Communication challenges and trial-related misconceptions.

Trial literacy emerged in all settings as a crucial component of community stakeholder engagement. Respondents across settings articulated ongoing challenges and complexities in communicating important scientific concepts to community stakeholders. Challenges were attributed in part to completely different vernacular vocabularies across multiple languages (even within country), low educational attainment among many key populations, belief in traditional healers, and lack of experience with research.

A Thai community advocate described a major component of this theme, indicating activities that promote trial literacy, such as clarifying key scientific terms and concepts, as incumbent on trial teams, and an essential precursor to invitations to participate: “At least tell us what it is, a vaccine, and then we can participate effectively, and be willing to support the trial. They must be willing to educate drug users to participate to know about the trial so they can make a decision” (PWID, KI, Thailand). A service provider from Canada articulated the importance of communication that acknowledges that various communities “have their own subculture” and the need to “speak the dialect of the population,” but described challenges in communicating about complex scientific issues: “We can talk about saturated fats and unsaturated fats; people can understand that. But the language for communicating about a vaccine is not in most people’s vocabulary” (African/Caribbean, KI, Canada). Service providers in India described lack of lay terminology to communicate “placebo” in Tamil. Peer educators resorted to analogies like “sugar water”, often failing to convey the scientific rationales behind placebo controls and double-blinding. Consequently, placebo was intuited by the local community as “deception” and “cheating”. An Indian KI explained that offering a placebo would be a deterrent to participation: “The community will not accept if we tell like this; even people who accepted [the invitation to participate] earlier will not accept, because they would be afraid that they are being cheated…they would not understand” (MSM community leader, KI, India).

Respondents across settings described challenges in encountering multiple misconceptions about key trial components. A common belief was that vaccines work by injecting a small dose of live virus: “they just put a teeny, teeny bit in your body….” (Aboriginal community, FG, Canada). A KI from Canada suggested this perception was common in their community: “There’s a lot of misconceptions about what a vaccine actually is; people will think, ‘Oh my god, you want to poke me with HIV to make me immune; you’re f—ing nuts’” (PWID, KI, Canada). A stakeholder from India similarly questioned the reliability of a vaccine containing deactivated virus: “You said dead virus is put in. How do we know…after going in it drinks blood and becomes alive?” (Kothi/MSM, FG, India).

Common misunderstandings about vaccines influenced conceptualizations of VISP, the indication, sometimes time-limited, of seropositivity as a normal immune response to HIV vaccination [49]. Across settings, community stakeholders expressed dismay about possible VISP, suggesting that if they tried to explain it to local communities it would deter trial participation: “They will get real scared and confused and run away” (MSM peer educator, KI, India); “Try to explain this to somebody who speaks Cree or Ojibwa, and there aren’t words to describe this” (Aboriginal peer educator, FG, Canada). A transgender peer educator from Thailand explained, “When I first heard that my blood would become positive after I’m vaccinated, I wondered if my body would be able to prevent HIV” (TG, KI, Thailand).

Community members were seen as trying to make sense of complex scientific information about vaccines and clinical trials by drawing on existing knowledge or experience. A Thailand KI described challenges in communicating about a vaccine trial in that “people still have old beliefs…some communities have heard about herbal medication for HIV that costs only 800 Thai baht [~$25 USD]; if it doesn’t work, they will get lifetime healthcare for free. So we need to explain to them that our vaccine is not like that….” (Clinical trialist, KI, Thailand). A South Africa KI explained: “People take the little snippet of information they’re given and they wrap it into their local belief systems…and from there try to make sense of it. And it’s not surprising that there are just incredible amounts of misunderstanding how it works” (CSO rep., KI, South Africa). Thus, KIs and FG participants reported a broad range of trial-related misconceptions and communication gaps about key vaccine, clinical trial- and HIV-related concepts, and highlighted difficulties that emerge in trial literacy activities.

Preventive misconception.

Misunderstandings about the nature of clinical trials, placebo-controls, randomization, and conflation of HIV prevention trials with prevention programs were identified, in particular, as supporting preventive misconception and risks for behavioral disinhibition. Preventive misconception (analogous to “therapeutic misconception”, i.e., “failure to appreciate the difference between research and treatment” in clinical trials [50]) is the tendency for participants in prophylactic clinical trials to overestimate the probability of being assigned to the experimental versus control group and/or to assume that the experimental drug or vaccine being tested is effective [37,51].

