A Legacy of Mistrust: Research and People of Color
Clinical trials (the study of new treatments in people) are critical if we are ever to find better ways to treat HIV, and, eventually, a cure. Unfortunately, people of color, women, and IV drug users have been under-represented in these trials for many years. In fact, research for many diseases has often focused on white men, leading to a dangerous lack of data on how treatments work in women and people of color. Why has this occurred? To understand the challenges of encouraging participation by those who have often been overlooked, we must be aware of previous violations of human rights in clinical trials.
The Legacy of Tuskegee
One such notable violation was the Tuskegee Syphilis Study, which began in 1932 in Alabama but continued for 40 years until it was publicly exposed in the New York Times in 1972. Researchers observed the progression of syphilis in hundreds of poor black men who were unaware of their disease and who had not given their informed consent. The most tragic aspect of the study was that even after penicillin was found to cure syphilis in 1940, these men were denied access to it. As a result, many of them died or developed serious complications, including the irreversible neurological effects of end-stage syphilis.
The study's long duration and its clearly unethical design make it one of the most tragic episodes in public health. In communities of color, it has led to a long-lasting mistrust of research, the government and of the medical profession as a whole.
The study's public exposure led to Congressional hearings and the National Research Act in 1974, which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission established protective regulations for those viewed as vulnerable to exploitation, including children, mentally retarded individuals, prisoners, and minorities.
Despite this legislation and the creation of organizations whose purpose is to improve the recruitment of minorities into clinical trials, barriers remain, both from patients and researchers. For example, African Americans were initially excluded from a clinical trial of a new treatment for hepatitis C, because they are less likely to respond to current treatments and might affect the study results. Following pressure by advocacy groups, 15 African Americans were included in the study -- a number too small to provide meaningful findings.
Women and Thalidomide
The history of regulations regarding women in trials -- particularly pregnant women or women of childbearing age -- is complicated, in part because of the thalidomide tragedy. Thalidomide had been used in Germany as an anti-nausea drug for pregnant women since 1956, but in 1962 it was withdrawn when more than 10,000 babies worldwide were born with deformities after their mothers took it. The most prominent U.S. response was the 1962 "Kefauver Amendments" that made it mandatory for drug companies to prove the effectiveness of their drugs to the FDA. The amendments also required drugs to undergo animal studies and human trials, including trials in pregnant women, to ensure a drug's safety. But in 1977, amid growing concern about the harm caused to fetuses when testing new drugs in pregnant women, the FDA created a policy excluding even potentially pregnant women from clinical trials.
But the resulting low number of women in clinical trials eventually led to laws to encourage their participation. For example, the inclusion of women improved after the flawed 1982 "Aspirin Study" (which included only men) found that aspirin could lower the risk of heart attack. But since there were no women in the study, doctors were faced with the dilemma of how to apply the results to them. As a result, Congress passed the NIH Revitalization Act of 1993 to guarantee that women and minorities were included in clinical research.
Even though the struggle to push forward the women's health agenda helped pave the way for minority health rights, there are still significant challenges to the inclusion of minorities in research. The legacy of Tuskegee, the mistrust of the medical establishment, unequal access to care, lack of awareness of clinical trials, and inadequate involvement of minority researchers are just some of the obstacles we must confront.
Although patient mistrust of the medical system is often cited as a barrier to enrolling minorities in clinical trials, distrust of medical researchers by minority physicians has also been found to be an important barrier. Studies have found that although the level of trust in medical researchers is greater than that found in patients, an ethnic community difference may exist. This mistrust is a major contributing factor to the lack of patient referrals to clinical trials, and has been found to be related to the physicians' previous experience with clinical trials.
The National Medical Association, an organization of African-American physicians, founded Project IMPACT (Increase Minority Participation and Awareness of Clinical Trials) in an effort to improve minority involvement in clinical trials. One of the primary aims of the project is to increase the involvement of minority physicians in clinical trials by identifying barriers and offering education to physicians. In 2008, 200 African-American physicians were asked about their involvement in clinical research. The survey showed that their participation was generally low -- less than 25%. Their participation in clinical research during medical school, residency, and fellowships was also low. Reasons included a lack of time, lack of patients that fit the study criteria, and lack of a study coordinator or information management systems.
In order to increase their involvement as investigators in clinical trials, formal education workshops were offered by Project IMPACT to the physicians who had completed the survey. A total of 84 individuals participated. The most common reason given for participation was to gather information on clinical trials and the belief that participation would increase opportunities to become involved. After attending the workshops, almost 20% reported that they became involved with a clinical trial. Although this was not a large increase, the attitudes of the majority (68%) toward clinical trials were more positive after participating.
Including minorities in clinical trials is particularly important in HIV prevention trials, as minorities account for most new HIV cases in the U.S. In 1999, the NIH Division of AIDS established the HIV Prevention Trials Network (HPTN) to develop and test non-vaccine methods to prevent HIV transmission through a worldwide clinical trial network.
A 2004 HPTN study, Explore, studied the use of various counseling strategies to reduce HIV acquisition and risky sexual behaviors. Special planning sessions were held to assist sites improve recruiting of minorities. For example, study materials were translated to ensure that language was not a barrier. Even so, not all sites had equal success in recruiting minorities. Future HPTN studies need to focus on increasing the retention of younger men of color, especially men who engage in high-risk behavior. This may be challenging, since they may have lifestyles or values that are at odds with the intervention being studied.
HPTN recommends that any research effort should include community advisors to help design methods that will improve recruitment of minorities. Studies have shown that research interventions are most likely to succeed when everyone involved -- investigators, agencies, manufacturers, and community members -- sees the research as relevant and the process as collaborative. HPTN also states that community members should play an integral role in the development of trials in their community. To ensure this, HPTN has created several working groups and resources.
The Community Working Group advocates for community participation at all levels of the research process and ensures community participation. The Regional Working Groups in Africa, Eurasia, and the Americas provide an opportunity for community representatives and site staff to work with other sites in their region. Community Activities & Research Staff should be included at every site to support community involvement, as should Community Educators. A variety of resources for community educators should be available. For example, the Community Involvement Toolbox includes internet resources and printed pamphlets to support efforts for community participation. Finally, the CORE Community Involvement Program manages community participation processes. Its staff provide technical assistance and other mechanisms for sharing information throughout the HPTN.
Addressing the greater impact of HIV on minorities requires a robust research agenda designed to shed light on the reasons for their vulnerability and identify new prevention strategies. The success of these studies will rely on the support of and partnerships with the communities involved. Studies that focus on minority groups must include specifically designed strategies for community involvement aimed at closing the historic shortage of minority involvement in trials.
The lessons we have learned from history make it clear that to correct past wrongs, trials need to make alliances within the communities in which the studies are carried out. These alliances require the inclusion of programs within each trial specifically designed to establish a connection with the community. Only through such collaboration can we overcome the chronic disparities in health.
Cynthia Santos is a third-year medical student at Weill Cornell Medical School.
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