers responding to and interpreting the inclusion requirements in the guidelines focuses entirely on scientific issues and provides no commentary on or suggestions for implementing the minority recruitment and retention mandate. See Freedman, Laurence S. et al., Inclusion of Women and Minorities in Clinical Trials and the NIH Revitalization Act of 1993—The Perspective of NIH Clinical Trialists, 16 CONTROLLED CLINICAL TRIALS 277, 277-85 (1995)Google Scholar.

61 See Fouad, Mona N. et al., Statewide Tuskegee Alliance for Clinical Trials: A Community Coalition to Enhance Minority Participation in Medical Research, 91 CANCER 237 (2001)Google Scholar.

62 See id. at 237.

63 See Brown, David, Medicare to Pay for Experimental Treatments: Clinton Aims to Bring More Seniors into Clinical Trials, WASH. POST, June 8, 2000Google Scholar, at A9.

64 See Vasgird, Daniel R. et al., Protecting the Uninsured Research Subject, 6 J. PUB. HEALTH MGMT. PRACTICE 37, 40 (2000)Google Scholar.

65 See id. at 40.

66 See id. “The compensation given to individual subjects suffering from research-related injuries pales in comparison to the benefits gained by society when, for example, a new vaccine is proven to be beneficial. It follows that the failure to establish a requirement for research institutions to guarantee free medical coverage (should the need arise) would violate the ethical principle of beneficence.” Id.

67 See, e.g., Rebecca Dresser, Wanted: Single, White Male for Medical Research, HASTINGS CTR. REP., Jan.-Feb. 1992, at 24, 26-8 (arguing that decisions to exclude women and minorities from biomedical research reflect an assumption that white males are more deserving of the benefits that such research produces).

68 See DRESSER, supra note 3, at 82, 102 (describing organizations that represent women, African-Americans and other populations that advocate in favor of NIH research funding that will directly benefit their respective constituencies).

69 Many medical journals refuse to review articles for publication if the investigators of sponsors have retained publication veto power. See Davidoff, Frank et al., Sponsorship, Authorship, and Accountability, 286 JAMA 1232, 1233 (2001)Google Scholar.

70 See Karst, Kurt R., Comment, Pediatric Testing of Prescription Drugs: The Food and Drug Administration's Carrot and Stick for the Pharmaceutical Industry, 49 AM. U. L. REV. 739, 741 n.5 (2000)Google Scholar (citing estimates that as many as eighty percent of drugs on the market as of 1997 had not undergone testing in pediatric populations). The FDA sought to increase the clinical testing of drugs on pediatric patients where practical to do so. See Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological Products in Pediatric Populations, 62 Fed. Reg. 43,900 (Aug. 15, 1997) (requiring manufacturers of drugs that are widely used in pediatric populations but that do not contain adequate labeling information for these populations to submit evidence, in certain circumstances, to support dosage and administration directions for these patients), invalidated, Ass’n of Am. Physicians & Surgeons, Inc. v. FDA, 226 F. Supp. 2d 204 (D.D.C. 2002) (finding that the FDA exceeded its statutory authority by imposing regulations enabling it to withhold marketing permission in cases where the manufacturer has not tested the drug in pediatric populations).

71 Such studies frequently exclude children as well. Only forty-two percent of drugs that are routinely used to treat pediatric patients have been tested on children in clinical trials. See Pear, Robert, Drug Makers Face Order for New Pediatric Studies, N.Y. TIMES, Aug. 13, 1997, at A14Google Scholar.

72 See Scott, supra note 6, at 187-88; see also Alta Charo, R., Protecting Us to Death: Women, Pregnancy, and Clinical Research Trials, 38 ST. LOUIS U. L.J. 135 (1993)Google Scholar; Cotton, Paul, Is There Still Too Much Extrapolation from Data on Middle-Aged White Men?, 263 JAMA 1049 (1990)Google Scholar. The FDA's regulatory guidance on this issue revokes earlier guidances that excluded women of childbearing age from participation in early studies of drugs and concludes that exclusion of women is not medically necessary because appropriate precautions can prevent pregnancy and resultant fetal exposure to potentially toxic substances. See Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs, 58 Fed. Reg. 39,406, 39,408 (July 22, 1993) (recognizing also that “the early exclusion of women may have perpetuated, in a subtle way, a view of the male as the primary focus of medicine and drug development”). One might make a similar argument about the exclusion of minority participants from clinical research.

