This study among Indian MSM revealed several common mental models regarding HIV vaccine trials, some of which indicated misunderstanding and misconceptions of procedures fundamental to clinical research. With Phase II trials planned among MSM in India in the near future, understanding potential volunteers’ perspectives on candidate HIV vaccines and vaccine trials may yield insights to support meaningful informed consent, recruitment and retention, and the safe and ethical conduct of these trials.
A major concern emerged in relation to VISP, which was perceived as a deterrent to otherwise willing MSM volunteers participating in trials. The mental model that an HIV-positive test result is the same as HIV-infection, founded on familiarity with commonly used antibody-based HIV tests in India, posed difficulties in understanding that one can be HIV-positive but not HIV-infected. Vaccine-induced infection, in addition to being feared in its own right, also resulted in the anticipation of greater regret than if one had contracted HIV due to unprotected sex. This line of thinking is consistent with omission bias, a frequently observed cognitive bias in decision-making in which harms (i.e., HIV infection) due to acts of commission (i.e., trial participation) tend to result in greater regret than harms due to acts of omission (i.e., not using a condom)
Secondly, participants indicated concern about situations requiring HIV testing in that others (e.g., wives, foreign employers, healthcare providers) may not accept that they are not actually HIV infected. VISP was similarly a primary barrier to HIV vaccine trial participation among MSM who screened in as eligible but declined to participate in a Phase IIb trial in North America; however, the main concerns were about social consequences of VISP rather than conflation of VISP with actual infection
. Concerns about VISP may be exacerbated among MSM in India due to pervasive sexual stigma and related presumptions that all MSM are living with HIV (e.g., symbolic stigma)
Participants also suggested strategies to impart understanding of VISP based on an alternate mental model derived from false-positive HIV tests, a concept with which many MSM are familiar (see Figure
1). This suggests that the pre-existing web of knowledge that may fuel misunderstanding may be marshalled to correct misperceptions about a particular concept (such as VISP), accurate understanding of which in turn may influence trial participation. Importantly, this also suggests that possible strategies to engage with mental models in order to correct misperceptions may emerge from communities themselves.
Although fear of vaccine-induced infection has been documented in studies of individuals who screened in but declined to participate in an HIV vaccine trial
 and most-at-risk populations for HIV infection
, it did not emerge as a major issue in focus group discussions. A few participants indicated apprehensions that live virus might emerge from inactivated virus vaccines and infect people. Rather, participants’ concerns were primarily focused on how to detect actual infection in a trial volunteer whose HIV-positive antibody test result might be mistaken as VISP. These concerns may be addressed by trialists through educational interventions for potential trial volunteers and by ensuring free access to viral nucleic acid-based diagnostic tests, such as polymerase chain reaction (PCR) tests
Of particular concern, preventive misconception was widely in evidence among study participants, supported by a mental model of prevention trials as synonymous with preventive interventions (Figure
2). Some participants reasoned that MSM advocates from CBOs wouldn’t refer them to a trial if there weren’t some personal benefit for participants. Participants reported that as a result, MSM trial volunteers would exhibit behavioural disinhibition through less consistent use of condoms. We identified overestimation of the likelihood of a candidate vaccine being effective in offering personal protection—a belief in the efficacy of candidate vaccines—based on a mental model of vaccines as 100% effective as well as overestimation of assignment to the experimental group. Several different rationales were revealed in support of these beliefs: 1) Vaccines, in general, were believed to provide complete protection against infection; therefore, candidate HIV vaccines were seen as likely to protect trial volunteers from HIV infection; 2) Participants reasoned that trialists would not be spending time and resources on testing a product that is not very likely to be effective; 3) Some participants articulated that trusted CBOs, with longstanding records of providing referrals to competent health and social services, would not refer clients to participate in clinical trials if the products to be tested were not going to be effective; and, 4) The view that “something is better than nothing”; so by merely participating in the trial, one is necessarily safer than in not participating.
