Applications of 'decisionable' biomarkers in cardiovascular drug development.

Biomarkers are now increasingly employed in drug development for decision-making. New targets and candidate drugs should not only have drug-like properties (i.e., be 'drugable'), but the supporting biomarker platform should be 'decisionable'. For example, biomarkers for target engagement have supported the biologic plausibility for novel mechanisms and have aided in accelerated proof of concept. In many other circumstances, biomarkers have aided in the elucidation of mechanisms of action and disease progression. In this article, decisonable biomarker principles that aid in decision-making within the realm of early discovery through to clinical proof of concept are discussed. Case studies of applications of both target engagement and disease-related biomarkers are illustrated in the field of cardiovascular drug discovery and translational development. We propose that biomarkers, if prospectively implemented in an early development program, have the potential to accelerate drug development, facilitate the design of informative trials and dose selection for accelerated development, and establish an overall increase in probability of developmental success and efficiency.