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

ABSTRACT

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens (or other micro-organisms). There have been recent calls for more HCS to be conducted in low-income and middle-income countries (LMICs), where many relevant diseases are endemic. HCS in general, and HCS in LMICs in particular, raise numerous ethical issues. This paper summarises the findings of a project that explored ethical and regulatory issues related to LMIC HCS via (i) a review of relevant literature and (ii) 45 qualitative interviews with scientists and ethicists. Among other areas of consensus, we found that there was widespread agreement that LMIC HCS can be ethically acceptable, provided that they have a sound scientific rationale, are accepted by local communities and meet usual research ethics requirements. Unresolved issues include those related to (i) acceptable approaches to trade-offs between the scientific aim to produce generalisable results and the protection of participants, (iii) the sharing of benefits with LMIC populations, (iii) the acceptable limits to risks and burdens for participants, (iv) the potential for third-party risk and whether the degree of acceptable third-party risk is different in endemic settings, (v) the conditions under which (if any) it would be appropriate to recruit children for disease-causing HCS, (v) appropriate levels of payment to participants and (vi) appropriate governance of (LMIC) HCS. This paper provides preliminary analyses of these ethical considerations in order to (i) inform scientists and policymakers involved in the planning, conduct and/or governance of LMIC HCS and (ii) highlight areas warranting future research. Insofar as this article focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided is relevant to HCS (in HICs or LMICs) involving pandemic diseases including COVID19.