The Challenges of Validating in Precision Medicine: The Case of Excision Repair Cross-Complement Group 1 Diagnostic Testing

Abstract

Abstract Personalized medicine relies upon the successful identification and translation of predictive biomarkers. Unfortunately, biomarker development has often fallen short of expectations. To better understand the obstacles to successful biomarker development, we systematically mapped research activities for a biomarker that has been in development for at least 12 years: excision repair cross-complement group 1 protein (ERCC1) as a biomarker for predicting clinical benefit with platinum-based chemotherapy in non-small cell lung cancer. We found that although research activities explored a wide range of approaches to ERCC1 testing, there was little replication or validation of techniques, and design and reporting of results were generally poor. Our analysis points to problems with coordinating and standardizing research in biomarker development. Clinically meaningful progress in personalized medicine will require concerted efforts to address these problems. In the interim, health care providers should be aware of the complexity involved in biomarker development, cautious about their near-term clinical value, and conscious of applying only validated diagnostics in the clinic.