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Compensating for research risk: permissible but not obligatory
  1. Holly Fernandez Lynch,
  2. Emily A Largent
  1. Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
  1. Correspondence to Professor Holly Fernandez Lynch, Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; lynchhf{at}

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When payment is offered for controlled human infection model (CHIM) 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.

Where we agree

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 (avoiding coercion and undue inducement); treating participants fairly (avoiding exploitation); 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 importance of the research, CHIM participants deserve substantial payment. Moreover, it is problematic to focus ethical attention only on high payment, especially because payment cannot coerce and concerns about undue inducement are often overblown.3 In contrast, low payment raises important concerns about exploitation and inadequate participation.3 Payment can neither fix otherwise unethical research nor render ethical research unethical; it also should not be treated as a benefit to counterbalance risk for purposes of study approval.

Where we diverge

Despite significant areas of agreement, we are not convinced by Grimwade et al’s1 argument that payment for risk must be offered as a matter of fairness.

Paying research participants can serve various functions, including compensation and incentivisation.4 In turn, these functions support the ethical goals of treating participants fairly and achieving adequate recruitment and retention, respectively, which must be balanced against the goals of preserving informed consent, avoiding deception, and promoting trust.2

Compensation for participant time, effort, and burden is essential as a matter of fairness. When these contributions are left uncompensated, participants experience a loss or deficit which they should not be expected to bear when engaged in a socially valuable endeavour like research. Therefore, even though it is possible that compensation payments may render research participation more attractive than a participant’s other opportunities to make money, the importance of fairness outweighs the possibility of undue influence or deception and can actually promote trust.2

Grimwade et al 1 also call for compensation of research risk. But uncompensated risk is not necessarily experienced as a deficit by participants. If risks fail to materialise into harm, the participant is left no worse off; if risks do materialise into harm, compensation for risk cannot substitute for compensation for the harms experienced. In our view, because research risks do not move a participant from their baseline until they become harms, compensation for risk is not owed as a matter of fairness. Accordingly, if it is offered, any concerns about undue inducement would need to be countered by something other than fairness.2 4

For example, risk-based compensation might be permissible if concerns about undue inducement are very low, which is likely for many CHIMs involving very low risk and correspondingly low risk-based compensation.1 Concerns about undue inducement might be more significant for CHIMs involving greater risk, perhaps like those contemplated for COVID-19. In this context, risk-based compensation would be higher, making it more likely that research participation will appear more attractive than alternatives, potentially leading to poor judgement. This concern could be countered by arguments focused on consistency—for instance, we accept risk-based compensation for employment. Alternatively, we might focus on arguments rooted in concern about adequate recruitment and retention, that is, that participants will be unwilling to enrol quickly enough or in adequate numbers if not paid for assuming risk. But in that case, risk-based payment is better conceptualised as an incentive than as compensation—and incentives are not owed as a matter of fairness. Rather, they are offered as needed to support the timely completion of important research. What this ultimately means is that payment for research risk can be acceptable, but should not be viewed as obligatory.2

What is obligatory, however, is compensation for research-related harm if and when it occurs, as these harms lead to true deficits for participants and their families, including medical expenses, lost wages, pain and suffering, and even death. Grimwade et al 1 articulate this position, as has every major ethical body to consider the issue5—although, the authors also hedge a bit, saying that ‘allowing for the upfront payment for risk will allow some level of protection for participants of studies that may not have adequate harm compensation available.’1 But payment for risk will often be a pittance, if calculated using analogies from non-research contexts, and insufficient in the face of substantial harm.1 The fact that compensation for harm is not guaranteed in research across the globe, most especially not in the USA, is a critical failing of the research enterprise. Remedying that failing is far more important than quibbling over whether payment for risk is obligatory or merely permissible.

Finally, we acknowledge that Grimwade et al’s empirical data from a survey of the UK public indicate high levels of agreement that participants should be paid for both risk and any harms that occur. Grimwade et al interpret these findings to suggest that ‘not only do the public believe it is ethically justified to pay for risk, but that they may even consider it a necessary condition for the fair compensation of CHIM participants.’1 We would stop short of that conclusion. It may be that survey respondents’ opinions reflect a lower willingness to participate in CHIMs if payment for risk is not provided, rather than an innate sense of what is fair. This would justify risk-based payment as an incentive to support adequate enrollment without necessarily supporting the conclusion that payment is needed as a matter of fairness. Nonetheless, these public perspectives are useful in informing how payment for CHIMs may need to be structured in order to meet the expectations of potential participants. And even if public perspectives do not necessarily dictate normative conclusions about what is fair, as an instrumental matter, satisfying perceptions of fairness may be critical.

In the end, our areas of divergence from Grimwade et al’s1 conclusions are exceedingly slim. Prevailing ethical concerns about payment are likely resulting in failure to treat participants fairly and contributing to recruitment that may be slow and inadequate. Attention currently devoted to worrying about the ethics of research payment would be better spent on promoting high-quality ethical review of research and robust informed consent.



  • Twitter @hollylynchez

  • Contributors HFL wrote the first draft. Both authors contributed to conceptual analysis, substantive editing, and final approval of the manuscript.

  • Funding This authors receive funding from the Greenwall Foundation as Faculty Scholars (no award number).

  • Competing interests Both authors received an honorarium from 1Day Sooner for producing an independent report on the ethics of payment for participation in human infection challenge studies:

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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