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 for more than minimal risk studies is 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.

Factors influencing participation in controlled human infection models: a pooled analysis from six enteric fever studies

“…Previous studies have demonstrated an inverse correlation between education and financial reward as a motivator and education, suggesting that highly educated people may be less likely to need the money or less susceptible to financial inducement 15 . As these studies were set in a high-income context the survey results may not be generalizable to low-income countries where (at present) ~7% of challenge studies are conducted 8 and the ethics of financial benefits may need a higher level of scrutiny 11 .…”

“…Identification and recruitment of willing volunteers for such studies can pose distinct challenges-in a recent study 120,000 potential recruits were contacted to recruit 112 participants 9,10 . One study on the experiences and perceptions of participants in a malaria challenge study in Kenya focussed on ethical considerations appropriate to a malaria endemic setting 11 . There is otherwise a paucity of research on factors motivating participants to enrol in human challenge studies.…”

“…There is otherwise a paucity of research on factors motivating participants to enrol in human challenge studies. In particular, it is unclear as to whether financial considerations are the main driver and whether level of education should be an important inclusion criterion when recruiting volunteers to challenge studies 11 . An improved understanding of participant experience could help optimise the design and conduct of future challenge studies.…”

Risk assessment for the implementation of controlled human Schistosoma mansoni infection trials in Uganda

“…Alternatively, volunteers may be displaced to a non-endemic region for the study duration. However, the prolonged, seven to 12-week "admission" required for the CHI-S would be a major burden and inconvenience, as opposed to the relatively short-duration (24 days) for malaria CHI studies where such approach has been employed 14 . The possibility of volunteers absconding during the study, given the long duration, might be significant, abrogating the value of such an approach.…”

Exploring willingness to participate in future Human Infection Studies in Lusaka, Zambia: A nested qualitative exploratory study

“…HIS can accelerate vaccine development by facilitating an understanding of pathophysiology and mechanics of immune response under highly controlled conditions and to efficiently test vaccine or drug efficacy. The intentional infection of healthy study participants with a viable challenge agent or pathogen under highly controlled conditions [6], could potentially raise public concerns, queries, and ethical complexities particular to LMIC settings; including concerns around communal pressure to participate, local language wording in information sheets, beliefs on blood collection, adequacy of infection control measures in the community, and appropriateness of compensation given levels of poverty [7]. Additionally, the daily risk posed in some LMIC environments makes it difficult to control HIS participants' exposure to additional diseases or the spread of infection into the larger community without residency requirements [7].…”