The Biomarkers Consortium: On the Critical Path of Drug Discovery

Recent advances in science have provided a variety of genetic, genomic, and protein-based methods to treat human diseases.1,2 These advances, and equally great strides in in vivo imaging3,4,5,6,7 and methods of tissue collection, have created an unprecedented opportunity to discover and develop biological markers of human disease. A biomarker is defined8,9 as a molecular, biological, or physical characteristic that indicates a specific physiologic state (see 1 for definitions). It is used in clinical practice to identify risk for disease, diagnose disease and its severity, guide intervention strategies, and monitor patient responses to therapy. When used in a clinical research setting, biomarkers may predict whether a drug or other intervention is safe and effective10 in a shorter time and at lower cost than clinical outcomes studies. For these and other reasons, including the ability to stratify patient groups based on objective criteria, biomarkers help promote regulatory approval of new therapeutic entities by pharmaceutical, biological, and device development teams. Clinical Pharmacology & Therapeutics (2008) doi:10.1038/sj.clpt.6100471 Table 1. Terms and their definitions commonly used in biomarker research and development Term Definition based on the Biomarkers Definitions Working Group (ref. 9) Accelerated approval rule The 1992 Food and Drug Administration policy states that certain drugs have been provisionally approved for clinical use based on their effectiveness on one or more surrogate endpoints Biomarker A characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic response to therapeutic intervention Clinical endpoint A characteristic or variable that describes how a patient feels, functions, or survives Qualification The process of linking a biomarker to a clinical endpoint Stratification Process by which individuals in a clinical trial are placed into experimental groups based upon disease or a statistically defined predisposition to responding to therapy or experiencing particular toxicities Surrogate endpoint A subset of biomarkers that are intended to substitute for a clinical endpoint in therapeutic intervention trials, or in patient history or epidemiological studies. It is expected to predict clinical benefit or harm, or the lack of either Validation The process of linking a clinical endpoint to a surrogate endpoint