73 See Cotton, Paul, Examples Abound of Gaps in Medical Knowledge Because of Groups Excluded from Scientific Study, 263 JAMA 1051 (1990)Google Scholar.

74 See, e.g., Svensson, supra note 27, at 265 (concluding that investigators do not adequately account for racial differences as a source for variability in drug research results and that insufficient data exist to assess the safety and efficacy for the African-American population of many drugs currently on the market); Yancy, Clyde W. et al., Race and the Response to Adrenergic Blockade with Carvedilol in Patients with Chronic Heart Failure, 344 NEW ENG. J. MED. 1358, 1362-64 (2001)Google Scholar; Zhou, Hong-Hao et al., Racial Differences in Drug Response: Altered Sensitivity to and Clearance of Propanolol in Men of Chinese Descent as Compared with American Whites, 320 NEW ENG. J. MED. 565 (1989)Google Scholar (concluding that Chinese men have greater sensitivity than white men to the effects of the drug on heart rate and blood pressure); Joint Nat’l Comm. on Detection, Evaluation, and Treatment of High Blood Pressure, The 1984 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, 144 ARCHIVES INTERNAL MED. 1045, 1057 (1985) (noting that, although African-Americans suffer from a higher incidence of hypertension, ACE inhibitors are less effective in treating this condition among African-Americans than in the white population).

75 See Svensson, supra note 27, at 265 (“If a subset of the population is underrepresented or excluded from … trials, important information on the proper use of drugs in that subset will be unavailable.”). See generally LARS NOAH & BARBARA A. NOAH, LAW, MEDICINE, AND MEDICAL TECHNOLOGY: CASES AND MATERIALS (2002).

76 See Dresser, supra note 67, at 26 (describing a study in which the “normal” dosage of Lithium for white males was found to be frequently toxic for African-American patients).

77 See Noah, Lars, Informed Consent and the Elusive Dichotomy Between Standard and Experimental Therapy, 28 AM. J.L. & MED. 361 (2002)Google Scholar.

78 See Schwartz, Robert S., Racial Profiling in Medical Research, 344 NEW ENG. J. MED. 1392, 1393 (2001)Google Scholar (discussing the “fallacy of race as a scientific concept and the dangers inherent in practicing race-based medicine”). The controversy about the use of racial categories extends far beyond health research. In the most recent U.S. Census, for example, some conservative political organizations opposed certain methodologies dealing with racial categories and some civil rights organizations debated the addition of a “multiracial” category to the Census process. See Pomeroy, Lisa K., Comment, Restructuring Statistical Policy Directive No. 15: Controversy over Race, 32 U. TOL. L. REV. 67, 67–69 (2000)Google Scholar.

79 In fact, there is more variation within racial groups than between them. See Kiefe, Catarina I., Race/Ethnicity and Cancer Survival: The Elusive Target of Biological Differences, 287 JAMA 2138, 2138 (2002)Google Scholar (“Most measurable human traits exhibit more variability across rather than within races … . Therefore, over the past several decades, race as a biological construct became largely discredited among scientists, in favor of race as a sociologic construct, based not on biology but rather on culture, social environment, history … .”); see also KWAME ANTHONY APPIAH, IN MY FATHER's HOUSE 32-38 (1992) (arguing that there is no biological basis for race); JOSEPH L. GRAVES, JR., THE EMPEROR's NEW CLOTHES: BIOLOGICAL THEORIES OF RACE AT THE MILLENIUM 155-56 (2001); Freeman, Harold P., The Meaning of Race in Science—Considerations for Cancer Research, 82 CANCER 219 (1998)Google Scholar; Hickman, Christine B., The Devil and the One Drop Rule: Racial Categories, African Americans, and the U.S. Census, 95 MICH. L. REV. 1161, 1241 (1997)Google Scholar (quoting with approval Professor Haney-Lopez: “I define a race as a vast group of people loosely bound together by historically contingent, socially significant elements of their morphology and/or ancestry”).

