July 17, 2020
Two recent developments have brought renewed publicity to proposals to conduct human challenge studies to test COVID-19 vaccine candidates: an open letter from the organization 1DaySooner and media reports that Adrian Hill’s Oxford University research group is planning a challenge study, taking advantage of the lack of regulatory oversight of human challenge experiments in the United Kingdom.
The open letter is addressed to Francis Collins, Director of the US National Institutes of Health, and signed by many eminent signatories including Nobel Laureates. It offers three short paragraphs that attempt to explain how challenge studies might accelerate the development of a vaccine for COVID-19, before entering into a much lengthier and more detailed discussion of how challenge studies should be executed.
This imbalance highlights the critical problem with proposals for human challenge experiments: the ethical justification for their conduct relies entirely on the premise that they would speed the development of a safe and effective COVID-19 vaccine. The evidence supporting this premise is thin to non-existent.
For good reason, regulatory agencies require safety data from large numbers of vaccine trial participants over a long period in order to consider licensure. The US Food and Drug Administration (FDA) guidance on COVID-19 vaccine development specifies thousands of participants followed for at least six months after receipt of all immunizations.
It is not clear if the 1DaySooner open letter is proposing challenge studies of this size—the logistics would be daunting, and it is extremely unlikely that they would significantly accelerate vaccine development given efficacy trials are already underway, with several more due to start soon. These large studies will provide data on safety and efficacy in the real world, where a licensed vaccine would be used. Challenge studies would occur in a controlled setting where it would be unknown whether the virus exposure was mimicking how transmission occurs in nature.
Adrian Hill is one of the signatories of the 1DaySooner open letter. Hill’s plans to conduct human challenge studies were disclosed in an article in the Guardian, which offers very little information what the justification might be, stating only:
“Hill said that the challenge trial, beginning either after or in parallel with the phase three trial, could provide complementary information about optimal dosing and administration of the vaccine, as well as being a way to test how long immunity to the virus endures after exposure or vaccination.”
These hypothetical suggestions of what a challenge trial “could” do are unconvincing. There are other—albeit possibly more expensive—ways to optimize dosing and administration and evaluate the duration of immunity.
As community-based organizations that work to promote scientific research literacy and broaden informed participation in clinical trials, we are concerned that proponents of human challenge studies fail to appreciate the potential to exacerbate mistrust of science. This mistrust is widespread and not necessarily irrational—there is a grim historical record of abuse in research, particularly of people of color. The apparent eagerness to embrace putting people at risk of death or other complications—both known and as yet unknown—from COVID-19 threatens to undermine the critical tenet that science now places the highest priority on the welfare of research participants.
Without sound, detailed evidentiary support for the claim that challenge studies will accelerate the development of a safe, effective, accessible vaccine, we strongly believe there is no ethical justification for human challenge experiments.
The one scenario that might alter the ethical equation is global declines in community spread of COVID-19 that would preclude the conduct of real-world vaccine efficacy trials. This scenario is alluded to in the 1DaySooner letter and explicitly considered in a recent paper from researchers involved in the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Vaccines Working Group. Two of our organizations—AVAC and TAG—have proposed Guiding Principles on the Ethical Conduct of SARS-CoV-2 Vaccine Challenge Studies that address this possible future context.
But much as we wish that this was currently an issue, the disastrous mismanagement of the response to the COVID-19 pandemic in the US and a number of other countries means that efficacy trials are going to be feasible for the foreseeable future. Promoting the ethical conduct of scientifically rigorous vaccine efficacy trials should, therefore, remain the priority.