Evolving ethics of COVID-19 challenge trials

Abstract

The Personal View by Euzebiusz Jamrozik and Michael Selgelid1Jamrozik E Selgelid MJ COVID-19 human challenge studies: ethical issues.Lancet Infect Dis. 2020; (published online May 29.)https://doi.org/10.1016/S1473-3099(20)30438-2Summary Full Text Full Text PDF PubMed Scopus (65) Google Scholar was helpful in laying out some of the key ethical issues with human challenge trials for COVID-19. This response provides both an alternative perspective and an updated viewpoint about the ethical tradeoffs involved. In short, because of the urgency of the situation, the landscape has evolved significantly, even in the past month, and many experts feel the ethical concerns voiced can now be addressed.21DaySoonerChallenge trials for COVID-19, an open letter to Dr Francis Collins.https://1daysooner.org/openletterDate: July 15, 2020Google Scholar WHO has now published criteria for ethical acceptability of conducting human challenge trials.3WHOKey criteria for the ethical acceptability of COVID-19 human challenge studies.https://www.who.int/ethics/publications/key-criteria-ethical-acceptability-of-covid-19-human-challenge/enDate: May 6, 2020Date accessed: May 6, 2020Google Scholar Their advisory group, of which Jamrozik was a member, recently published a report outlining the feasibility and value of such trials.4WHO Advisory Group on Human Challenge StudiesFeasibility, potential value and limitations of establishing a closely monitored challenge model of experimental COVID-19 infection and illness in healthy young adult volunteers.https://www.who.int/publications/m/item/feasibility-potential-value-and-limitations-of-establishing-a-closely-monitored-challenge-model-of-experimental-covid-19-infection-and-illness-in-healthy-young-adult-volunteersDate: June 15, 2020Date accessed: June 21, 2020Google Scholar So as Jamrozik and Selgelidsuggested, public engagement and consultation with regulatory groups is critical, and now the results of that engagement are beginning to appear.5Broockman D Kalla J Guerrero A et al.Broad cross-national public support for accelerated COVID-19 vaccine trial designs.OSF Preprints. 2020; (published online July 15.)https://doi.org/10.31219/osf.io/au3fqGoogle Scholar Jamrozik and Selgelid also discuss public benefits of human challenge trials for COVID-19, which are far clearer than they appeared to be even a few months ago. One issue that concerned 11 of the 19 WHO advisors was that results for younger volunteers might not be a valid predictor of efficacy. Not only is there a substantial minority who disagree, but there are a variety of uses of human challenge trials other than deriving estimates of vaccine effectiveness.6Nguyen LC Bakerlee CW McKelvey TG et al.Evaluating use cases for human challenge trials in accelerating SARS-CoV-2 vaccine development.Clin Infect Dis. 2020; (published online July 6.)https://doi.org/10.1093/cid/ciaa935Crossref Scopus (17) Google Scholar Moreover, even if one or more vaccines was found to be efficacious only in healthy younger populations via a human challenge trial, this would still be useful in conjunction with other vaccines, since more than one vaccine is likely to be necessary, and healthy-population vaccines will help in ensuring sufficient supplies of other vaccines for higher-risk populations. Such a vaccine would also be economically beneficial through allowing a large group of people to return to the workforce. There are some remaining issues, but they are less critical. For example, the majority of the WHO advisory board believed that a trial could proceed without any rescue therapy. Even if not, however, the pace of development and testing of therapies makes it seem increasingly likely that some therapies will be available by the time a trial would start. We cannot be certain that human challenge trials will accelerate vaccine development and save lives. We do claim that it is likely they would, if used. The benefits of these trials would not excuse ethical shortcuts, which no-one advocates, but they do make the cost of excessive caution clear. There is a window of opportunity for debate that is closing, and discussion should continue, but delays in planning challenge trials because of potentially addressable ethical concerns seem, if not unethical, at best unwise. I declare no competing interests. COVID-19 human challenge studies: ethical issuesCOVID-19 poses an extraordinary threat to global public health and an effective vaccine could provide a key means of overcoming this crisis. Human challenge studies involve the intentional infection of research participants and can accelerate or improve vaccine development by rapidly providing estimates of vaccine safety and efficacy. Human challenge studies of low virulence coronaviruses have been done in the past and human challenge studies with severe acute respiratory syndrome coronavirus 2 have been proposed. Full-Text PDF