80 See Rick Weiss, Life's Blueprint in Less than an Inch: Only a Small DNA Segment Makes a Human, WASH. POST, Feb. 11, 2001, at A1. In a fascinating twist along this promising trail of medical discovery, scientists are now debating the ethical problems with mapping racial variations that predispose certain populations to particular diseases such as cancer, diabetes and schizophrenia. See Nicholas Wade, Genome Mappers Navigate the Tricky Terrain of Race, N.Y. TIMES, July 20, 2001, at A17. Conversely, some commentators have criticized both the genetically and socially constructed definitions of disease. See Noah, Lars, Pigeonholing Illness: Medical Diagnosis as a Legal Construct, 50 HASTINGS L.J. 241 (1999)Google Scholar.

81 See Guterman, Lila, Shades of Doubt and Fears of Bias in the Doctor's Office, CHRON. HIGHER EDUC., May 25, 2001Google Scholar, at A16 (explaining that critics of studies designed to understand connections between race and drug efficacy “accuse the researchers of suggesting that biological differences underlie, and therefore reinforce, the social concept of race, implying genetic differences that may not even exist”); Witzig, Ritchie, The Medicalization of Race: Scientific Legitimization of a Flawed Social Construct, 125 ANNALS INTERNAL MED. 675, 676 (1996)Google Scholar (arguing that “[a]mple scientific evidence repudiates the use of social constructs of race” and that “medical workers should know that most variation occurs between individual persons”).

82 See Satel, Sally, I Am a Racially Profiling Doctor, N.Y. TIMES MAG., May 5, 2002Google Scholar, at 56, 57.

83 See, e.g., NIH, Draft Strategic Research Plan to Reduce and Ultimately Eliminate Health Disparities, Fiscal Years 2002-2006, at 2-3 (Oct. 6, 2000), available at http://www.nih.gov (describing coordinated research plans to “strengthen and expand research on the epidemiology and risk factors related to a variety of diseases and conditions that disproportionately affect minority populations,” and noting that “[t]hese disparities are believed to be the result of the complex interaction among biological factors, the environment, and specific health behaviors”).

84 See Exner, Derek V. et al., Lesser Response to Angiotensin-Converting-Enzyme Inhibitor Therapy in Black as Compared with White Patients with Left Ventricular Dysfunction, 344 NEW ENG. J. MED. 1351, 1355-57 (2001)Google Scholar; Kuehl, Peter et al., Sequence Diversity in CYP3A Promoters and Characterization of the Genetic Basis of Polymorphic CYP3A5 Expression, 27 NATURE GENETICS 383, 388-89 (2001)Google Scholar; Wandel, Christoph et al., CYP3A4 Activity in African American and European American Men: Population Differences and Functional Effect of the CYP3A4*1B 5’-Promoter Region Polymorphism, 68 CLINICAL PHARMACOLOGY & THERAPEUTICS 82 (2000)Google Scholar; Xie, Hong-Guang et al., Molecular Basis of Ethnic Differences in Drug Disposition and Response, 41 ANNUAL REV. PHARMACOLOGY & TOXICOLOGY 815 (2001)Google Scholar.

85 See Winslow, Ron, Pharmacia Drug Holds Promise for Blacks with Hypertension, WALL ST. J., June 11, 2002Google Scholar, at D4 (describing a comparative drug study that identified a product that more effectively reduced hypertension in African-Americans than a commonly-prescribed ARB).

86 Id.

87 One psychiatrist describes her practice of starting her African-American patients on lower doses of antidepressants because research shows that slower metabolism of these drugs is more common among members of this group and because she wishes to avoid unpleasant side effects that would cause her patients to abandon the drug therapy altogether. Satel, supra note 82, at 58 (“Admittedly, race is a rough marker … [y]et an imprecise clue is better than no clue at all.”).

88 See Roses, Allen D., Pharmacogenetics and the Practice of Medicine, 405 NATURE 857 (2000)Google Scholar.

89 For a far more detailed treatment of the scientific and regulatory issues associated with pharmacogenomics, see Noah, Lars, The Coming Pharmacogenomics Revolution: Tailoring Drugs to Fit Patients’ Genetic Profiles, 43 JURIMETRICS J. 1 (2002)Google Scholar.

90 See Wood, Alastair J.J., Racial Differences in the Response to Drugs: Pointers to Genetic Differences, 344 NEW ENG. J. MED. 1393, 1395 (2001)Google Scholar (“[A]n increased specificity of therapies is likely to increase the differences in response among persons of different genetic backgrounds.”).

