Biomarkers and biomarker validation: a pathologist's guide to getting it right.

Biomarkers are central to the delivery of personalised/precision medicine and are increasingly used across all areas of medicine to improve diagnostic accuracy, determine prognosis and predict response to treatment. Biomarkers can be used to develop assays that are then further developed into diagnostic tests, or in vitro diagnostic devices, which require an exhaustive validation and approval process. Pathologists play a critical role in the ordering and interpretation of biomarker assays. However, the evolution of a new biomarker from discovery to clinical implementation is complex, subject to various levels of scientific, clinical and regulatory scrutiny, with an approval process that varies significantly between jurisdictions. Therefore, it is important that pathologists have a solid understanding of how biomarkers are developed, the process of biomarker validation, how new biomarkers are approved for clinical use and the potential issues around implementation of biomarker testing that may lead to inaccurate results. This paper aims to provide an overview of the process of biomarker development, approval and validation, and practical tips for anatomical pathologists involved in the testing of biomarkers in routine practice.