title: Statistical consideration and challenges in bridging study of personalized medicine.
abstract: 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 (e.g. overall survival) from CTA to CDx and to evaluate the drug efficacy in CDx intended use population. In this article, we will discuss statistical challenges in study design and data analysis for bridging study. Particularly, we aimed to provide 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.
authors.affiliation: a Division of Biostatistics, Center for Devices and Radiological Health , U.S. Food and Drug Administration , Silver Spring , Maryland , USA.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Li
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D019937:Diagnostic Techniques and Procedures / Q000706:statistics & numerical data; D004358:Drug Therapy / Q000706:statistics & numerical data; D006801:Humans; D057285:Precision Medicine / Q000379:methods / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015415:Biomarkers
keywords: Bridging study; Clinical trial assay; Companion diagnostic assay; Device-drug pivotal clinical trial; Device’s intended use population; Drug efficacy; Personalized medicine