Ethics and equipoise in a phase I COVID-19 vaccine trial

Abstract: During the COVID-19 pandemic, SARS-CoV-2 vaccines were designed and tested with unprecedented speed. In the US, after authorized vaccines became widely available, enrollment of vaccine-naïve individuals in COVID vaccine trials became ethically and practically challenging. The continuance of placebo-controlled early phase vaccine trials raised questions about risks and benefits since participants were asked to forgo proven vaccines. We conducted a qualitative interview study of community members in a first-in-human phase I COVID vaccine trial at a time when EUA vaccines became widely available. Many participants were exceptionally motivated to help fight the COVID public health crisis. Interviewees described thoughtful consideration of risks of forgoing proven vaccines and undertaking early phase research. Trial participants differed from decliners in their tolerance for COVID risk in the community and/or their COVID vaccination requirements for work, school, or travel. Most trial participants expressed altruistic motivations and keen interest in supporting vaccine research. Ethical challenges have led to debates regarding use of placebos and the related question of forgoing standard medical interventions to receive an investigational product. Our data are reassuring in that study participants were well aware of risk/benefit tradeoffs, however the findings also raise the question of determining an acceptable cutoff for risk when there are still (a few) informed and willing volunteers. The risk/benefit calculus that potential enrollees undertook provides a new lens through which to view ethical discussions of what researchers ought to communicate about research, and when placebo -controlled studies may be considered ethically appropriate.

Kimberly Acosta – Walter Reed Army Institute of Research; Jael Kagai – Community Engagement – Walter Reed Army Institute of Research