Human Infection Studies have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid ‘undue’ levels of inducement to participate. Through this embedded ethics study, involving 97 healthy volunteers and other (...) research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers’ attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning. (shrink)

We thank the authors of the five commentaries for their careful and highly constructive consideration of our paper,1 which has enabled us to develop our proposal. Participation in research has traditionally been viewed as altruistic. Over time, payments for inconvenience and lost wages have been allowed, as have small incentives, usually in kind. The problem, particularly with controlled human infection model research or ‘challenge studies’, is that they are unpleasant and time-consuming. Researchers want to offer carrots to incentivise participation. We (...) are proposing that research participation be viewed as a job with the full suite of financial entitlements of fairly remunerated work, including payment for risk and labour law protections. This would be a significant shift from current practice and standards. Ambuehl, Ockenfels and Roth have grasped this basic point and have beautifully elaborated how a fair price could be arrived at using economic theory. They build on our proposal helpfully and suggest ‘ salary for time involvement that is adjusted to account for the amount of discomfort experienced during participation, insurance against ex post adverse outcomes and ex ante compensation for risks that cannot be compensated ex post.’3 This effectively addresses Fernandez Lynch and Largent’s2 concern that compensation for risk is inappropriate for harms which do not eventuate. However, because death cannot be compensated for, there must be payment for risk of death, as Ambuehl, Ockenfels and Roth convincingly argue.3 Indeed, the three-part model suggested by Ambuehl, Ockenfels and Roth makes us realise that job model would be a better title for our model than a payment for risk model. The alternative to a properly remunerated job model is the original altruistic model. However, this …. (shrink)

The peer commentaries on our Target Article, “Promoting Ethical Payment in Human Infection Challenge Studies,” offer a number of insights that will help advance the co...

The COVID-19 pandemic has necessitated rapid research to aid in the understanding of the disease and the development of novel therapeutics. One option is to conduct controlled human infection trials (CHITs). In this article I examine the history of deliberate human infection and CHITs and their utilization prior to the COVID-19 pandemic, key ethical considerations of CHITs in the COVID-19 setting, an analysis of the World Health Organization’s (WHO) Key criteria for the ethical acceptability of COVID-19 human challenge studies, and (...) a review of the two COVID-19 CHITs that have already commenced, their compliance with the WHO criteria and other ethical considerations. (shrink)