Affiliations: Biometric Research Branch, NIH, Bethesda, MD, USA | Biostatistics Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Correspondence:
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Corresponding author: Richard Simon, D.Sc., Biometric Research Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda MD 20892-7434, USA. Tel.: +1 301 496 0975; Fax: +1 301 402 0560; E-mail: rsimon@mail.nih.gov.
Abstract: Physicians need improved tools for selecting treatments for individual patients. Many syndromes traditionally viewed as individual diseases are heterogeneous in molecular pathogenesis and treatment responsiveness. This results in treatment of many patients with ineffective drugs and leads to the conduct of large clinical trials to identify small average treatment benefits for heterogeneous groups of patients. New genomic and proteomic technologies provide powerful tools for the selection of patients likely to benefit from a therapeutic without unacceptable adverse events. In spite of the large literature on developing predictive biomarkers and on statistical methodology for analysis of high dimensional data, there is considerable uncertainty about the validation of biomarker based diagnostic classifiers for treatment selection. In this paper we attempt to clarify these issues and to provide guidance on the design of clinical trials for evaluating the clinical utility and robustness of pharmacogenomic classifiers.
Keywords: Pharmacogenomics, biomarker, genomics, DNA microarray, clinical trial design, validation
