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.

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We thank the authors of the 5 commentaries for their careful and highly constructive consideration of our paper [1] which has enabled us to develop our proposal. General PointsParticipation 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 (CHIM) research or "challenge studies", is that they are unpleasant and time consuming. Researchers want to offer carrots to incentivise participation (as Fernandez Lynch and Largent suggest [2]).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, Ockenfel 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: "(1) salary for time involvement that is adjusted to account for the amount of discomfort experienced during participation, (2) insurance against ex post adverse outcomes and (3) ex ante compensation for risks that cannot be compensated ex post (such as death)." [3] This effectively addresses Lynch and Largent's [2] concern (echoed by Jamrozik and Selgelid [4]) 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, Ockenfel and Roth convincingly argue [3].