How-to guide on biomarkers: biomarker definitions, validation and applications with examples from cardiovascular disease.

A biomarker is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. Many commonly used tests in clinical practice can serve as biomarkers. The majority have been identified on the basis of insight or underlying physiology or biological mechanisms. With increasing knowledge and practical experience, some of these tests have evolved into a measurable end point in clinical research, applied as an indicator of change, for the better or worse. The traditional identification of biomarkers as an observational side product of clinical practice is increasingly turning into an industrialised process of biomarker discovery, supported by standardised paradigms of biomarker validation and translation from bench to bedside. The potential utility of biomarkers in clinical studies, investigating either new treatments or new strategies of clinical management, is capitalizing on recent advances in technology, from molecular sciences to powerful imaging, bearing the promise of expediting the discovery of new treatments. In the active search for new biomarkers, many potential candidates can be considered side by side, allowing many failures but a few great winners. Biomarker discovery is an ongoing process, with translation being tested de novo in every single study, providing us with the opportunity to revise our knowledge of the complex scheme of human physiology and pathophysiology. In predicting what Nature has set in place, advances in technology may be only the first step. This review provides an introduction to the field of biomarker discovery and translation. It deals with evolving nomenclature, basic principles of the validation process, and, drawing on examples in cardiovascular medicine, their significance for clinical application.