Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the “risk-escalation model,” establishes a moral principle that should guide decision-making in early-phase trials.


Additional Information

Print ISSN
pp. 121-139
Launched on MUSE
Open Access
Back To Top

This website uses cookies to ensure you get the best experience on our website. Without cookies your experience may not be seamless.