Factors influencing participation in controlled human infection models: a pooled analysis from six enteric fever studies

Abstract

Background: Enteric fever is an acute febrile-illness caused by infection with the human-restricted Salmonella serovars Typhi and Paratyphi. Controlled human infection models (CHIM) of S. Typhi and Paratyphi infection are used to accelerate vaccine development and to better understand host-pathogen interactions. The primary motivations for participants to take part in these studies are unknown. We studied participant motivations, attitudes and the factors influencing CHIM study participation. Methods: Participant surveys were nested in six enteric fever CHIM studies conducted at a single centre in Oxford, UK, between 2011 and 2017. All eligible participants received one invitation to complete an anonymous, self-administered paper or online survey on either day 28 or 60 after challenge. A descriptive analysis was performed on these pooled data. All studies were included, to minimize selection bias. Results: Survey response rates varied from 33.0%-86.1%, yielding 201 participants. In the cohort, 113/198(57.0%) were educated to bachelor’s level, 61.6% were employed, 30.3% were students and 4.6% were unemployed. The most commonly cited motivations for CHIM study participation were a desire to contribute to the progression of medicine (170/201; 84.6%); the prospect of financial reimbursement (166/201; 82.6%) and curiosity about clinical trials (117/201; 57.2%). The majority of respondents (139/197; 70.6%) reported that most people advised them against participation. Conclusion: Motivation to participate in a CHIM study was multi-factorial and heavily influenced by internal drivers beyond monetary reimbursement alone. High educational attainment and employment may be protective factors against financial inducement; however, further research is needed, particularly with CHIM studies expanding to low-income and middle-income countries.

Payment in challenge studies: ethics, attitudes and a new payment for risk model

“…53 Similarly, studies looking at motivations of CHIM participants in the UK, which still experience infectious diseases although at lower rates than LMICs, found that the 'desire to contribute to the progression of medicine' was the biggest motivator for CHIM participation, even above monetary compensation. 54 The COVID-19 pandemic has been a cruel reminder that infectious diseases can cause immense economic, social and health impacts from which no country is immune. Hence, it would be reasonable to assume that many, if not all, of those signing up to partake in the COVID-19 CHIM are strongly motivated to find a vaccine that will save lives and allow society to go back to normal, over and above any financial compensation they will receive.…”

Promoting Ethical Payment in Human Infection Challenge Studies

“…Importantly, even when healthy participants are motivated by money, available data indicate that perceived risk is their ultimate deciding factor, and they will avoid studies they perceive to be too risky. These findings about motivation and decision-making among healthy participants in general are largely replicated in studies specific to HICS (Njue et al 2018;Kraft et al 2019;Oguti et al 2019;Jao et al 2020). HICS participants report that they engage in substantial deliberation before deciding to enroll, are not worried about study risks (perhaps unsurprisingly, given low risk of serious long-term harm in traditional HICS involving treatable diseases), and would consider participating again.…”

“…Another consideration when setting payment offers may be the stigma that sometimes accompanies HICS participation. Some HICS participants, for instance, report experiencing negative responses from family and friends or keeping their participation secret due to concerns about how it may be perceived (Roth 2007;Njue et al 2018;Kraft et al 2019;Oguti et al 2019;Hoogerwerf, de Vries, and Roestenberg 2020;Jao et al 2020). Even if the stigma is associated with perceived mercenary risktaking for money, however, that would be insufficient reason to reduce fair payment; the same is true to the extent that paying HICS participants might negatively influence public trust in this type of research.…”

Should practice and policy be revised to allow for risk-proportional payment to human challenge study participants?

“…Euzebiusz Jamrozik , 1,2,3 Michael J Selgelid 1 Human infection challenge studies (HCSs) 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.…”

“…Grimwade et al 1 add to previous public engagement, qualitative evidence and philosophical literature on these topics. [1][2][3][4][5][6][7][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.…”