Challenge studies for COVID-19: Now is still not the time

By Françoise Baylis and Landon J Getz

Two challenge studies for COVID-19 involving the deliberate infection of healthy volunteers aged 18-30 are underway in the UK. Both studies involve the original strain of SARS-CoV-2 from Wuhan China, and not the recent variants of concern – commonly referred to as B.1.1.7, B.1.351 and P.1. These variants seem to spread more easily and quickly, evade natural or vaccine-related immunity and cause more severe illness. We believe these challenge studies are at best premature.

The first trial, approved in February 2021, aims to determine the dose at which a person deliberately exposed to SARS-CoV-2 becomes infected. The second trial, which starts in April 2021, studies immune responses among those who have previously been naturally infected with SARS-CoV-2.

For the past six months, many (including ourselves) have argued that COVID-19 challenge trials are unethical at least until such time as there are reliable rescue therapies, as is the norm for most risky human challenge trials. As such, we note with interest that the participants in the second trial will be given Regeneron monoclonal antibody treatment if they develop symptoms. No such plans were announced with the first approved challenge trial.

Our most recent arguments against the first study were published about a month ago in the Journal of Medical Ethics blog. There we highlighted the risk of serious harm (including Long COVID) or death, the absence of a clear favourable harm-benefit ratio relative to the stated goal of “understanding how the virus affects people”, and challenges with informed choice. In addition, we questioned the underlying presumption that it is fair and reasonable to ask youth to assume the risks of trial participation mostly for the potential benefit of an older population that for years has systematically failed to protect their interests.

Abie Rohrig and David Manheim contest our position. While there is much in their commentary that deserves a response, a comprehensive rebuttal would require an article of considerable length and so we restrict our comments to a few salient points.

In our original post, we refute the suggestion that participation in risky challenge trials is analogous to the risky work done in the armed forces, law enforcement and firefighting. While all of these activities entail an (albeit small) risk of death, paid trial participation is at best precarious work, not professional employment. It does not come with benefits, job security, the potential to collectively bargain and so on. As such, these activities are not analogous. In response, Rohrig and Manheim suggest that we have failed to account for organ donors “who take a medical risk without a minimum wage, the power to collectively bargain, or opportunities for career advancement.”

From our perspective, organ donation is also not analogous to participation in a challenge trial. Most organ donations are cadaveric. Live organ donations are most often between close relations and friends. Only very exceptionally are the risks of live organ donation assumed for the benefit of strangers. So perhaps Rohrig and Manheim have a point here: it would appear that challenge trial participation is analogous to this type of organ donation: in both instances, risks are altruistically assumed for the benefit of strangers. There is an important difference, however. In Western democracies, organ donation is to be a purely altruistic act; we do not pay organ donors. Participation in the UK COVID-19 challenge trial is not a purely altruistic act. Participants are remunerated and there is reason to believe that without remuneration (around £4,500) many would not participate. Moreover, without remuneration as a potential benefit, the harm-benefit ratio of the trial would be sufficiently less favourable as to call into question the ethics of the trial.

A recent empirical study by an interdisciplinary team of ethicists, philosophers, clinical trial technicians and statisticians on motivation for participation in phase 1 vaccine trials where there is no perceived benefit to participation is instructive. This study included trial participants in a phase 1 Ebola vaccine study and a phase 1 adjuvanted seasonal influence vaccine study. It confirmed that while altruism (a desire to “give back” or to contribute to science and/or medicine) plays a part in the motivation to enroll in early phase vaccine studies, so too does the desire to receive financial compensation or other incentives. While we agree with Rohrig and Manheim that “benefits to individuals should not be understood purely in financial terms,” this does not mean that the promise of financial benefit to volunteers is unimportant in considering the ethics of the ask.

Further, Rohrig and Manheim suggest that prohibiting challenge trials is somehow “an affront to the agency of volunteers.” We interpret this to mean that youth are capable of making autonomous choices about trial participation and that when they do so their choices should be respected. We don’t disagree with this claim, but autonomy is about more than freedom from interference. A meaningful exercise of autonomy presumes certain background social conditions. This explains why we included information about the level of remuneration for trial participation, and the high rate of unemployment among those in the target population. We estimate, for example, that an offer of around £4,500 for a few weeks of trial participation to someone living below the poverty line likely has an impact on voluntariness.

In sum, we reiterate our conclusion that at this time, ethical issues regarding serious risk of harm, trial design, informed choice, and justice plague COVID-19 human challenge studies, and ought to preclude their progression.

 

Authors: Françoise Baylis, Landon J Getz*

Affiliations:

Françoise Baylis is University Research Professor at Dalhousie University in Halifax. She is a member of the Order of Canada and the Order of Nova Scotia, as well as a fellow of the Royal Society of Canada and of the Canadian Academy of Health Sciences. Baylis is the author of Altered Inheritance: CRISPR and the Ethics of Human Genome Editing.

Landon J. Getz is a Ph.D. Candidate, Vanier Scholar and Killam Laureate in the Thomas Lab, Department of Microbiology and Immunology at Dalhousie University

Social media accounts of post authors:

Twitter: @landongetz @francoisebaylis

Competing interests: None declared

*Corresponding Author

 

 

 

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