Adaptive clinical trials and master protocols

Methodologies for randomized, double-blind, placebo-controlled clinical trials continue to develop in concert with evolving scientific and translational knowledge. Adaptive trial designs, in which data generated during the study are used to modify subsequent study activity (i.e., sample sizes, entry criteria, or outcomes), can optimize flexibility and expedite the safety and efficacy assessments for interventions of interest. This chapter will summarize general designs, advantages, and pitfalls associated with adaptive clinical trials and compare their features with those of conventional trial designs. It will also review novel ways for which seamless designs and master protocols may improve trial efficiency while offering interpretable data.