09/26/2025: 8:30 AM EDT - 9:45 AM EDT
Parallel
Room: Brookside C
Incorporating external data into clinical trial designs has become an increasingly important strategy for improving efficiency and feasibility of modern clinical research. Leveraging information from historical trials or real-world evidence may reduce the number of participants required for new studies, improve precision of treatment effect estimates, and address recruitment challenges that make research in rare diseases impractical. However, to meet the regulatory requirements for approval and maintain the rigorous standards that make RCTs the "gold standard" of clinical research, it is vital that trial designers utilize statistical approaches that mitigate the potential biases that arise due to differences between external and current datasets.
With the increased utilization of these designs, we now have examples of trials that have been designed, reviewed by regulatory agencies, conducted and completed, and resulted in regulatory approval. We propose a session to review two case studies of completed trials leading to approval, with an assessment of the benefits of the statistical borrowing and lessons learned for future trials.
This session will feature three presentations focusing on applications of statistical borrowing in clinical trials that led to successful regulatory approval. The first two talks will showcase two real trials with a focus on the statistical borrowing approaches utilized, the interactions with FDA, and the impact of borrowing on the trial outcomes. The session will conclude with a presentation by an FDA representative who will provide a regulatory perspective on the two highlighted trials.
borrowing
case studies
Organizer
Lindsay Berry, Berry Consultants
Chair
Lindsay Berry, Berry Consultants
Topic Description
Clinical Trial Design (Innovative/complex design, Master Protocol, multiplicity, multi-regional clinical trial, etc.)
ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2025
Presentations
This talk presents a second case study of statistical borrowing in a regulatory setting, focusing on the statistical approach to borrowing, regulatory interactions, and the impact of borrowing on the final trial results.
Presenting Author
Inna Perevozskaya, BMS
In this presentation, I will discuss the regulatory perspectives on two recent approvals that were supported primarily by Bayesian analyses. Additionally, I will highlight some key points from the upcoming draft FDA guidance "Use of Bayesian Methodology in Clinical Trials of Drug and Biological Products."
Presenting Author
Lihan Yan, FDA
The PUNCH CD3 study was a randomized, double-blind, placebo controlled, phase III trial to study the effect of RBX 2660 in patients with recurrent Clostridioides difficile infection. A distinctive aspect of the study design is the primary analysis, which used a unique Bayesian borrowing approach that incorporated efficacy data from a previous phase II study of RBX2600. While the borrowing of external data is relatively common in some settings, it's use in a registrational study is unusual due to statistical concerns such as type I error inflation or bias.
This talk discusses the underlying rationale for borrowing in this trial, providing insight into the scientific and clinical considerations that addressed these statistical concerns. We then discuss the design process used to develop the primary analysis, addressing key aspects of borrowing methodology such as the assumption of exchangeability and the specification of Bayesian priors. The primary analysis used a dynamic borrowing strategy, and we show how this results in an improvement in the operating characteristics relative to non-dynamic borrowing. The results of the study demonstrate the value of dynamic borrowing in action and provide an example where the joint analysis of Phase II and Phase III data led to a positive conclusion and ultimately FDA approval.
Presenting Author
Anna McGlothlin, Berry Consultants