Statistical Methods for Bridging Studies of Companion Diagnostic Devices in Precision Medicine
*Meijuan Li, US Food and Drug Administration 


Applications of personalized medicine are becoming increasingly prominent. A well-characterized market-ready companion diagnostic assay (CDx) is often desired for patient enrollment in device-drug pivotal clinical trial(s) so that Food and Drug Administration can ensure that appropriate clinical and analytical validation studies are planned and carried out for CDx. However, such a requirement may be difficult or impractical to accomplish. A clinical trial assay (CTA) instead of CDx may be used for patient enrollment in the clinical trial. A concordance study (or bridging study) will be required to assess the agreement between CDx and CTA in order to bridge the clinical data from CTA to CDx and to evaluate the drug efficacy in CDx intended use population. In this paper, we will discuss statistical challenges in study design and data analysis for bridging study. Particularly, we aimed to provide new statistical methods on how to estimate the drug efficacy in CDx intended use population using results from bridging study and CTA-drug pivotal clinical trial.