Some respondents feared their communities would perceive a trial vaccine to confer 100% protection. As a Canadian KI explained, “The understanding of vaccine to the general public means I am immune: you have given me the invisible cloak; you’ve given me the Superman suit. I’m all good” (African/Caribbean, KI, Canada). A KI from India explained, “[Trial participants] may not know much information about placebo. They will believe that ‘I have been given an HIV vaccine, I can do whatever I want” (MSM peer educator, KI, India). Frequent confusion was evinced across settings with community stakeholders alternating between talking about “vaccine” and “cure,” “trial” and “program,” demonstrating conflation of HIV prevention and treatment trials, and of trials and interventions. A Thailand KI reported in reference to an HIV vaccine trial, “Some people get confused that this vaccine works as a cure,” and further, that “something new that they find out about comes in the form of hope, too” (Service provider, KI, Thailand). An India KI reasoned that researchers wouldn’t invest time and money in testing a candidate vaccine unless they already knew it worked: “If it is not working, then why would they be actually testing it?,” (MSM peer educator, KI, India) reflecting a significant disjoint in understanding between researchers and community stakeholders indicative of preventive misconception.

Histories of colonialism and exploitation.

Conceptualizations of clinical trials and biomedicine were described in the context of historical experiences with colonialism, marginalization, and exploitation in each of the case settings. In Canada, an Aboriginal community stakeholder revealed not lack of understanding but historically-based mistrust as a primary challenge to stakeholder engagement: “Our people don’t trust the government anymore because we’ve been cheated so many times. The Whites brought polio to our people, other diseases. It’s the government telling us, ‘take it, it will not hurt you’” (Aboriginal peer educator, FG, Canada). Analogously, in South Africa a community stakeholder voiced concerns rooted in the historical oppression and exploitation of Africans: “You have people who have the perceptions that these trials are not meeting ethical standards, that people are being harmed, people’s rights are not being adequately respected—the notion that these trials are happening in Africa and Africans are being used as guinea pigs” (CSO rep., KI, South Africa). In both India and Thailand, concerns emerged around why trials needed to be conducted in their countries, if safety protocols were being followed, and if testing was also being conducted in rich countries. An India KI reported, “I even doubt whether a Phase I trial [in India] among normal human volunteers was actually conducted” (Service provider, KI, India).

Community stakeholders across key populations at risk for HIV and across settings interpreted their being recruited for trials due to their high risk as unethical:

It’s almost inherent in the study that in order for them to be able to really study the effects of the vaccine, they really, in essence, want you to contract HIV and that’s why you’re chosen for the study, because you’re in a high-risk group for HIV infection. And so a small voice in my head is saying, well, this is kind of f—d up. (Former trial participant, KI, Canada)

In South Africa, certain community members reportedly viewed researchers with suspicion, a view potentially intensified by negative trial results, as “playing with participants’ lives.”

Community respondents described experiential knowledge through face-to-face communication, including testimonials from former trial participants, as crucial elements of building trust with researchers. An Indian MSM recommended, “Let them say that, ‘We also volunteered like you. We did not have any problem.’ Like that, if they give us 100% confidence, they [MSM] will come definitely” (Kothi/MSM, FG, India). An Aboriginal stakeholder reported, “I will wait to see the regular people who come in for two years to take the vaccinations; and then I’d see if any of them drop dead or grow buffalo humps…then I might…start considering it after that” (Aboriginal gay man, FG, Canada). A South African respondent articulated the need for ongoing communication as key to offsetting mistrust: “let people know how things are going, and if there is a problem, be honest” (CSO rep., KI, South Africa).

Global disparities in resources.

