All Times EDT
Keywords: Companion diagnostic, bridging study, low prevalence, NPA
A companion diagnostic (CDx) provides information that is essential for the safe and effective use of a corresponding therapeutic product. When a clinical trial assay (CTA) other than the CDx is used to enroll patients into a clinical trial, a bridging study is commonly used to validate the clinical performance of CDx by retesting patient samples using CDx. The bridging study assesses the agreement between CTA and CDx and evaluates the clinical efficacy of CDx in the intended use population (e.g. marker positive population defined by CDx). For low prevalence biomarkers such as NTRK gene fusions, the bridging study design and analysis could have some challenges. The limited number of biomarker-positive patients and missing data may present challenges. The negative percent agreement (NPA) between CTA and CDx is especially important for low prevalence biomarkers in determining the feasibility and success of a bridging study which may introduce additional challenges. In this presentation, we will discuss statistical challenges in study design and data analysis of companion diagnostic bridging studies for low prevalence biomarkers and provide some recommendations/solutions.