Statistical Evaluation of the Analytic Performance of a Clinical Sequencing Assay

• Activity Number: 693
• Type: Contributed
• Date/Time: Thursday, August 13, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Section on Medical Devices and Diagnostics
• Author(s): Eric Polley* and Lun-Ching Chang
• Companies: National Cancer Institute and National Cancer Institute
• Keywords: Study Design ; Biomarker ; Next Generation Sequencing ; Precision Medicine

Abstract

Cancer is caused by mutations in somatic cells, and the effects of the somatic aberrations can be used as drug targets. Given the growing list of known aberrations, many precision medicine clinical trials are moving to high throughput sequencing assays that test possibly thousands of biomarkers with a single sample. The multi-analyte design of these sequencing assays provide challenges in evaluating the analytic performance of the assay. In most cases the number of possible sequence aberrations is unknown or too large to quantify and it would be impossible to test samples with all known positive biomarkers that could be detected by the assay. We propose a framework for performance metrics that can be estimated with a sequencing assay and describe the study designs necessary to estimate the proposed metrics. This talk will include examples from developing targeted amplicon sequencing assays to be used for treatment selection as part of the National Cancer Institute precision medicine clinical trials initiatives.