Atherosclerosis drug development in jeopardy: the need for predictive biomarkers of treatment response.

The limited predictability of phase II biomarkers for atherosclerosis outcomes in phase III studies stands in contrast to the number and varied types of biomarkers--soluble, imaging, and functional--that have been used in a diverse array of trials. Although collectively abundant, these biomarker data exist in a fragmented state. Most biomarkers are studied one at a time, only measure a specific aspect of atherosclerosis, are not integrated in a substantive way, and compete with one another for validation; in the end, progress is slow. The proposed solution from the Atherosclerosis Working Group, a committee of experts from academia, the pharmaceutical industry, government, and the nonprofit sector and managed by the Foundation for the National Institutes of Health Biomarkers Consortium, is to integrate these different measures into an in silico model of atherosclerosis. Through integration of diverse biomarker measurements and outcomes in silico, we may be able to improve trial design as well as the predictive power of short-term markers for longer-term outcomes.