Assessment of treatment effect heterogeneity for multiregional randomized clinical trials.

Multiregional clinical trials (MRCTs) have become increasingly common in recent years. Detecting underlying regional heterogeneity is a critical issue for these trials. Existing methods for assessing treatment effect heterogeneity across regions have ignored the incomparability of baseline extrinsic risk factors of the randomized patients from different regions. In this paper, a calibration weighting method is proposed to calibrate the distribution of these extrinsic risk factors between multiple regions. We establish the consistency and the asymptotic normality of the calibration weighting estimator. Simulation studies confirm the finite sample properties of the proposed estimator as well as its superior performance over naive methods and the inverse probability weighting method. The proposed method is illustrated using a randomized clinical trial of adjuvant chemotherapy for resected non-small-cell lung cancer.

Duke Scholars

Author Stephen L. George Biostatistics & Bioinformatics, Division of Biostatistics

Author Xiaofei Wang Biostatistics & Bioinformatics, Division of Biostatistics