Based on their experience in participating in human challenge studies — technically called the Controlled Human Infection Studies (CHIS) — (where participants are deliberately infected with disease-causing pathogens) and responses from 117 potential participants, the authors of an August 2023 paper have argued that $20,000 for a six-month hepatitis C virus challenge study in the U.S. is “reasonable”.
Among the many contentious ethical issues that riddle the human challenge studies, disproportionate payment amounting to inducements for participation tops the list. The ICMR’s Bioethics Unit, which introduced a consensus policy statement on CHIS, says that payment should take into account the loss of wages and incidental expenses, and the time spent and efforts made while participating in CHIS. But it has made altruism central to participation. “The researcher must evaluate the true nature of altruistic motives to participate and select only altruistic participants that meet the selection criteria of the study,” the policy statement says.
Jake D Eberts, Communications Director at 1Day Sooner and a participant in the Shigella and Zika virus CHIS studies and one of the authors of the August 2023 paper disagrees with ICMR’s policy statement that centres altruistic motives to participate in a CHIS study. “If someone joins a CHIS for the money, as long as they understand the risks, I don’t think that’s inherently bad.” Jake was paid $7,350 for the Shigella CHIS study and less than $5,000 for the Zika study. 1Day Sooner serves as an independent monitor in CHIS so participants can reach out with their concerns and complaints. Dr. Anna Durbin, Professor of International Health at the Johns Hopkins Bloomberg School of Public Health and the principal investigator of the Zika CHIS study says that the payment is based on the time of each visit, the number of specimens collected, and what other studies in the area are paying; she had earlier undertaken dengue human challenge studies.
“Imposing a ceiling on compensation does not actually protect low-income people. What protects low-income people (and everyone) is an informed consent process and an ethics review process that makes sure the risks of the study, whether it is a CHIS or other study, are not excessive, and makes sure that participants understand what they are signing up for. Theoretically, if those two conditions are met, compensation could be extremely high and still be ethical (though that would raise different problems),” says Jake. She says that compensation for the hepatitis C CHIS study will be under $10,000 and not $20,000 as proposed by her and others in the August 2023 paper. “We proposed that figure in part because we think it’s important to start a conversation about why compensation in general for CHIS in the U.S. should be higher,” Jake says.
The Shigella study was to determine if the candidate vaccine (SF2a-TT15) was safe and effective in the prevention of Shigella infection, while the Zika study currently being done is to identify the most suitable virus strain and dose for use in a Zika CHIS. The Zika CHIS will then be used to evaluate the protective efficacy of candidate vaccines prior to evaluation in Phase-2 clinical trials.
“There is definitely a spectrum of motivators [financial and/or altruism] for participants, but the important thing is that we do not set the compensation at a scale that we believe would induce someone to engage in a ‘risk’ that they otherwise would never agree to experience, Dr. Wilbur H. Chen, Professor of Medicine at the University of Maryland School of Medicine, Baltimore, U.S. says in an email to The Hindu. Dr. Chen has conducted human challenge studies for cholera, Campylobacter, Shigella, and enterotoxigenic Escherichia coli (ETEC) in the last five years.
Dr. Durbin says that the payment is based on the time of each visit, the number of specimens collected, and what other studies in the area are paying. Dr. Chen who was the principal investigator of the Shigella study says: “Our approach to the compensation of research participants follows an ethical framework of the Wage-Payment model which provides a payment scheme according to what an unskilled labourer who engages in somewhat risky jobs (e.g., a day labour construction worker) might be paid.” The wage-payment model described in detail in a 1999 paper states that “payment of subjects [should] be on a scale commensurate with that of other unskilled but essential jobs”.
According to this Wage-Payment model and the current U.S. averaged compensation of a day labour construction worker, the following compensation was estimated for the required Shigella study visits — consent/screening visit (two hours, low risk activity, $100), vaccination visit (four hours, high risk activity, $400) x 2 visits scheduled in the study, completion of memory aid (less than one hour, low risk activity, $75) x 2 visits scheduled in the study, each inpatient day (one day, high risk but housing and meals provided, $350/day) x 12 days scheduled in the study, each outpatient clinic visit (two hours, low risk, but spaced far in time over six months making it less convenient, $300) x 6 clinic visits scheduled, end-of-study/last visit “bonus” ($300). This totals to $7,350 for the Shigella study.
“The compensation totals to $7,350 which may appear like a large amount of money but is only provided for the visits and activities that are actually completed,” Dr. Chen points out. “The local IRB [Institutional Review Board] has oversight over the research and also determines whether our compensation rates are set at a level of ‘inducement’. We calculate the compensation based on a somewhat objective set of measures and have made this a standardised compensation across our many different studies.”
Dr. Chen also stresses that the compensation should take into account the cost of living for a day labourer in the location where the study is conducted and not be the same as a low cost of living location in the same country. “This would be very relevant to any studies in India where the compensation scheme should be appropriate for reflecting the local wages for time and risk,” Dr. Chen says.
Paul Zimmer-Harwood from 1Day Sooner who had participated in the malaria and COVID-19 CHIS studies (conducted by University of Oxford) was paid £1,800 and £5,250, respectively. The malaria study was to determine whether the adjuvant called Matrix M was suitable for use in the new vaccine R21 that was under development then (now rolled out in Africa), while the COVID-19 CHIS was a phase-1 dose escalation study.
“The remuneration is proportional to the number of study visits and the duration spent in the quarantine unit, rather than the inherent risks of the study. In the U.K., it is a strict guideline that compensation should not incentivise risk-taking behaviour but should instead be commensurate with the time and commitment a participant invests in the study,” says Paul in an email to The Hindu. “The compensation paid to participants in a study like the Malaria CHIS is decided based on the duration of the study, the number of visits required, the level of inconvenience. The aim is to compensate participants for their time and effort, not to pay for the risk they are taking.” He was isolated for five days before being exposed to SARS-CoV-2 virus and 14 days after the challenge, while the malaria CHIS study, inclusive of all follow-ups, extended over a period of one year.
