Robust and Data-Adaptive Integration of Nonconcurrent Data in Platform Trials via Gaussian Processes

Thomas M. Menino Convention & Exhibition Center 

A platform trial is an innovative clinical trial design that enables simultaneous and continuous evaluation of multiple treatments within a single master protocol. Existing robust methods restrict analyses to concurrently randomized participants due to concerns that including nonconcurrent data may introduce bias from temporal trends. However, this exclusion represents a missed opportunity to improve efficiency. We propose a Gaussian process framework for incorporating nonconcurrent data that exploits temporal smoothness, a key feature of platform trials. The framework includes single-task and multi-task formulations and provides data-adaptive integration of nonconcurrent data with uncertainty quantification. The connection to kernel ridge regression yields a transparent frequentist interpretation of how nonconcurrent data are integrated. We establish two theoretical guarantees: incorporating nonconcurrent controls reduces the posterior variance of the treatment effect, and the resulting bias is controlled by a non-increasing bound. We extend the framework to discrete outcomes and to covariate adjustment, illustrate it on a hypothetical platform trial constructed from SURMOUNT-1, and provide an implementation in the R package RobinCID.

Causal inference

Kernel ridge regression

Master protocol

Nonconcurrent controls

Temporal smoothness 

Biopharmaceutical Section