This exploratory study provides an in-depth and multifaceted look at the ethical concept of vulnerable populations from the perspectives of researchers involved in HIV/AIDS clinical trials. A conceptual framework was developed that illustrates a combination of vulnerable population characteristics/categories identified from the broad definitions in the Common Rule (e.g., based on socioeconomics), and in prior reviews about HIV-infected and HIV-affected populations [9
], but organizes them to show possible circumstances in which HIV/AIDS clinical trial enrollees could be considered vulnerable in clinical research, and for which special protections could be warranted (e.g., consent monitoring in cases where there is educational, cognitive, or treatment-related vulnerabilities). In addition, barriers posed by Subparts B, C, and D of 45 CFR 46 were explored in the context of HIV/AIDS clinical trials, further demonstrating that applying group-based vulnerability can result in unnecessary exclusion of individuals in the vulnerable population categories of pregnant women/fetuses, prisoners, and children. The study’s findings are consistent with concerns from bioethicists that vulnerability in research has not been clearly or uniformly defined in the federal regulations on human subjects research, and special protections delineated for select vulnerable populations often have made it difficult for these vulnerable populations to participate in HIV/AIDS clinical trials from which they could benefit [2
First, the study supports prior recommendations to look at vulnerability as situational, rather then group-based, as is typically used by IRBs in the United States and internationally [3
]. At a practical level, we hope that AACTG, PACTG, and HPTN researchers could use the conceptual framework as a guide to identify areas of vulnerability within their respective clinical trial populations, and implement appropriate protections to their informed consent process and/or recruitment procedures. Furthermore, we believe that the factors comprising the conceptual framework are not necessarily distinct to HIV/AIDS and may broaden the conceptual framework’s potential to understanding vulnerable populations for other diseases or conditions, or that are distinct to minority groups (e.g., being undocumented). At an institutional level, we hope that local IRBs could use this conceptual framework to expand their thinking about what makes subjects vulnerable in HIV/AIDS clinical trials, and to consider innovative and alternative ways in which researchers could implement additional protections for clinical trial participants with one or more vulnerabilities.
Second, understanding the concerns among HIV researchers on why pregnant women, prisoners, and children should not be considered vulnerable for all types of clinical research strengthens the argument to examine vulnerability as situational. At an institutional level, we hope that these findings could encourage local IRBs to think of these three vulnerable populations more on a case-by-case basis, particularly in situations where clinical trial participants who represent these vulnerable populations stand to benefit from the results of the research.
This study has two main limitations. For the investigator/study coordinator sample, the response rate of 42% at the site level was low even though all 65 sites (31 AACTG, 18 PACTG, 16 HPTN) were asked to participate. Given that we were unsuccessful in interviewing PIs, other investigators, or study coordinators from 38 of the sites, our conceptual framework may be missing other important factors that contribute to vulnerability in clinical research. This is particularly true for PACTG that may have other vulnerable population indicators more relevant when conducting clinical trials with children (and adolescents). Second, the conceptual framework for vulnerable populations in HIV/AIDS clinical trials is missing the perspectives coming from HIV/AIDS clinical trial enrollees with respect to how they consider themselves vulnerable. Future research may be useful to better explore vulnerability in clinical research from the enrollees’ perspective.
In conclusion, the debate over vulnerable populations usually happens among bioethics scholars with little or no input from biomedical researchers about what they think, including if they agree with the current definitions, and their concerns with IRB regulations associated with vulnerable populations. The conceptual framework for understanding vulnerable populations in HIV/AIDS clinical trials was developed in this study from the perspectives of HIV/AIDS researchers to help us move beyond the broad categories of “economically,” “educationally,” or “decisionally” impaired, or the narrowly focused vulnerable categories of pregnant women, prisoners, and children for which there are special protections in 45 CFR 46. Indeed, the conceptual framework illustrates other plausible relationships of vulnerability, and this study’s participants also identified interventions to address certain types of vulnerability, to which IRBs should pay greater attention. Future work on understanding vulnerable populations could expand the conceptual framework to include vulnerable population indicators for other diseases or conditions, and the conceptual framework could be used as a guide to develop interventions that address situational vulnerability in clinical research.