Innovations in Early-Phase Adaptive Trial Designs for Stroke Research

Stroke can occur at any age, and the effects can last for the remaining lifetime. To minimize the clinical and economic burden of stroke, we need to develop and test new treatments that have the potential to improve outcomes for people with stroke. Early-phase trials are foundational to testing new treatments in medicine. Early-phase trials encompass dose-ranging, dose-screening, and dose-finding noncomparative designs. A dose-ranging trial aims to establish the safe and tolerable dose range for a given investigational intervention in a target population to progress to a dose-screening or dose-finding trial that systematically identifies an intervention dose(s) in the target population that has a signal of efficacy, feasibility, safety, and tolerability. Such designs originated in the oncology field and are gaining prominence in stroke literature. In this article, we first outline the features that differentiate the contribution of early-phase trials from late-phase trials and present a stepwise development program approach to frame our discussion. We then review early-phase trial terminology, discuss the characteristics of early-phase trials and high-quality reporting, and the role, value, and contribution of early-phase trials across the continuum of stroke care using published and ongoing trial examples. Finally, we highlight emerging innovations in early-phase trial design and application to inform future work in stroke.