AbstractDuring the Covid-19 pandemic, ethicists and researchers proposed human challenge studies as a way to speed development of a vaccine that could prevent disease and end the global public health crisis. The risks to healthy volunteers of being deliberately infected with a deadly and novel pathogen were not low, but the benefits could have been immense. This essay is a history of the three major efforts to set up a challenge model and run challenge studies in 2020 and 2021. The (...) pharmaceutical company Johnson and Johnson, the National Institutes of Health in the United States, and a private-public partnership of industry, university, and government partners in Britain all undertook preparations. The United Kingdom’s consortium began their Human Challenge Programme in March of 2021.Beyond documenting each effort, the essay puts these scientific and ethical debates in dialogue with the social, epidemiological, and institutional conditions of the pandemic as well as the commercial, intellectual, and political systems in which medical research and Covid-19 challenge studies operated. It shows how different institutions understood risk, benefit, and social value depending on their specific contexts. Ultimately the example of Covid-19 challenge studies highlights the constructedness of such assessments and reveals the utility of deconstructing them retrospectively so as to better understand the interplay of medical research and research ethics with larger social systems and historical contexts. (shrink)

In controlled human infection (CHI) studies, investigators deliberately infect healthy individuals with pathogens in order to study mechanisms of disease or obtain preliminary efficacy data on investigational vaccines and medicines. CHI studies offer a fast and cost‐effective way of generating new scientific insights, prioritizing investigational products for clinical testing, and reducing the risk that large numbers of people are exposed to ineffective or harmful substances in research or in practice. Yet depending on the pathogen, CHI studies can involve significant risks (...) or burdens for participants, pose risks to individuals or communities not involved in the research, and lead to public controversy. It is therefore essential to ensure that the risks of CHI studies are justified by their social value—that is, their potential to generate benefits for society—and that public trust can be maintained. In this paper, we aim to clarify how research sponsors, research ethics committees and other reviewers should judge the social value of CHI studies. We develop a list of relevant considerations for making social value judgments based on the standard view of social value. We then use this list to discuss the example of potentially conducting dengue virus CHI studies in endemic settings. We argue that dengue virus CHI studies in endemic settings would fall on the higher end of the spectrum of social value, mostly because of their potential to redirect all fields of future dengue research. Drawing on this discussion, we derive several general recommendations for how reviewers should judge the social value of CHI studies. (shrink)