91 See Rothstein, Mark A. & Epps, Phyllis Griffin, Ethical and Legal Implications of Pharmacogenomics, 2 NATURE REVIEWS: GENETICS 228, 230 (2001)Google Scholar (“As clinical trials increasingly consist of genetically non-diverse groups, policy makers will need to consider whether to expand the concepts underlying orphan drug policies to stimulate research into and the development of drugs for populations who, by virtue of their genetic make-up, face inequities in drug development efforts.”); Rick Weiss, The Promise of Precision Prescriptions, WASH. POST, June 24, 2000, at A1 (“One fear is that profit-conscious pharmaceutical companies will use pharmacogenomics to aim their drug development efforts toward genetic subgroups of people who can best afford to pay for them, further marginalizing already undeserved minorities.”). Similarly, drug manufacturers have left the vaccine business because this market offers relatively low financial returns. See Noah, Lars, Triage in the Nation's Medicine Cabinet: The Puzzling Scarcity of Vaccines and Other Drugs, 54 S.C. L. REV. 371 (2002)Google Scholar.

92 See Noah, supra note 89, at 12 (“At present, when clinical trials produce equivocal results, sponsors may engage in statistical analyses designed to stratify the subject population in the hopes of identifying some subset in whom the investigational product worked without causing unacceptable side effects. Pharmacogenetics could replace this brute force method with a more refined biological tool for making such cuts earlier in the process.”).

93 See Ahluwalia, Jasjit S. et al., Sustained-Release Bupropion for Smoking Cessation in African Americans, 288 JAMA 468 (2002)Google Scholar (confirming the effectiveness of bupropion for smoking cessation among African-Americans); Benowitz, Neal L., Smoking Cessation Trials Targeted to Racial and Economic Minority Groups, 288 JAMA 497 (2002)Google Scholar (explaining that the trials are designed to evaluate whether behavioral interventions to assist in smoking cessation that were developed for white, middle-class smokers work as effectively for people in different racial groups or with lower incomes); McNamara, Damian, Fixed-dose Lotrel Further Lowered Blood Pressure in LOGIC, 35 INTERNAL MED. NEWS 37 (2002)Google Scholar (describing a study that concluded that a combination therapy led to further blood pressure reductions in African-Americans); Ronald Rosenberg, Firm to Test Heart Drug for Blacks, BOSTON GLOBE, Mar. 10, 2001, at F1 (describing a study to test a heart failure therapy exclusively in African-Americans to determine whether the drug will improve heart function in the study group which generally responds less well than whites to other approved heart failure therapies).

94 The Belmont Report represents the conclusions of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission was charged with identifying the basic ethical principles that should govern the conduct of medical research involving human subjects, including the risk-benefit assessment process, guidelines for the selection of human subjects and informed consent issues. The Belmont Report summarizes these basic ethical principles as identified by the Commission in a four-day meeting in February 1976 at the Smithsonian Institution's Belmont Conference Center. See Protection of Human Subjects, 44 Fed. Reg. 23,192, 23,194 (Apr. 18, 1979) [hereinafter Belmont Report].

95 See NIH, Special Instructions to Applicants Using Form PHS 398 Regarding Implementation of the NIH/ADAMHA Policy Concerning Inclusion of Women and Minorities in Clinical Research Study Populations (1990), available at http://www.nih.gov.

96 See 1994 NIH Guidelines, supra note 60, at 14,508 (adding that the updated policy is intended to “address significant gaps in knowledge about health problems that affect women and racial and ethnic minorities and their subpopulations”). When inclusion of these groups would be scientifically inappropriate or when data already exists that documents no significant difference between the effects of the studied interventions on these different groups, however, the guideline provides an exception to these requirements. See id.

