Ethical considerations in Controlled Human Malaria Infection studies in low resource settings: Experiences and perceptions of study participants in a malaria Challenge study in Kenya

Abstract

Background:The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) studies, in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities and increasing capacity development initiatives. However, the ethical issues these studies present in LMICs have not been empirically studied. We present findings of a descriptive social science study nested within a malaria volunteer infection study, on-going at the time of writing, at the KEMRI-Wellcome Trust Research Programme (KWTRP) on the Kenyan Coast.Methods:The study included non-participant observations, five group discussions with more than half of the CHMI study participants, two in-depth interviews with study team members, and an exit questionnaire administered to the participants.Results:Participants understood the key elements of the study, including that they would be deliberately infected with malaria parasites and may get malaria as a result, there would be regular blood draws, and they would spend up to 24 days in a residence facility away from their homes. The greatest motivation for participation was the monetary compensation of 20 USD per overnight stay given as a lump-sum at the end of their residency stay. Also appreciated were the health screening tests prior to enrolment and the positive relations with the study team. Concerns raised included the amount and regularity of blood draws experienced, and concerns that this type of research may feed into on-going rumours about research generally.Conclusion:With the increasing range and number of CHMI studies being conducted in LMICs, current ethical guidance are inadequate. This study highlights some of the ethical issues that could emerge in these settings, emphasizing the heavy responsibility placed on research review and regulatory systems, researchers and funders, as well as the importance of carefully tailored community engagement and consent processes.

Stakeholder views on the acceptability of human infection studies in Malawi

“…Some stakeholders felt HIS volunteers should receive higher amounts, in line with suggestions in some guidance [34]. However, other stakeholders were concerned about undue influence, a concern widely shared in literature [2,13,28] and of particular significance in LMIC contexts where poverty may increase the value of study compensation [10]. Existing research in Kenya shows compensation can be a key driver of participation [10], but other studies in Kenya suggest compensation did not involve undue influence, and also did not set a precedentanother concern for some stakeholders in Malawi [8].…”

“…However, other stakeholders were concerned about undue influence, a concern widely shared in literature [2,13,28] and of particular significance in LMIC contexts where poverty may increase the value of study compensation [10]. Existing research in Kenya shows compensation can be a key driver of participation [10], but other studies in Kenya suggest compensation did not involve undue influence, and also did not set a precedentanother concern for some stakeholders in Malawi [8]. While many stakeholders suggested amounts for financial remuneration, some talked about access to health care as a potential form of compensation, reflecting the costs of accessing high quality (private sector) health care in Malawi.…”

“…Challenges are particularly apparent in LMICs. For example, informed consent and fair compensation are complex in contexts of limited research experience and high poverty; health systems may lack adequate facilities to monitor and treat adverse events, and regulatory guidelines may be limited [2,4,[8][9][10]. The growing literature on HIS ethics suggests a range of ethical principles, including a strongly justified research question that can only be answered through HIS, independent review, qualified and experienced researchers, rigorous informed consent, safe selection of participants, minimisation of risks and no irreversible harm, protection of contacts and the environment, compensation that avoids undue influence, compensation for harm, and public involvement [4,6,8].…”

“…The growing literature on HIS ethics suggests a range of ethical principles, including a strongly justified research question that can only be answered through HIS, independent review, qualified and experienced researchers, rigorous informed consent, safe selection of participants, minimisation of risks and no irreversible harm, protection of contacts and the environment, compensation that avoids undue influence, compensation for harm, and public involvement [4,6,8]. However, further evidence is needed to guide researchers and ethics committees on appropriate frameworks for HIS, particularly in LMICs [10,11].…”

Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy

“…Recent social science work with participants has suggested that HCS participation, particularly in inpatient studies, can lead to a wide range of burdens. 49 Certain study interventions will be more burdensome for some individuals/populations than for others. Due to cultural beliefs regarding the value/importance of blood, for example, blood draws (especially of larger volumes) may be especially worrisome, and thus burdensome, to some research participants in sub-Saharan Africa.…”