P15 IRT Implementation Considerations for Bayesian Response-Adaptive Randomization in Platform Trials

Platform Trials are a classification of Master Protocols, which are perpetual and allow for planned treatment adaptations to occur across the trial's duration. These adaptations include introducing new treatments; opening, closing, pausing, re-opening existing treatments; and applying allocation ratio adjustments. Platform Trials often include multiple subgroups (e.g., sub-protocols, sub-studies, sub-populations) with independent randomization schemes with unique treatment inclusion / exclusion and ratio weights applied.

Due to the randomization's complexity in Platform Trials, an Interactive Response Technology (IRT, also known as Randomization and Trial Management) System is utilized. There are several considerations to account for regarding the Platform Trial IRT's randomization implementation to ensure efficient adaptions. These considerations involve how to manage adaptations for existing treatments, perform allocation ratio adjustments, add new treatments, configure an adaptable randomization scheme, and handle subgroup / site / subject eligibility.

Bayesian Response-Adaptive Randomization (BRAR) is a type of randomization that may be used within Platform Trials. BRAR is a probabilistic randomization methodology where treatment assignment probabilities are updated continuously based on accumulating subject response data. In addition to IRT considerations specific to Platform Trials, there are considerations unique to BRAR. These include the approach to updating treatment assignment probabilities (e.g., user-entered interface or data integration of BRAR algorithm), structure of random numbers used for treatment assignment (e.g., unrestricted, restricted), and handling of eligibility. This poster will describe the IRT implementation considerations for Platform Trials with BRAR, include examples of approaches, and provide guidance for making decisions for the IRT's design.

Clinical Trial Design (e.g., Innovative/Complex Design, Estimands, Master Protocol)

ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2024