By Abie Rohrig and David Manheim.

In a recent blog post, Nix and Weijer argue that living kidney donation and volunteering for a COVID-19 challenge trial are disanalogous, and that “advocates of SARS-CoV-2 challenge studies must look elsewhere to justify the level of risk in these studies.” They offer three arguments to support this view: adverse effects are better understood for kidney donations, challenge trials have fewer risky alternatives, and challenge trials are more liable to undermine public trust in science.

These arguments are well-considered, and we strongly agree that the possibility of an adverse event in a challenge trial makes it imperative to clearly communicate both the purpose of these trials and the risks and benefits to the public. But no analogy between scientific and medical interventions will be perfect, and the question of whether challenge trials are worthwhile is not based on analogies. It is based on analysis of the substantive question: is this a justifiable risk?

The case for challenge trials has never rested on an analogy.

It is unfortunate that a useful analogy for risks is being misinterpreted as a justification. Risk communication has long found that analogies and comparisons are helpful for public understanding. These analogies are separate from the analysis and justification of the risk itself, which in this case is that we ought to allow fully informed and consenting volunteers to participate in challenge trials for the public benefit. It is difficult to imagine a society in which firefighters and search-and-rescue teams are forbidden from entering dangerous terrains on the grounds that the risks are uncertain. Given that the known risks are made clear to volunteers, and the life-saving benefits are probable, the altruistic decision should rest in the hands of the volunteers.

Living kidney donations were not always so well-understood or well accepted

Nix and Weijer argue that we know the long-term effects of kidney donation and not challenge trials, but this was not always the case. We had no data on the long-term effects of living kidney donations when we first started performing this procedure  in the 1950s. Certainty has not, and never will be, a viable criteria in medical or public health decision-making; in fact, we are in a catch-22 if we need long-term data before trying anything new. Our best understanding of the short-term and long-term risks of COVID-19 for young, healthy people are low enough to warrant a trial.

Similarly, as Nix and Weijer note, organ donation has not always been as publicly accepted as it now is. The argument that public trust is fragile could easily have been applied to kidney donation in the past.

The world needs more and better vaccines

Nix and Weijer argue that the unprecedented speed of conventional Phase III efficacy trials obviate the need for COVID-19 challenge studies. But absent more and better vaccines, the developing world will remain unvaccinated for quite a long time. Amnesty International has warned that, due to supply constraints and vaccine pre-purchases from wealthy countries, 9 of 10 people in poor countries won’t get vaccinated in 2021. As the UK Vaccine Taskforce recently wrote, “challenge trials will be a critical method of “select[ing] most promising vaccines faster and optimising investment,” especially if low transmission rates mean that  “large-scale field efficacy studies simply may not exist.” Accelerating the licensure of single-dose, intranasal vaccines like Codavax-COVID by even a few days will save lives. Challenge trials can also uniquely reveal important data on COVID-19 pathogenesis, duration of natural and vaccine-induced immunity, and information on whether vaccines prevent viral transmission.

Public trust can be enhanced, not harmed, by challenge trials

We agree that public trust in vaccines is critical, and would certainly oppose anything that would undermine trust in vaccines, since the damage of doing so could be far greater than even the vast short-term benefits of accelerating availability of vaccines for COVID-19. Hesitating to allow the research might also undermine trust in science as populations wait longer than necessary for vaccines to be approved. Studies show that openness about risks is far more effective than paternalism for building public trust. Challenge trials have risks that are clearly accepted by volunteers,  and the public supports challenge trials.

Conclusion

The kidney donation-challenge trial volunteer analogy, while imperfect, illustrates an important point: those who wish to take justifiable, sufficiently understood, and relatively small risks to save lives should be celebrated, not belittled. Opposition to challenge trials on the basis of objecting to an analogy, however, seems much more difficult to justify.

Authors: Abie Rohrig and David Manheim

Affiliations:

AR: Communications Director, 1Day Sooner, New York City, USA

DM: Health and Risk communication Research Center, University of Haifa, School of Public Health, Haifa, Israel

Competing interests: None declared.