Strategic approach to fit-for-purpose biomarkers in drug development.

The strategic, fit-for-purpose use of the combination of robust target engagement and well-qualified disease-related biomarkers enhances understanding of the mechanism of action, ties together preclinical and clinical data, enables the assessment of target engagement, facilitates early proof of concept and dose focusing, and increases the efficiency of early clinical development with improved quality of decision making. Significant progress in biomarker discovery, validation, and qualification has increased drug-development decision making and regulatory applications. Target engagement biomarkers are present early in a pathophysiologic cascade and inform on physical or biological interactions with the molecular target of the drug. Disease-related biomarkers are present late in the pathophysiologic cascade and are linked to clinical benefit; thus, they assess a drug's effect on a particular disease. Together, these concepts lay the groundwork for high-quality drug-development decision making and a framework for the acceptance and qualification of biomarkers for regulatory use.