Ethical Guidelines for Deliberately Infecting Volunteers with COVID-19

Abstract

Global fatalities related to COVID-19 are expected to be high in 2020-21. Developing and delivering a vaccine may be the most likely way to end the pandemic. If it were possible to shorten this development time by weeks or months, this may have a significant effect on reducing deaths. Phase 2 and Phase 3 trials could take less long to conduct if they used human challenge methods – that is, deliberately infecting participants with COVID-19 following inoculation.This article analyses arguments for and against such methods and provides suggested broad guidelines for regulators, researchers and ethics committees when considering these matters. It concludes that it may be possible to maintain current ethical standards yet still permit human challenge trials in a context where delay is critical. The implications are that regulators and researchers need to work together now to design robust but short trials and streamline ethics approvals processes so that they are in place when applications for trials are made.

Vaccines for COVID-19

“…As animal models do not fully recapitulate human disease, alternative strategies may be required. Controlled human infection models (CHIM) are studies in which participants (either vaccinated or not) are intentionally challenged with an infectious organism [86]. CHIM trials of SARS‐CoV‐2 vaccine candidates could be particularly beneficial in vaccine and drug efficacy studies, especially if the community infection rate has declined due to epidemiological interventions [87].…”

Adaptive treatment allocation and selection in multi-arm clinical trials: a Bayesian perspective

“…To overcome this problem, it would therefore be almost mandatory to seek regulatory approval to a design in which healthy volunteers, some vaccinated by the candidate and some by an already approved vaccine, say Vaccine*, used as a control treatment, are exposed to the virus under a carefully specified protocol. The possibility of a human challenge design, albeit with placebo controls, was already discussed at the time when no efficacious vaccine was available (World Health Organization 2020, Eyal et al 2020, Richards 2020, and it is still considered relevant now (Eyal and Lipsitch 2021). One could anticipate that in a challenge trial, naturally depending on the level of viral exposure that would be applied, a much smaller number of participants would be needed for reaching a statistically valid conclusion on comparability.…”

Broad cross-national public support for accelerated COVID-19 vaccine trial designs

“…While technical questions also surround the use of these and related approaches in COVID-19 vaccine testing [8] , [9] , [10] , [11] , several of the roadblocks to their implementation depend in part on the answer to an empirical question: would members of the general public see these designs as ethical [12] , [13] , [14] , [15] , [16] ?…”

“…First, there has been considerable debate about the ethics of accelerated designs for COVID-19 vaccine trials, particularly human challenge trials [3] , [8] , [13] , [14] , [15] , [16] , [17] , [18] . Ethicists have held that part of what determines whether proposed research is ethical are societal attitudes toward that research, especially among those individuals and communities who will be most affected by it [19] .…”