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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[i] and media reports that Adrian Hill’s Oxford University research group is planning a challenge study[ii], 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 U.S. 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 U.S. 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.[iii]
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.[iv] 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.[v]
But much as we wish that this was currently an issue, the disastrous mismanagement of the response to the COVID-19 pandemic in the U.S. 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.
AIDS Action Baltimore
AIDS Foundation Chicago
AIDS Project of the East Bay
Associação Alternativa Terrazul
Black AIDS Institute
Coalition for Health Promotion and Social Development (HEPS Uganda)
Comitê Comunitário de Acompanhamento em pesquisas de Tuberculose Brasil – CCAP TB Brasil
European AIDS Treatment Group (EATG)
Foaesp (Fórum das Ong Aids do estado de São Paulo)
GIV (Group for Life Incentive) São Paulo (SP)
Grupo de Trabajo sobre Tratamientos del VIH (gTt-VIH)
Institute of HIV Research and Innovation
IRMA – International Rectal Microbicide Advocates
Latino Commission on AIDS
Love To Love Organization
MSM Asis Google Group
Nigerian Women Agro Allied Farmers Association
Red Ribbon Istanbul
RNP + Belo Horizonte MG
RPCSTB- Rede Paulista de Controle Social da Tuberculose
Taraba State AIDS Control Agency, TACA
Thailand National HIV CAB
Treatment Action Group
Vivir. Participacion, Incidencia y Transparencia, A.C.
TAG CONTACT: Richard Jefferys, email@example.com
[ii] Devlin H. Coronavirus vaccine: Oxford team aim to start lab-controlled human trials. 2020 July 16. https://www.theguardian.com/science/2020/jul/16/coronavirus-vaccine-oxford-team-volunteers-lab-controlled-human-challenge-trial
[iii] U.S. Department of Health and Human Services, Food and Drug Administration Center for Biologics Evaluation and Research.. Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry. 2020 June. https://www.fda.gov/media/139638/download
[iv] Deming ME, Michael NL, Robb M, Cohen MS, Neuzil KM. Accelerating Development of SARS-CoV-2 Vaccines – The Role for Controlled Human Infection Models. N Engl J Med. 2020 Jul 1. doi: 10.1056/NEJMp2020076. Online ahead of print.