In today's blog, Dr. Kert Viele breaks down the most crucial updates of the draft guidance on "Master Protocols for Drug and Biological Product Development," specifically focusing on the new details surrounding basket trials, control group requirements, and the heavy integration of the FDA's draft Bayesian guidance.

In this week's blog, Dr. Kert Viele discusses his thoughts on the RAR literature and the current state of RAR in practical clinical trials. He focuses on general principles that have emerged in the literature, the nuts and bolts of constructing and tuning RAR designs, and operational issues.

Longitudinal modeling and predictive modeling are the foundation of learning efficiently in adaptive clinical trials, allowing real-time learning from early data. Bayesian models enable faster, more informed decisions even when primary endpoints are distant.

REMAP-CAP, ATTACC, and ACTIV-4a unified under a multi-platform randomized clinical trial with a joint Bayesian adaptive design, rapidly determining that therapeutic anticoagulation benefits moderate, but not severe, COVID-19 patients.

ICH-E20’s regulatory caution towards adaptive designs is often misapplied, resulting in inefficient or unrealistic alternatives for sponsors and patients. Operational casework demonstrates that so-called “complexity” in adaptive design is frequently misunderstood and that regulatory “false choices” undermine trial effectiveness.

Bayesian borrowing in Phase 3 trials formally combines prior evidence with the new trial data to enhance development efficiency and regulatory decision making. This approach requires rigorous statistical modeling, careful selection of historical information, and detailed regulatory dialogue.