97 See Investigational New Drug Applications and New Drug Applications, 60 Fed. Reg. 46,794 (Sept. 8, 1995) (to be codified at 21 C.F.R. pts. 312 & 314) (proposing a rule that would require manufacturers seeking new drug approval to submit safety and efficacy data reflecting breakdown according to gender, age and racial subgroups (in addition to aggregate data), but that would not require inclusion of these groups in clinical trials); Sherman, Linda A. et al., Women in Clinical Trials: An FDA Perspective, 269 SCIENCE 793, 795 (1995)Google Scholar (“[T]he FDA expects sponsors to study the full range of patients likely to receive a drug, including both genders, and to analyze the data to determine whether responses in various groups are different.”); see also Noah, Lars, Constraints on the Off-Label Uses of Prescription Drug Products, 16 J. PRODS. & TOXICS LIAB. 139, 139-47 (1994)Google Scholar (describing the prevalence of off-label prescribing by physicians, necessitated by limitations in clinical testing, and the FDA's regulatory responses).

98 See Food and Drug Administration Modernization Act, Pub. L. No. 105-115, § 115, 111 Stat. 2296, 2313 (1997) (codified at 21 U.S.C. § 355(b)(1) (2000)) (“The Secretary shall, in consultation with the Director of the National Institutes of Health and with representatives of the drug manufacturing industry, review and develop guidance, as appropriate, on the inclusion of women and minorities in clinical trials required” for new drug approval). Also, the agency has attempted to work with international bodies to harmonize its approach to understanding the effect of “ethnic factors” in foreign clinical data. See Int’l Conference on Harmonisation, Guidance on Ethnic Factors in the Acceptability of Foreign Clinical Data, 63 Fed. Reg. 31790, 31791 (June 10, 1998) (“The purpose of this guidance is to facilitate the registration of medicines … by recommending a framework for evaluating the impact of ethnic factors upon a medicine's effect … .”).

99 Two overlapping sets of federal regulations, promulgated by the FDA and the predecessor of HHS, now govern human subjects research. The FDA regulations apply to all human subjects research involving articles such as drugs, medical devices and biological products that will eventually support a licensing application. See 21 C.F.R. § 50.1 (2002). The HHS regulations cover all research conducted or supported by a federal agency. See 45 C.F.R. § 46.101 (2002). Many sections of these regulations are nearly identical. This Article will cite the HHS regulations except in cases where the FDA regulations differ significantly; in those cases, both sets of regulations will be cited.

100 In brief, the regulations require that the study design minimize the risks to the subjects by using sound research procedures and, in the case of therapeutic research, by preferring procedures that typically would comprise standard diagnostic tests or treatment. 45 C.F.R. § 46.111(a)(1). In addition to ensuring that risks to subjects are minimized, the IRB must consider whether those risks, whatever their magnitude, are reasonable in relation to the probable benefits to the subjects and the importance of the anticipated scientific knowledge. See id. § 46.111(a)(2). The IRB thus must weigh potential risks and benefits to subjects associated with participation in the research. See id. (“In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from the risks and benefits of therapies subjects would receive even if not participating in the research).”).

101 See id. §§ 46.111(a)(4)-(5), 46.116.

102 See id. § 46.111(b). The federal research regulations do not, of course, reach research conducted in foreign countries, though other international standards on medical research such as the Nuremberg Code and the Declaration of Helsinki serve to protect foreign research subjects. Commentators strongly criticized overseas trials on maternal-fetal AIDS transmission using a placebo control because these trials violate basic international principles of human subjects protections. For more on the international dimensions of human subjects protections and vulnerable populations, see Todres, Jonathan, Can Research Subjects of Clinical Trials in Developing Countries Sue Physician-Investigators for Human Rights Violations?, 16 N.Y.L. SCH. J. HUM. RTS. 737 (2000)Google Scholar; Varmer, Harold & Satcher, David, Ethical Complexities of Conducting Research in Developing Countries, 337 NEW ENG. J. MED. 1003 (1997)Google Scholar.

103 Federal Policy for the Protection of Human Subjects, 56 Fed. Reg. 28,003, 28,010 (June 18, 1991).

104 Id. (“In exercising their responsibilities, IRBs are charged with evaluating the benefits and burdens of research so that unjust social patterns do not appear in the overall distribution of the burdens and benefits of research.”). On the use of preambles to interpret regulations, see Noah, Lars, Diving Regulatory Intent: The Place for a “Legislative History” of Agency Rules, 51 HASTINGS L.J. 255 (2000)Google Scholar.