Participants also demonstrated widespread lack of understanding of “placebo” as well as the rationale for a control group; once these concepts were explained by the interviewer, several participants and key informants still indicated overestimation of the likelihood of being assigned to the experimental group, which supported preventive misconception. Thus, mental models of prevention trials as interventions and vaccines as completely efficacious, along with lack of understanding of placebo and random assignment, were reported as likely to lead to widespread behavioural disinhibition among MSM trial volunteers.
Preventive misconception constitutes what may be an inappropriate motivation for participating in a clinical trial based on lack of comprehension of the trial’s purpose or a sense of invincibility
[44, 46, 47]. Importantly, this misconception may enable behavioural disinhibition, resulting in increased risk to participants
[37, 47, 48]. The mental model of preventive misconception (Figure
2) suggests that intervention strategies to challenge misconceptions about experimental vaccine efficacy and randomization, and thereby to mitigate the potential for increased risk behaviours (e.g., not using a condom) based on those beliefs, should include provision of explicit and consistently reinforced information and education to the effect that: 1) clinical trials are not the same as interventions; 2) most products tested in clinical trials do not work; and, 3) trial volunteers have equal chances of getting the test vaccine or the placebo.
The particular sociocultural context of kothis in India also may impact on behavioural disinhibition: the perceived opportunity to forego condom use may be experienced as consonant with kothis’ feminine gender expression and desire to attract panthis, in addition to being incentivized by saving on the cost of condoms and averting logistical challenges of negotiating condom use. Interestingly, participants invoked a former Indian AIDS education media campaign—which used a macho character to challenge the notion that one avoids HIV by being “lucky” rather than by using condoms—as a possible model for mitigating preventive misconception. The specific beliefs that contribute to preventive misconception could be integrated into such a campaign as targets for change.
Another mental model that emerged across participants was the belief that it is wrong to conceal something that might harm someone, with a strong value placed on transparency. This led to criticisms of the very basis for randomised controlled trials (RCTs), in the use of placebo-controls and double-blinding, and further influenced opinions on the importance of providing information about the outcomes of the STEP study to all potential HIV vaccine trial volunteers.
An additional permutation on the theme of transparency was invoked by key informants, who suspected that the reason for implementation of HIV vaccine trials in India is that foreign institutions want to benefit by using low socioeconomic, marginalised Indian populations as ‘guinea pigs’. In fact, conducting clinical trials in India requires technical and ethical clearance from the government, with approval by the Indian Council of Medical Research (ICMR). However, the perception among key informants, who had higher education and occupied leadership roles, that vulnerable Indian people were being used as guinea pigs may be founded on injustices and economic motivations reminiscent of the colonial era and perceived Indian governmental indifference to marginalised communities
. The disenfranchisement of MSM from mainstream Indian society may make issues of mistrust more salient in their mental models of HIV vaccine trials.
Mistrust regarding clinical trials raises the importance of explicitly addressing doubts in the minds of both MSM community leaders and grassroots level MSM about the motivations behind HIV vaccine trials and who is sponsoring the trial, along with demonstrating how the trial may benefit Indian MSM and other marginalised communities. Distrust of foreign sponsors, in particular, supports the value of having policies and funding mechanisms in place to enable access in low- and middle-income countries, particularly among trial volunteers, to HIV vaccines that demonstrate efficacy in clinical trials, once approved and licensed
Further challenges remain in how to inculcate research literacy, including basic comprehension of concepts such as placebo, randomization and the scientific rationale for RCTs, as well as how to share information about possible risks due to unpredictable negative consequences (like those in the STEP study) without unnecessarily scaring potential participants. A strategy informed by mental models might use the analogy of side effects of licensed medications, for example, to help explain unpredictable adverse effects of experimental vaccines. In the Indian context, building on a commonly used expression in Tamil, which can be translated as “effective medicine will taste bitter”, also might help to communicate risks of potential side effects to low socioeconomic status MSM.
Key informants largely corroborated the perspectives of focus group participants drawn from the clientele of MSM CBOs, including concerns about VISP, preventive misconception and difficulty in understanding the need for random assignment and placebo. Notably, ideas for possible solutions for resolving misunderstandings (e.g., in relation to VISP) emerged from both key informants and MSM clients. Different perspectives were revealed in key informants being more likely to insist on the importance of disclosing and explaining the STEP study outcomes to future trial volunteers—a position aligned with the ethical basis of informed consent
—and more likely to question the motivations of outsiders (e.g., multinational corporations and foreign governments) in conducting trials among Indian MSM.
