More than a moment: Evolving decisions among eligible volunteers in phase 1 COVID-19 vaccine trials

Abstract

ABSTRACT Phase 1 vaccine trials rely on healthy participants who accept uncertainty with limited or no personal health benefit. Why people join and why they stay until trial completion is underexplored. Using a modified grounded theory approach, we examined decision making among eligible individuals who enrolled (trial participants (TPs), n = 32) and those that declined enrollment (non-participants (NPs), n = 5) across two phase 1 COVID-19 vaccine trials conducted during the pandemic (Nova Scotia, Canada; 2021–2023). Semi-structured qualitative interviews were carried out at enrollment or non-enrollment (both groups) and trial completion (TPs only). Transcripts were analyzed with open, focused, and theoretical coding, constant comparison, and memo writing to develop a grounded conceptual account of decision making during a trial. Analysis revealed a core analytic category, Harmonizing Self and Circumstances Amid a Pandemic. Within this broader category, two overlapping and interconnected categories of decision making emerged: Deciding Whether to Enroll, that involved balancing personal benefits, circumstances, and altruistic aims and; Revisiting Participation as Circumstances Changed, shaped by the rollout of Public Health approved vaccines (PHAVs), vaccine mandates, and COVID-19 case counts. A mid-trial protocol adaptation allowing participants to receive a PHAV supported retention until trial completion. NPs prioritized immediate access to a PHAV. Participation in phase 1 vaccine trials was a fluid process rather than a single decision, where motivations, concerns, and priorities were continuously reevaluated with shifting personal, trial, and pandemic circumstances. Future trials should anticipate changing contexts, communicate clearly about informed consent and data integrity when standard-of-care vaccines emerge, and incorporate flexible trial adaptations.