B1684
Title: Dynamic enrichment of small sample, sequential, multiple assignment randomized trial (snSMART) design
Authors: Satrajit Roychoudhury - Pfizer Inc. (United States) [presenting]
Abstract: In Duchenne muscular dystrophy (DMD) and other rare diseases, recruiting patients into clinical trials is challenging. Additionally, assigning patients to long-term, multi-year placebo arms raises ethical and trial retention concerns. This poses a significant challenge to the traditional sequential drug development paradigm. A small sample, sequential, multiple assignment, randomized trial (snSMART) design is discussed, that combines dose selection and confirmatory assessment into a single trial. This multi-stage design evaluates the effects of multiple doses of a promising drug and rerandomizes patients to appropriate dose levels based on their stage 1 dose and response. The proposed approach increases the efficiency of treatment effect estimates by i) enriching the placebo arm with external control data, and ii) using data from all stages. Data from external control and different stages are combined using a robust meta-analytic combined (MAC) approach to consider the various sources of heterogeneity and potential selection bias. Data is reanalyzed from a DMD trial using the proposed method and external control data from the Duchenne Natural History Study (DNHS). The proposed methodology provides a promising candidate for efficient drug development in DMD and other rare diseases.