As a qualitative study using purposive sampling, our findings may not apply across MSM populations in India; our intention was to understand in-depth rather than to generalise. In particular, the study sample may be more representative of lower socioeconomic MSM with kothi, panthi and double-decker identities who use CBO services; middle- and upper-class MSM, particularly those who have gay or bisexual identities, and MSM who do not access CBO services, may have different mental models of concepts related to HIV vaccines and clinical trials. Further research also may help to determine potential differences in mental models of HIV vaccines and clinical trials across different subgroups of MSM. An additional limitation is that participant responses may differ in response to an actual HIV vaccine trial; however our purpose was to anticipate challenges to comprehension and potential risks in advance of trial implementation.
Implications for practice and research
The evidence of broadly shared mental models related to HIV vaccines and clinical trials suggests a mental models approach may be used to support and augment efforts to inculcate scientific literacy in order to promote the ethical conduct of future HIV vaccine trials in India. Mental models may be used to impart new information that is integrated with pre-existing knowledge, as in the case of explaining VISP based on comprehension of false-positive HIV tests. Accurate assessment of the bases for potential ethical challenges in clinical research is important to effectively mitigate risks and to support meaningful informed consent
Nevertheless, mental models should be mobilised with reasonable caution, as indicated by a case study from South Africa: well-meaning foreign researchers may have mistakenly promoted folk beliefs among local communities about witchcraft as the source of HIV, thereby fuelling HIV stigma and even violence, in using what appeared to be an apt analogy of a snake to explain how antiretroviral medications work
. However, the conclusion offered in the case study that suggests one must choose either to inculcate scientific literacy or to adopt a mental models approach appears to be oversimplified. The present study suggests that efforts to promote scientific literacy alone may not be sufficient to confer understanding and acceptance of the rationale for placebos, control groups and randomization in clinical trials, nor to disavow participants and local communities of preventive misconception, or to mitigate the impact of mistrust founded on a history of colonial era abuses of medical research. A mental models approach may reveal particular misconceptions and the underlying architecture of beliefs to help guide the focus and content of scientific literacy efforts and to augment those efforts in order to improve comprehension and acceptance of the legitimacy of scientific concepts.
Importantly, the basis for preventive misconception in the present study seems to be broader than that indicated in previous empirical research conducted in the U.S.
. In addition to overestimating the likely personal effectiveness of an experimental vaccine and overestimating one’s chances of assignment to the experimental arm, we identified pervasive misunderstanding and lack of acceptance of placebo and random assignment, imputations that trialists and CBO referral sources alike must think the product will work as otherwise they would not be expending considerable resources and encouraging potential participants to volunteer, and a general belief that HIV prevention trials are intervention programs.
The present study suggests that engaging in discussion of the potential benefits and risks of clinical trials from the perspectives and belief systems of local communities, supporting policies and funding mechanisms that ensure access among trial volunteers to products that demonstrate efficacy in trials, as well as inculcating scientific literacy may help to advance the highest ethical standards in conducting research among MSM in India. Possible sociocultural differences in belief systems and the bases for trial misconceptions by population and geography suggest the importance of conducting formative research in situ before launching clinical trials, and the usefulness of a mental models approach.
Finally, although present-day trials in India are subject to government approval and ethical and safety standards, the present data suggest the importance of engaging with mental models of medical research that may be based on colonialist histories with clinical trial participants seen as “guinea pigs” or “experimental rats”, rather than merely attempting to controvert these beliefs through science. Interestingly these beliefs tended to arise more among the most educated among the sample, some of whom are advocates and service providers who viewed themselves as protecting marginalised communities, rather than among MSM clients themselves. Nevertheless, these key informants may be a highly important constituency to ensure effective community engagement through civil society representatives, which may be a key element in the successful implementation of biomedical HIV prevention trials