Boosting the Power of Hybrid Design When Crossover Occurred in Historical Control

Music City Center 

The hybrid design of augmenting concurrent control by borrowing historical control offers a promising solution when enrolling control patients is challengeable. It not only ensures the desired trial efficiency but also maintains the randomization property of clinical trials. In this design, population heterogeneity between historical and concurrent controls limits the data that can be borrowed, thereby hindering trial efficiency. Many studies addressed this issue focusing on two sources of heterogeneity: differences in patients' characteristics, and population drift caused by evolving SOC. However, when overall survival is the endpoint in oncology trials, crossover occurred in historical control result in additional discrepancies between historical and concurrent controls. Existing methods are deficient to fully resolve this issue.
Our study proposed a new design by integrating the adjustment of crossover effect into a hybrid framework of Bayesian dynamic borrowing model. We conducted extensive simulations to evaluate the performances under various scenarios, demonstrating the effectiveness of this framework in reducing estimate bias and boosting the power of hybrid design.

Hybrid design

RCT

Historical control

Crossover

Bayesian dynamic borrowing

Commensurate prior 

Biopharmaceutical Section