Biomarkers and Sustainable Innovation in Cardiovascular Drug Development:
Lessons from Near and Far Afield
Russell M. Medford, MD, PhD*, T. Forcht Dagi, MD, Robert S. Rosenson, MD and Margaret K. Offermann MD, PhD
From the abstract: Future innovative therapies targeting cardiovascular disease (CVD) have the potential to improve health outcomes and to contain rising healthcare costs. Unsustainable increases in the size, cost and duration of clinical trial programs necessary for regulatory approval, however, threaten the entire innovation enterprise. Rising costs for clinical trials are due in large part to increasing demands for hard cardiovascular clinical endpoints as measures of therapeutic efficacy. The development and validation of predictive and surrogate biomarkers, as laboratory or other objective measures predictive or reflective of clinical endpoints, are an important part of the solution to this challenge. This review will discuss insights applicable to CVD derived from the use of predictive biomarkers in oncologic drug development, the evolving role of high density lipoprotein (HDL) in CVD drug development and the impact biomarkers and surrogates have on the continued investment from multiple societal sources critical for innovative CVD drug discovery and development.
From the conclusion: ... the use of surrogates in phased clinical drug development through Phase II is based on the calculus that the value of surrogate endpoints on the whole outweighs the risks that the surrogate may not reflect ultimate hard clinical outcomes. The challenge in the cardiovascular arena is to improve and validate the library of available markers such that the same risk/benefit calculus can be applied across the entire drug development process through to regulatory approval. The lack of adequate surrogates and predictive biomarkers, and with them, the lack of new, clinically available and innovative therapeutic approaches to cardiovascular disease, is the social cost to be paid for a reluctance to integrate emerging scientific information into the methodology and standards for drug development.