Biomarkers are critical to the rational development of medical
therapeutics, but significant
confusion persists regarding fundamental definitions and concepts involved in their use in research and clinical practice, particularly in the fields of
chronic disease and nutrition. Clarification of the definitions of different
biomarkers and a better understanding of their appropriate application could result in substantial benefits. This review examines
biomarker definitions recently established by the U.S. Food and Drug Administration and the National Institutes of Health as part of their joint
Biomarkers, EndpointS, and other Tools (BEST) resource. These definitions are placed in context of their respective uses in patient care, clinical research, or therapeutic development. We explore the distinctions between
biomarkers and clinical outcome assessments and discuss the specific definitions and applications of diagnostic, monitoring, pharmacodynamic/response, predictive, prognostic, safety, and susceptibility/risk
biomarkers. We also explore the implications of current
biomarker development trends, including complex composite
biomarkers and digital
biomarkers derived from sensors and mobile technologies. Finally, we discuss the challenges and potential benefits of
biomarker-driven predictive toxicology and systems pharmacology, the need to ensure quality and reproducibility of the science underlying
biomarker development, and the importance of fostering collaboration across the entire ecosystem of medical product development. Impact statement
Biomarkers are critical to the rational development of medical diagnostics and
therapeutics, but significant
confusion persists regarding fundamental definitions and concepts involved in their use in research and clinical practice. Clarification of the definitions of different
biomarker classes and a better understanding of their appropriate application could yield substantial benefits.
Biomarker definitions recently established in a joint FDA-NIH resource place different classes of
biomarkers in the context of their respective uses in patient care, clinical research, or therapeutic development. Complex composite
biomarkers and digital
biomarkers derived from sensors and mobile technologies, together with
biomarker-driven predictive toxicology and systems pharmacology, are reshaping development of diagnostic and therapeutic technologies. An approach to
biomarker development that prioritizes the quality and reproducibility of the science underlying
biomarker development and incorporates collaborative regulatory science involving multiple disciplines will lead to rational, evidence-based
biomarker development that keeps pace with scientific and clinical need.