By Olivia Grimwade and Julian Savulescu.

Controlled Human Infection Model (CHIM) research involves infecting otherwise healthy people with a disease in order to improve our knowledge of the disease and/or to test vaccine candidates. In the hope of halting the deaths, infections and lockdowns caused by the COVID 19 pandemic, CHIMs have been identified as a method to fast-track COVID vaccine research. CHIMs have previously been ethically performed with a variety of other diseases, such as Malaria, although the ethical permissibility of a COVID CHIM is still up for debate because of the risks involved. Despite this, there is still growing support for COVID CHIMs with over 30,000 volunteers indicating interest in being participants in these studies.

If we assume that a COVID CHIM is ethical to perform, how much would you expect to be paid for being a participant? Do you think that you ought to be paid for the risk involved? What do CHIM participants generally get paid anyway? And how should we go about determining ethical payment for CHIM participants? These are the sorts of questions that prompted our partly empirical and partly philosophical study into payment in CHIMs (soon to be published on JME).

Payment in CHIMs is a highly contentious issue which has previously attracted a lot public interest. The central concerns raised in regard to payments are that high payments could be coercive (force participants to take part in a study) or an undue inducement to participants (make them misjudge the risks involved). It’s difficult to understand how the offer of payment could be coercive as participants always have the alternative of turning down any offer to partake in a study, or payment, or they could decide to donate it to charity. Offers of payments broaden, rather than restrict, the range of options available to participants. Undue inducement may seem like a more valid concern in theory; however, studies have failed to show that money distorts our judgement of risks in practice. Also, we don’t think of undue inducement as a concern when it comes to payment for other risky jobs, so why should we treat CHIM participation differently? Despite the increasing number of arguments challenging these concerns, many research guidelines advise researchers to limit payments to avoid the risks of coercion and undue inducement. We instead have a different concern: that the current payments are too low and are at risk of exploiting participants by not fairly compensating them for the risks involved.

We surveyed a group of CHIM experts and found that there is great variation in the payment offered for CHIM participation with some participants offered no money at all while others offered over £3000. CHIMs differ in terms of the time requirements, burdens and risks they put on participants, so this could explain some of the differences in payment. However, even similar studies reported paying very different amounts. This may suggest that it is the consideration of different factors when determining payment that is driving the differences. We also asked the CHIM experts and a group of UK citizens what they believe a participant should be paid for partaking in a series of hypothetical CHIMs that varied in terms of the risk involved. We found that both groups believe CHIM participants should be paid a considerable amount of money for their involvement. The UK citizens indicated CHIM participants should be paid approximately triple the UK minimum wage and the experts indicated they should be paid more than double the UK minimum wage. Currently, most CHIM participants are only paid for time and inconvenience, not the risks they take on. We argue that participants should be paid for risk, just as other workers are paid “danger money” for particularly risky jobs. UK citizens also thought that participants should be paid for the risk they endure throughout participation although the experts were more divided on the payment for risk.

A standardised ethical framework for payment in CHIMs would greatly benefit the CHIM research field. It would allow researchers to have more confidence in their practice, it would allow participants to be more confident that they are being appropriately compensated and the increased transparency about payment in CHIMs is likely to decrease societal fears surrounding the payment of CHIM participants. We propose a new Payment for Risk Model which involves paying for time, pain, inconvenience and for the risk associated with participation. We believe this model is the most likely to lead to fair payment for CHIM participants particularly as it fairly compensates them for accepting risk for the public good. Although it may be difficult to assign a monetary value to pain or risk, there are ways that it could be done. We explore two methods that could be used to determine extra payment for risk. The first is similar to how risk and pain is compensated for in other employment and the second is using the value of statistical life to calculate bonus risk money.

With the growing number of CHIMs currently being performed and the increasing calls for COVID-19 CHIM research, it is crucial we ensure CHIM participants are fairly compensated for the part they play in advancing medical research. Our study has provided novel data describing current payment practices and the attitudes towards payment to inform discussions around payment in CHIM. We have also proposed a Payment for Risk Model that could be used to determine ethically justified payment for CHIM participants. This payment model is not only valuable for determining payment in CHIMs but could be used to guide payment in other areas of research.

Paper title: Payment in challenge studies: ethics, attitudes and a new Payment for Risk model

Authors: Olivia Grimwade^1,2, Julian Savulescu^2,3, Alberto Giubilini^2,4, Justin Oakley⁵, Joshua Osowicki^6,7, Andrew J Pollard⁸, Anne Marie Nussberger⁹

Affiliations:

1. Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
2. Faculty of Philosophy, University of Oxford, Uehiro Centre for Practical Ethics, Oxford, UK
3. Murdoch Children’s Research Institute, Parkville, Victoria, Australia
4. Wellcome Centre for Ethics and Humanities, Oxford, UK
5. Monash University Bioethics Centre, Melbourne, Victoria, Australia
6. Tropical Diseases Research Group, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
7. Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia
8. Department of Paediatrics, University of Oxford, Oxford, UK
9. Department of Experimental Psychology, University of Oxford, Oxford, UK

Competing Interests: AJP and J Osowicki are both CHIM investigators. J Osowicki is an investigator on CHIM studies funded by the Australian NHMRC & Medical Research Future Fund (MRFF). AJP is a CHIM investigator and co-director of the UK MRC Hic-Vac network. AJP is Chair of UK Dept. Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) and is a member of the WHO’s SAGE. AJP is an NIHR Senior Investigator. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO.

Social media accounts: @OliviaGrimwade and @juliansavulescu