Disparities between trialists/sponsors and trial sites emerged as a significant element of mistrust, with a common construal of low-income country participants being used as “guinea pigs” to benefit high-income countries. An Indian service provider asserted that Indians were being used as “guinea pigs” and transposed concerns rooted in colonialism to present day economic disparities: “Most of these trials are deliberately conducted among people who are economically disadvantaged and who are from developing countries” (Service provider, KI, India). A South Africa CSO representative described community-based concerns that “Africans are being used as guinea pigs.” A Thailand community advocate wanted evidence of trials abroad before local implementation: “We would watch and see someone else first, especially…if people in Washington or New York are being vaccinated or not. If they are…not just the black people or others, then…if it is the nice looking university students, then, OK…probably OK” (CSO sex worker, KI, Thailand). An India community leader was similarly curious about “whether trials are happening in other countries?…Why does this need to be conducted among MSM in India…?” (MSM, KI, India).

Early trial cessations.

Respondents in Canada and South Africa, sites of the Step Study and Phambili trials, respectively, in which vaccinations and enrollment were suspended due to unforeseen risks to some vaccine recipients [26,27], indicated associations between trust and how early trial cessations are managed. A Canadian community advocate explained how past history can be connected with current experiences of trial closures: “They [PWID] hate them [medical providers]; they feel persecuted by them; they feel belittled and judged, and I don’t blame them because they are…. There has to be some repair done. I think they’ve widened the gap of mistrust. I might feel like I was lied to” (PWID, KI, Canada). A former trial participant expressed concern in how he had received information about the trial cessation and possible increased susceptibility:

The way I found out about this was through the media so initially there was some hostility on my part because I felt well, I’m in this study, if I’m finding out through the media that means that someone knew a week ago at least, you know what I mean? It’s very scary when you find out about something that you’re involved in, not from the people that you were working with but from an outside source. (Former trial participant, KI, Canada)

A South African researcher highlighted the need for trialists to clearly explain the chance of early trial termination, stating “People get really psyched up and invested in a trial”, while also admitting, “I don’t think we communicate that possibility as well as we need to” (Researcher, KI, South Africa). A former participant’s experience embodied this researcher’s concern, further revealing mistrust: “They never actually said that anything like this could possibly happen, but of course if they did nobody would take the trial” (Former trial participant, KI, Canada).

Early engagement.

Respondents across case studies highlighted the importance of engaging community stakeholders early in trial planning processes. A South African CSO representative stated, “An ideal model of community engagement would involve communities during protocol formulation stages to determine the community’s perceptions of the social value of the research.” Early engagement was articulated as an important avenue to work through historically-based mistrust, a mechanism through which community stakeholders would feel a greater sense of control and ownership in contributing to the research endeavor. Respondents across settings endorsed early involvement as a key component of achieving meaningful engagement.

Communities need to be engaged more over the life of a trial: They should not only be engaged during community meetings when trials are recruiting and then again when results are going to be announced: this does not constitute meaningful community involvement. (CBO rep., KI, South Africa)

Community stakeholders from Canada, while indicating the importance of early engagement, expressed caution as to how it is implemented. An Aboriginal peer educator advised the importance of engaging informal leaders and community Elders, but articulated challenges in knowing who to approach: “And it seems like decisions are getting made in the Chief Council, but it’s some little old lady cooking soup in the back of the center who actually everyone checks in with first”; and further that “outsiders”, including HIV experts and leaders, should go through Aboriginal political leaders rather than approach Elders directly: “You can’t really say, ‘I’m 30-years old; okay, Elders, come get educated by me’; I mean, that’s not respectful” (Aboriginal community, FG, Canada).

The breadth of “community” representation.

A challenge to community stakeholder engagement was expressed in terms of overly narrow conceptualizations of who constitutes local community. A Canadian community stakeholder stressed, “the whole community, everyone should be involved”, including different ethnic/racial and socioeconomic backgrounds: “That way it’s being tested so that all populations can say this is something that is correct data” (Female sex worker, KI, Canada). Yet community stakeholders described that recruitment and consultation across a broad spectrum of community members is limited. An Indian stakeholder lamented that consultative processes were limited to individuals with existing CBO linkages: “Since I am working in a CBO, [trialists] invited me [for a consultation meeting]; others thus do not know about this and could not participate” (MSM community rep., KI, India). A South Africa CSO representative expressed concerns with “site hand-picking” of community members (CSO rep., KI, South Africa). In particular, a South Africa KI explained that community advocates are often distanced from trial involvement, approached as an afterthought, and constrained to narrowly proscribed roles: “Advocates are seen as the necessary noise that should come after the agenda has been drawn, instead of being the ones drawing some of the agenda because they are so much in touch with communities” (CBO rep., KI, South Africa).

