27: The Mystery of Clinical Trial Simulation

Dr. Scott Berry hosts this episode of "In the Interim…", opening with statistical analysis of elite athletes before focusing on the misunderstood role of clinical trial simulation. He distinguishes simulation as a predictive tool from its use as an in-silico process that enables trial design exploration, iteration, and optimization. Clinical trial simulation provides a mechanism for iterative comparison of multiple designs, driven by ongoing team feedback and evolving trial objectives. Scott stresses that rigid simulation plans are “not productive,” since the most effective designs typically emerge when stakeholders view real trial examples and suggest new design options in real time. The ICECAP trial serves as a key illustration, where the final design was shaped by simulation-informed team input across multiple iterations, from three tested durations to ten with response adaptive randomization. Scott also discusses the creation of the FACTS software, highlighting its ability to test alternative designs rapidly, present side-by-side comparisons, and conduct counterfactual analyses—revealing what different trial configurations would have produced using the same simulated datasets.

Key Highlights:

● Simulation contrasted as a predictive tool versus engine for iterative design evaluation.

● Emphasizes design process as team-driven and iterative, not prescriptive.

● Use of concrete example trials enhances communication across multidisciplinary teams.

● FACTS software enables design flexibility, in silico iteration, and comparative scenario analysis.

● ICECAP trial as an instance of simulation-informed design adaptation.