Stakeholder Views on the Acceptability of Human Infection Studies in Malawi

"...ongoing two-way dialogue is needed, as started through this consultation."

Often conducted as part of vaccine testing, human infection studies (HIS) raise challenging questions for ethical practice and community engagement in that they involve the deliberate infection of healthy adult volunteers with a microbial pathogen. In 2017, the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MLW) organised a workshop to reflect on the implications of planned Streptococcus pneumoniae HIS work in Malawi (the Malawi Accelerated Research in Vaccines using Experimental and Laboratory Systems (MARVELS) project). Participants identified a need for community consultation to understand the acceptability and ethics of HIS in the Malawi context. This study responds to that recommendation. One aim is to support the wider development of ethical frameworks for HIS science in Malawi and other low- and middle-income countries (LMICs).

The MLW project conceives of a series of HIS, starting by establishing the feasibility of carriage in 12-36 participants. If effective, the project would move to further stages of vaccine testing, scaling up to around 150-400 participants per study depending on the stage and study focus. Volunteers would be exposed to pneumococcus through a saline solution dropped into the nose, and closely monitored for safety.

Taking care with how they presented information about the HIS, the researchers conducted 6 deliberative focus group discussions (FGDs) with MLW frontline research staff, medical students, and 3 sets of community representatives: chiefs (local community leaders), religious leaders, and members of MLW's Community Advisory Group (CAGs). The CAGs comprise representatives of active community-based organisations located in rural or urban Blantyre. CAG members were elected by their communities, and their main role is to advise MLW on appropriate engagement with communities for research. To allow participants to reflect and share considered perspectives, the researchers conducted follow-up interviews after 2-3 weeks with 3 participants from each FGD. Finally, they conducted 5 key informant interviews with research ethics committee (REC) members, senior clinicians at the hospital where MARVELS would take place, and district health management officials.

In sharing results, first, the paper describes stakeholders' views on pneumococcal HIS, including perceived benefits, concerns, and views about whether overall pneumococcal HIS might be acceptable and ethical in Malawi. For instance, a vaccine developed specifically for the Malawi context was considered valuable given differences in genetic background and environmental context (e.g., compared to studies done in Europe). While stakeholders saw HIS as having potential benefits, they also had concerns. Key issues highlighted by all stakeholder groups were safety and community reactions. For example, participants mentioned the potential for rumours about the purpose of deliberate infection, links to witchcraft, and the intentions of non-Malawian researchers, particularly because MLW may be seen as a foreign institution. Potential community distrust of HIS was seen by all stakeholder groups as likely to limit the recruitment of HIS volunteers.

Second, the paper reports stakeholders' suggestions on the requirements for pneumococcal HIS to be acceptable, including appropriate models of consent, a fair selection of research participants, and the availability of medical support. For instance, participants emphasised that explanations of HIV should be particularly clear and open, given concerns about community misconceptions, perceived potential for risk from deliberate infection, and complexity of information. One medical student expressed uncertainty about how to balance openness and avoiding concern, given that the idea of being infected may cause fear. Many stakeholders discussed involvement of family members in consent, reflecting a concern not to harm family relationships or household livelihoods and dominant norms around permission from family members, particularly for women.

The perceived importance of informed and voluntary consent had implications for views about acceptable recruitment approaches. The MARVELS team was considering using flyers or adverts distributed through places such as college notice boards or social media, with phone numbers to contact for further information. Stakeholders welcomed this approach as avoiding pressure to take part (perhaps in contrast to the more typical of face-to-face recruitment in communities). Views on groups of who should be either preferred for participation or excluded reflected concerns related to the health status of HIS participants, informed and voluntary participation, community interest and misconceptions, equitable opportunities for participation between different population groups, burden on livelihoods or other activities, and efforts to ensure research value and validity through a sample population considered relevant and unbiased - principles that were sometimes in tension.

In addition to compensation of volunteers participating in HIS research, community engagement was considered by all stakeholders to be key component if HIS research is to be accepted in Malawi. Comments on community engagement focused on raising awareness, sharing information about HIS, and providing an opportunity for people to ask questions. A few stakeholders also mentioned more two-way engagement with community input to HIS design, particularly seeking feedback from participants once HIS research begins. Participants suggested a range of channels, including working with chiefs, community opinion leaders, and the media to reach potential participants and wider communities. Community stakeholders also recommended the presence of a HIS scientist during any community engagement activity to respond to questions and give clear information.

Third, the paper describes views on HIS for other diseases beyond pneumococcus. Reasonable compensation and clear information on the procedures were identified as preconditions for acceptability.

In discussing the findings, some suggestions emerge that may be relevant to HIS in other contexts, including:

• Inclusive forms of communication that reach all potential participants should be considered for future HIS (e.g., provide engagement material in local languages).
• There is a need for communities to perceive the study as relevant to them, not just for the results to be medically applicable; limiting inclusion was seen as potentially limiting wider community interest and support, and potentially future vaccine uptake.
• A two-way approach is core to guidance on public engagement in LMICs and is needed both to inform the acceptable design of future HIS and for the intrinsic value and ethical importance of public involvement.
• HIS should have a publicly available rationale that includes explaining why HIS is needed rather than alternatives.

Within MLW, the findings informed the decision to proceed with a pneumococcal HIS feasibility study and were used in the study design. Summarised findings were also shared with the Malawi national ethics committee to support their ethical review of the feasibility study, and with the MARVELS funder. The researchers "plan to continue embedding social science in MARVELS and future HIS in Malawi to understand participant experiences and views of people who choose not to take part, to develop our understanding of acceptability, enable ongoing adaptation of HIS study design to optimise acceptability and to inform discussions on ethical approaches to HIS in LMIC settings."