Enhancing generalizability and efficiency in clinical trials through dynamic information borrowing for both experimental and control arms: A simulation study.

Abstract

Aim: Utilizing external information in clinical trials enhances validity by including a wider population and expedites the implementation of adaptive designs, ultimately improving research efficiency. However, current research focused on scenarios in which only the control group benefited from the utilization of external information, while trials involving external information in both experimental and control arms were more complex and might pose challenges when applied in real-world settings.

Methods: To address these concerns, our study pioneered the application of test-then-pool, normalized power prior, calibrated power prior, and elastic prior to a two-arm information borrowing framework and systematically compared their operating characteristics through a series of simulation studies under most and least desirable scenarios.

Results: In the most desirable scenarios of information borrowing, all methods managed to control the mean of type I error rates within 5%, among which the normalized power prior, calibrated power prior and elastic prior approaches increased the mean of power from 85.94% to 95%. In the least desirable scenarios, the mean type I error rates for normalized power prior, calibrated power prior and elastic prior approaches exceeded 20%, while the mean power decreased to around 80%.

Conclusions: Our findings reveal that the normalized power prior, calibrated power prior and elastic prior approaches are suitable for situations with minimal heterogeneity between historical and current data, whereas the test-then-pool approach emerges as a more prudent choice when facing substantial discrepancies between historical and current information for trials consider information borrow in both arms.