HCV CHIM Community Advisory Committee

The following document, adopted on November 27, 2023, represents the opinion of the HCV CHIM Community Advisory Committee, derived independently of researchers responsible for implementing the proposed HCV CHIM. 

We are enthusiastic about the prospect of a controlled human infection model (CHIM) to facilitate the future testing of much-needed vaccines for hepatitis C. We believe that with proper care and oversight, hepatitis C CHIM studies can be done ethically and to great scientific benefit.

No study can take place without dedicated volunteers. Accordingly, compensation of volunteers must be carefully considered as a matter of ethics, fairness, and justice. This Committee believes that in determining compensation for volunteers in any future HCV CHIM, the burdens and discomforts imposed upon participants, the high potential social value of the proposed studies, and wider considerations of economic justice must be given very substantial weight.¹ Payment should not necessarily be pegged to market wages for “unskilled labor”.² While very different in character, the “labor” of participants in this case is significantly more valuable for society, and moreover, market wages for unskilled workers are not necessarily just for unskilled workers themselves, making it an inappropriate benchmark.

In light of these factors, we have previously stated that an HCV CHIM study should aim for compensation between US$15,000 to US$20,000 for those infected for six months before treatment initiation as a baseline. This figure is high by the standards of many clinical trials, but appropriate considering the related burden, social value, and risks involved. Ultimately, ethicists, regulators, and researchers must do their utmost to ensure they are not underpaying participants, because this would be unfairly exploitative.³

While logistical and budgetary concerns may necessitate payments below our preferred range, we reject the notion that $20,000 would be so high as to endanger prospective participants, especially low-income participants, by exposing them to undue inducement. 

Compensation limits merely push the supposed problem of undue inducement down the socioeconomic ladder: while a few thousand dollars may not be unduly “tempting” to those of higher socioeconomic status, it still may represent a profound amount of money for someone less well off. In other words, no matter how low you go, there will always be someone somewhere who is extremely financially needy. A payment cap simply leaves them worse off. Thus, payment limits simply concentrate burdensome, riskier research on the economically disadvantaged.⁴ It follows that higher payments could aid in equitable research recruitment.⁵

Focus on payment may distract from underlying issues of informed consent. The informed consent process must guard against anyone joining a clinical trial without due consideration and understanding of the risks involved; if the concern is that money may be too tempting, a study should either pay nothing or address the underlying potential weaknesses of informed consent.⁶

Regulatory guidelines in the US and Canada warn against undue inducement in the form of “excessively large” payment, but do not provide any sense of what constitutes “excessive.” The fear that payments distort participants’ abilities to assess risks and burdens has little empirical support,⁷ but cannot be ignored. If the HCV CHIM in the course of recruitment begins to suspect that the informed consent process is failing to adequately prepare and inform participants due to the money being offered, then the study can reassess payment practices if informed consent is indeed faulty. The moral costs of payment conservatism, however, are also significant, and should be weighed against the theoretical possibility of undue inducement. 

1. Our consensus statement from February 2023: “Higher compensation is better given the value of the trials and the significant asks made of volunteers over a long time period. … Additional expenses incurred by participation should be considered for reimbursement as well, but ideally, the floor of compensation should be high enough such that it overcomes these considerations.” From October 2023: “We encourage ethicists, researchers, and other stakeholders to consider economic justice when deciding compensation and avoid keeping payment low solely for the sake of theoretically protecting volunteers.” ↩︎
2. As proposed by Neal Dickert and Christine Grady (1999), “What’s the Price of a Research Subject? Approaches to Payment for Research Participation,” New England Journal of Medicine 341. ↩︎
3. See: David DeGrazia and Joseph Millum (2021), A Theory of Bioethics, Cambridge Uni. Press, pp. 105–7. Adil E. Shamoo and David B. Resnik, “Strategies to Minimize Risks and Exploitation in Phase One Trials on Healthy Subjects,” American Journal of Bioethics 6(3): “One can argue that restricting payment to healthy volunteers in phase one trials is exploitative. … Justice demands that all workers, including healthy participants in phase one studies, receive fair compensation for their labor.”Jonathan Anomaly and Julian Savulescu (2019), “Compensation for cures: Why we should pay a premium for participation in ‘challenge studies’,” Bioethics 33(7), p. 795: “The poor are exploited when they are paid too little to do valuable work that involves risk, such as working on high-rise scaffolding or in coal mines. The appropriate response is to ensure minimum safety requirements and to pay a minimum premium for risk … Paying above this is not a problem: it is like paying people more to attract them to other kinds of risky or unpleasant work.” ↩︎
4. Matt Lamkin and Carl Elliott (2018), “Avoiding Exploitation in Phase I Clinical Trials: More than (Un)Just Compensation,” Journal of Law, Medicine & Ethics 46(1): “[T]he insistence on avoiding undue influence by lowering payment undermines the core ethical principle of justice in the selection of subjects … Requiring that payments be kept low virtually ensures that the subject population in paid trials will be disproportionately made up of people with lower incomes.” Moreover, while the Canadian health system differs in key ways, statistics from the United States are informative: healthy volunteers in phase I drug research are disproportionately Black and Hispanic and low-income; see Corey A. Kalbaugh et al. (2021), “Healthy volunteers in US phase I clinical trials: Sociodemographic characteristics and participation over time,” PLoS ONE 16(9). ↩︎
5. Holly Fernandez Lynch (2014), “Human Research Subjects as Human Research Workers,” Yale Journal of Health Policy, Law, and Ethics 14(1), p. 160: While minimum wage laws are common globally, the notion of a maximum wage is rare, and never “is payment limited out of fear that workers will suffer from undue inducement. In fact, when it comes to risky work, many would suggest that workers deserve to be paid substantially more, not less. Higher pay would likely also attract a broader swath of the population to risky work, potentially allowing risks to be more evenly distributed rather than concentrating them on the very worst off.” Eric Lee (2019), “Our flawed approach to undue inducement in medical research,” Bioethics 33(1): “The standard solution attempts to prevent undue inducement by limiting the size of offers. … the standard solution significantly harms those who are the worst off.” ↩︎
6. Emily A. Largent and Holly Fernandez Lynch (2017), “Paying Research Participants: The Outsized Influence of ‘Undue Influence’,” IRB 39(4): “To the extent that an IRB finds itself worrying about undue influence as a matter of course… we suggest that this may be a signal that the IRB is not satisfied by its own analysis of risks and benefits…” ↩︎
7. Stephanie A. Kraft et al. (2019), Exploring Ethical Concerns About Human Challenge Studies: A Qualitative Study of Controlled Human Malaria Infection Study Participants’ Motivations and Attitudes, Journal of Empirical Research on Human Research Ethics 14(1). Cynthia E. Cryder et al. (2010), “Informative inducement: Study payment as a signal of risk,” Social Science & Medicine 70(3). DeGrazi and Miller (2021): “We do not know of data that support the claim that payment worsens decision-making. The limited data that exist … suggest that payment does not impair decision-making.” ↩︎