105 Belmont Report, supra note 94, at 23,197.

106 See Nat’l Bioethics Advisory Comm’n, Ethical and Policy Issues in Research Involving Human Participants 4 (2001), available at http://www.georgetown.edu/research/nrcbl/nbac/human/oversumm.html (“Calling competent people intrinsically ‘vulnerable’ can be both insulting and misleading. It is not their gender or other group designation that exposes them to injury or coercion, but rather their situation that can be exploited by ethically unacceptable research.”).

107 See BERG ET AL., supra note 52, at 271.

108 See 45 C.F.R. § 46.111(a)(4)-(5) (2001). Both sets of regulations demand essentially identical elements in the disclosure of research procedures and risks to potential participants, including a description of the procedures to be followed and identification of any procedures which are experimental, a description of any reasonably foreseeable risks or discomforts to the subject, a description of any benefits to the subject or to others, a discussion of alternative procedures or courses of treatment, if any, that might be advantageous to the subject, and a statement that participation is voluntary and that the subject may discontinue participation at any time without penalty. Id. § 46.116(a).

109 See id. § 46.116 (providing that the “investigator shall seek … consent only under circumstances that provide the prospective subject … sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence”). Despite the fact that many IRBs have interpreted the “language understandable to the subject” clause in this rule to require informed consent forms to be written at an eighth grade reading level, comprehension problems remain. See id.; see also Paasche-Orlow, Michael K. et al., Readability Standards for Informed-Consent Forms as Compared with Actual Readability, 348 NEW ENG. J. MED. 721, 723-24 (2003)Google Scholar (providing examples of informed consent text at a variety of reading levels and concluding that most medical schools did not comply with their own internal readability requirements).

110 See id. § 46.111(a)(4)-(5).

111 See 21 C.F.R. § 50.23 (2002).

112 See FDA, Protection of Human Subjects: Informed Consent, 60 Fed. Reg. 49,086, 49,093 (Sept. 21, 1995).

113 See BERG ET AL., supra note 52, at 271.

114 See Corbie-Smith, supra note 48, at 2460 (explaining that both lower educational attainment and unemployment were associated with higher degrees of distrust in medical research).

115 See 45 C.F.R. § 46.116 (2002).

116 See Dickert, Neal & Grady, Christine, What's the Price of a Research Subject? Approaches to Payment for Research Participation, 341 NEW ENG. J. MED. 198 (1999)Google Scholar. Payments may include non-monetary incentives as well. Recently, some protocols to test drugs in pediatric populations have offered gift certificates to toy stores in addition to cash and free study medications. See Rachel Zimmerman, Desperately Seeking Kids for Clinical Trials, WALL ST. J., May 29, 2002, at D1. IRBs also worry about coercion in the form of catchy but potentially misleading trial acronyms, such as BRAVO, GUSTO, the EMERALD study and PROVE IT. Berkwits, Michael, Capture! Shock! Excite! Clinical Trial Acronyms and the “Branding” of Clinical Research, 133 ANNALS INTERNAL MED. 755, 757-59 (2000)Google Scholar.

117 See HHS, Recruiting Human Subjects: Pressures in Industry-Sponsored Clinical Research, (2000), available at http://www.researchrountable.com/oigreports.htm (describing and criticizing current trends in research subject recruitment, including enrollment incentives to physicians and patientdirected advertising that promotes the therapeutic misconception).

118 Id. at 16-28.

119 See DRESSER, supra note 3, at 65; Dickert & Grady, supra note 116, at 198.

120 The HHS regulations do not address the issue of payment, and the OHRP and FDA guidelines on the subject leave the controversy unresolved, noting, unhelpfully, that “[t]he IRB should review both the amount of payment and the proposed method of timing of disbursement to assure that neither are coercive or present undue influence.” FDA, Guidance for Institutional Review Boards and Clinical Investigators (1998), available at http://www.fda.gov/oc/ohrt/irbs/toc4.html#payment. Nevertheless, the research community, patient advocates and ethicists appear to agree on some basic principles, such as preferring payments that compensate for travel expenses and lost time at work but that are not so large as to be unduly influential, and requiring payments to be pro-rated should a research participant choose to leave the protocol before its completion. Id.