Clear and appropriate roles.

CSO representatives articulated the importance of tailoring roles and responsibilities to people’s skills, capacities and preferences, and challenges and uneven implementation of this recommendation. A community member felt that involvement should be comprehensive, saying “My community wants to feel empowered; they want to feel engaged. Engage them in the actual setting up of the trial, in recruiting for the trial. Include them in every aspect” (PWID, KI, Canada). Yet a South Africa CSO representative explained that involving everyone in every step of the planning process would not necessarily lead to positive outcomes: “If you have people at the table not because they are going to contribute in work but because they just want to be there, then you are going to expand the amount of work that needs to get done and the complexity of it, but not necessarily improve the outcome” (CSO rep., KI, South Africa).

CSO and other stakeholders articulated specific roles for advocacy organizations and community advisory boards (CABs) that drew on their existing strengths. Several KIs explained that advocates play a particularly important role in explaining scientific results to community stakeholders and acting as a bridge to biomedical stakeholders, even more so when a trial is terminated early:

So, when things get difficult and you need friends; or you have a hard time like when a trial closes early; you already have people who have a relationship with you, who are aware of your intentions; can be the voice in the community and with the media and with other stakeholders to help get the message out and do some damage control. (CSO rep., KI, South Africa)

However, community advocates perceived that their effectiveness in this role was constrained by unequal power dynamics and limited communication with research teams. An Indian CBO leader expressed frustration about abrupt cessation in communication from researchers regarding a planned vaccine trial that was terminated after the Step Study cessation, explaining that long-term credibility and trust with research stakeholders was jeopardized:

No proper information was given why they were no longer calling us… A meeting that was scheduled was cancelled. I could not face my community people when I had already spread messages about the trial coming. They were asking, ‘What is happening now? You asked us to come for meetings and now no noise’. I was very angry at that time. I felt as though we were being used–like a ‘use-and-throw’ [disposable object].” (MSM CBO rep, KI, India)

This commentary also typifies the need to address unequal power dynamics between CBOs and research teams. CBO representatives sought assurances that they would be consistently supported and engaged rather than simply “used” to recruit participants.

KIs asserted that while CABs may serve key functions in bridging community and researchers, they often lack sufficient leverage and control within the research team to insist on certain priorities, particularly when they are beholden to research stakeholders for their funding. A South African KI questioned the extent to which CABs could operate autonomously from research teams: “I also think the CAB’s being constituted by the research community and being sustained by the research community introduces some bias to what they do” (CSO rep., KI, South Africa). Another South African KI highlighted the differing capacities of CABs to assert their own priorities: “I’ve seen many CABs, not all CABs, being empowered enough to engage actively in the research” (CSO rep, KI, South Africa).

The benefits of engagement.

Benefits of meaningful community stakeholder engagement were articulated by CSO representatives and advocates, who described wanting to contribute to ethical oversight of trials that contribute to their communities, and by community stakeholders, who reported feeling themselves a part of a team with a common goal in a shared research endeavor. Some former Step Study volunteers in Canada expressed positive feelings despite early trial termination: “I felt a bit like a pioneer…I was actually quite proud to be part of something that could have some far-reaching impact” (Former trial participant, KI, Canada). Another Canadian volunteer echoed these sentiments, saying they felt they were “an important part of the whole team”: “They didn’t just treat me like a patient or a research study participant. I felt like I was an important part of the whole process. I wasn’t just a guinea pig” (Former trial participant, KI, Canada). A Thailand trialist similarly described the camaraderie developed among some volunteers: “Now we are having a club in our trial for our participants who want to create some kind of HIV/AIDS campaign in the future” (Clinical trialist, KI, Thailand). CSO representatives in South Africa asserted that meaningful engagement can help to offset potential mistrust associated with negative trial results: “when a trial closes early, you already have people who have a relationship with you to help get the message out” (CSO rep., KI, South Africa).