PS16: Advancing Rare Disease Drug Development: Leveraging External Controls and Novel Statistical Methods to Drive Regulatory Success

Rare disease drug development presents substantial challenges, particularly when patient populations are limited and concurrent control is not feasible. This session will examine the application of external controls and novel statistical approaches to address these challenges. The session will also discuss practical difficulties, share real-world experience, and explore potential advancements in the design and methods of clinical trials for rare diseases. The first presentation will discuss the application of external controls in Phase 3 trials for rare diseases. The speaker will discuss the scientific considerations for this approach and provide insights into how external controls can strengthen the design of robust clinical trials. The second presentation will focus on rank analysis for trials with small sample sizes, which is particularly useful in the context of clinical trials for rare and ultra-rare diseases. The speaker will demonstrate the statistical properties of the proposed method and illustrate its advantages. The session will conclude with remarks from a discussant from the FDA.