Guidelines for the Development and Incorporation of Biomarker Studies in Early Clinical Trials of Novel Agents

The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and Drug Administration (FDA) guidance docu- ments, and conducted a survey of investigators to determine practices and challenges to executing biomarker studies in clinical trials of new drugs in early development. This document provides stan- dard definitions and categories of biomarkers, and lists recommendations to sponsors and investiga- tors for biomarker incorporation into such trials. Our recommendations for sponsors focus on the identification and prioritization of biomarkers and assays, the coordination of activities for the devel- opment and use of assays, and for operational activities. We also provide recommendations for in- vestigators developing clinical trials with biomarker studies for scientific rationale, assay criteria, trial design, and analysis. The incorporation of biomarker studies into early drug trials is complex. Thus the decision to proceed with studies of biomarkers should be based on balancing the strength of science, assay robustness, feasibility, and resources with the burden of proper sample collection on the patient and potential impact of the results on drug development. The Task Force provides these guidelines in the hopes that improvements in biomarker studies will enhance the efficiency of inves- tigational drug development. Clin Cancer Res; 16(6); 1745-55. ©2010 AACR. In an era of increasing number of identified cancer tar- gets and agents affecting those targets, efforts to determine target modulation, and to find subpopulations of patients most likely to benefit or experience harm from therapy, are potentially valuable for rational prioritization of therapies for clinical research evaluation and for individual patient management. Although nearly half of the recently ap- proved oncology therapies have predictive markers, the qualification of putative biomarkers remains limited and the practical realization of successful biomarker use in ear- ly clinical drug development remains to be more fully de- veloped. A recent extensive review of the use of biomarker