121 See BERG ET AL., supra note 52, at 272; see also Vasgird et al., supra note 64, at 40 (“In high-risk studies, a large number of research subjects come from a population composed primarily of individuals from lower socioeconomic backgrounds. These individuals are ‘often chronically ill’ and are either uninsured or underinsured, and the frequency of their participation may be attributed to their necessity to utilize whatever health benefits are offered in the study to substitute for the lack of regular care.”).

122 See BERG ET AL., supra note 52, at 272.

123 The regulation elaborates as follows: “In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.” 45 C.F.R. § 46.111(a)(3) (2002).

124 See Belmont Report, supra note 94, at 23,196.

125 See Emanuel, Ezekial J. et al., What Makes Clinical Research Ethical?, 283 JAMA 2701, 2704 (2000)Google Scholar.

126 See id. At the same time, researchers must refrain from recruiting or enrolling individuals who might be eligible to participate based on the scientific objectives of the research, but who may be at greater risk of injury due to age or co-existing medical conditions. Id. at 2705. Because the rates of some diseases and conditions are disproportionately high among members of racial and ethnic minority groups, some individuals in these groups may be barred from participation due to co-existing illness.

127 See id. at 2705. The debate surrounding the appropriate subject selection criteria for testing HIV vaccines provides an interesting vehicle for considering these issues. See Grushcow, Jeremy, The Ethics of Subject Selection for Testing Live-Attenuated HIV Vaccines, 6 U. CHI. L. SCH. ROUNDTABLE 113, 117 (1999)Google Scholar (exploring the ethical difficulties with testing the vaccine on three proposed populations—physicians, terminal cancer patients and citizens of developing countries—and concluding that only citizens of developing countries with high rates of HIV infection may be appropriate subjects for such testing).

128 See 45 C.F.R. § 46.101(a).

129 Cf. DRESSER, supra note 3, at 82-84 (discussing an “affirmative action” approach to funding research into diseases affecting primarily women or underrepresented minority groups).

130 Some IRBs require investigators to provide a justification for the exclusive enrollment of any racial or ethnic population. See, e.g., Univ. of Fla., Institutional Review Board Introductory Questionnaire, available at http://irb.ufl.edu/irb01/forms.htm.

131 See 1994 NIH Guidelines, supra note 60, at 14,510.

132 See 21 C.F.R. § 56.107(b); 45 C.F.R. § 46.107(b).

133 21 C.F.R. § 56.107(a); 45 C.F.R. § 46.107(a). The regulations also urge IRBs that regularly review research involving vulnerable categories of subjects to include members “who are knowledgeable about and experienced in working with those subjects.” See id. To the extent that the regulations on vulnerable subjects have been interpreted to include special consideration for minorities participating in research, this provision might be read to provide further support for including minority IRB members, but to date this is not a requirement. See Nat’l Bioethics Advisory Comm’n, supra note 106, at 12 (recommending that IRBs should include “members who represent the perspectives of participants, members who are unaffiliated with the institution, and members whose primary concerns are in nonscientific areas” and that for “purposes of both overall membership and quorum determinations these persons should collectively represent at least 25 percent of the [IRB] membership”).

134 Cf. Nat’l Bioethics Advisory Comm’n, supra note 106, at 10-11 (recommending mandated general research education for all IRB members, staff and clinical investigators).

135 See Arthur L. Caplan, Is There a Duty to Serve as a Subject in Biomedical Research?, IRB, Sept.-Oct. 1984, at 1. Of course, such a requirement might exacerbate inequalities. In the military context, this country has witnessed a different trajectory: minorities underrepresented in the armed forces through the mid-twentieth century, but then overrepresented among soldiers asked to risk their lives to serve the common good.

136 See GEORGE ANNAS ET AL., INFORMED CONSENT TO HUMAN EXPERIMENTATION: THE SUBJECT's DILEMMA 257-77 (1977); ROBERT J. LEVINE, ETHICS AND REGULATION OF CLINICAL RESEARCH 118-23 (1981); Nat’l Bioethics Advisory Comm’n, Ethical and Policy Issues in Research Involving Human Participants 124 (2001), available at http://www.georgetown.edu/research/nrcbl/nbac/pubs.html; Adams, Bernard R. & Shea-Stonum, Marilyn, Toward a Theory of Control of Medical Experimentation with Human Subjects: The Role of Compensation, 25 CASE W. RES. L. REV. 604, 637-47 (1975)Google Scholar.