Research Ethics for Emerging Trial Designs: Does Equipoise Need to Adapt?

Emerging trial designs—including umbrella and basket trials, adaptive platform trials, and cluster randomized trials—present new challenges for applying Freedman’s 30-year-old concept of clinical equipoise, which was formulated in the context of traditional 2-arm RCTs and requires uncertainty about the relative merits of each trial arm. The authors propose developing specific guidelines to help ethics committees and trialists evaluate equipoise in the context of these new designs and biomarker-driven approaches, and to optimize risk communication with trial participants.