We largely agree with Grimwade et al ’s1 conclusion that challenge trial participants may ethically be paid, including for risk. Here, we add further arguments, clarify some points from the perspective of economics and indicate areas where economists can support the development of a framework for ethically justifiable payment. Our arguments apply to carefully constructed and monitored controlled human infection model trials that have been appropriately reviewed and approved. Participants in medical studies perform a service. Outside the domain of research (...) participation, there is nearly universal agreement that workers providing a service should be compensated fairly, and that work involving more discomfort and risk should be compensated more generously. Accordingly, labour regulations impose floors, not caps on compensation. Caps, even if intended to protect against undue inducement, also raise concerns about illegal price-fixing that disadvantages workers. Such limits on payment for egg donors have successfully been challenged in court.i Moreover, caps on compensation may harm everyone at risk of infection, not just potential participants. Insufficient compensation may impede the recruitment of enough suitable subjects, for example, when representativeness of the subject sample is required. Delays in vaccine development not only prolong disruption of social, educational and economic activity but also lead to excess infections and deaths. Unlike paid CHIM participants, individuals exposed to such infection do not accept it voluntarily, are not compensated for it, and are unlikely to receive the level of medical supervision afforded to closely monitored CHIM participants. Payment caps can lead to attempts to circumvent the regulation. For example, many countries …. (shrink)

Controlled Human Infection Model (CHIM) research involves the infection of otherwise healthy participants with disease often for the sake of vaccine development. The COVID-19 pandemic has emphasised the urgency of enhancing CHIM research capability and the importance of having clear ethical guidance for their conduct. The payment of CHIM participants is a controversial issue involving stakeholders across ethics, medicine and policymaking with allegations circulating suggesting exploitation, coercion and other violations of ethical principles. There are multiple approaches to payment: reimbursement, wage (...) payment and unlimited payment. We introduce a new Payment for Risk Model, which involves paying for time, pain and inconvenience and for risk associated with participation. We give philosophical arguments based on utility, fairness and avoidance of exploitation to support this. We also examine a cross-section of the UK public and CHIM experts. We found that CHIM participants are currently paid variable amounts. A representative sample of the UK public believes CHIM participants should be paid approximately triple the UK minimum wage and should be paid for the risk they endure throughout participation. CHIM experts believe CHIM participants should be paid more than double the UK minimum wage but are divided on the payment for risk. The Payment for Risk Model allows risk and pain to be accounted for in payment and could be used to determine ethically justifiable payment for CHIM participants.Although many research guidelines warn against paying large amounts or paying for risk, our empirical findings provide empirical support to the growing number of ethical arguments challenging this status quo. We close by suggesting two ways (value of statistical life or consistency with risk in other employment) by which payment for risk could be calculated. (shrink)

Significant attention has been given both to the ethics of Controlled Human Infection Model research and the ethics of payment for research participation. However, comparatively little attention has been given to the ethics of paying for participation specifically in CHIM research. Grimwade et al should be commended for thoughtfully addressing this topic and especially for the empirical data collection informing their work, which is too often lacking in discussions of payment for research participation. In what follows I will discuss three (...) relatively subtle factors that, I believe, make a difference to the ethical analysis of paying for research participation and raise what I intend to be constructive questions about the extent to which the survey instrument employed by the authors captures them. The authors focus on payment for risk in CHIM research. They correctly stress that compensating participants for risk is controversial and that “many general guidelines warn against paying for the risk in medical research”. While not all guidance documents share this scepticism,1 compensating for risk raises thorny issues and uncertainty over the topic among IRBs and regulatory bodies is likely to hinder the practice. Part of the difficulty in assessing payment for research risks stems from the way in which subtle variances in background assumptions influence the ethical assessment, which also complicates empirical attempts to measure attitudes on the topic. Most importantly, it is crucial to be precise about background assumptions concerning whether participants are protected from bearing the financial burdens of research risks that eventuate in actual harms. Protective mechanisms …. (shrink)

Grimwade et al highlight the current lack of a universal, standardised approach to the payment of participants taking part in controlled human infection model studies.1 As they discuss, payment for these studies is controversial, with many voicing arguments for and against higher payments, particularly for those studies which involve significant burdens to the participant. The main concerns about overpayment relate to the concepts of undue inducement or coercion, whereas underpayment raises concern about exploitation and unfair treatment. In many healthy volunteer (...) trials compensation for travel, time and inconvenience are generally accepted as fair payment, but payment for risk is less accepted, with a belief that non-therapeutic studies should only incur minimal risks, so payment for risk should not be necessary.2 This paper argues that payment for risk should be included for CHIM studies. Their findings among members of the UK public and CHIM experts from a variety of centres suggest that there is support for greater risks being associated with higher payments for participants. The amount of compensation offered by a trial has to be approved by an ethics committee/institutional review board, and some research suggests that IRB members have concerns about higher payments being offered, with only approximately one-third agreeing that payment should be offered for risk.3 Without agreement and clear guidance for calculating compensation for these types of trial, there is bound to be …. (shrink)

When payment is offered for controlled human infection model research, ethical concerns may be heightened due to unfamiliarity with this study design as well as perceptions—and misperceptions—regarding risk. Against this backdrop, we commend Grimwade et al 1 for their careful handling of the relevant issues, coupling empirical and conceptual approaches. We agree with foundational elements of the authors’ analysis, including the acceptability of payment for research risk.1 However, in our view, it is preferable to treat payment for risk as a (...) discretionary incentive to achieve adequate recruitment and retention, rather than compensation owed as a matter of fairness. Grimwade et al 1 note that although their ‘Payment for Risk Model’ was ‘created specifically in the context of CHIM research, it has the potential to inform payment in other areas of medical research.’ We agree and would go further: we do not need a special payment framework for CHIMs because there is nothing so novel about them compared with other types of research as to demand a distinct approach. Any successful payment framework must address the following ethical issues: preserving informed consent ; treating participants fairly ; encouraging adequate recruitment and retention; avoiding deception by participants; and preserving public trust.2 Some of these issues may have particular salience in the context of CHIMs, but this study design does not demand consideration of entirely distinct ethical factors when evaluating offers of payment.2 We also agree with Grimwade et al 1 about several other key points.2 Given the burdens involved and …. (shrink)

Human infection challenge studies provide illuminating case studies for several ongoing debates in research ethics, including those related to research risks and payment of participants. Grimwade et al 1 add to previous public engagement, qualitative evidence and philosophical literature on these topics.1–8 The authors advocate revision of research payment policy and practice based on their main finding that members of the public endorse ex ante payment of participants proportional to research-related risk exposure, in addition to post hoc compensation for any (...) lasting harms that occur.1 Although ‘payment for risk’ would diverge from most current research ethics guidelines, it is noteworthy that the difference in payment to participants that their framework would allow might only be small, at least in the case of currently accepted studies. The absolute difference would likely be small because the risk of currently accepted HCS participation is usually very low.9 10 On a ‘value of statistical life’ approach, mirroring actuarial accounting for fatal risks, a 1 in 100 000 risk of death might attract an extra payment of only US$96.1 Most HCS do not involve fatality risks this high, although, on pessimistic estimates, the risk of COVID-19 HCS in young healthy adults might involve similar levels of risk.11 Such risks might arguably be justified by large expected public health benefits,12,9 11 13 but it remains controversial whether higher levels of payment could …. (shrink)