The Impact of an Inaccurate Diagnostic Biomarker on Phase II Clinical Trials in The Development of Targeted Therapy.
Current research in oncology aims at developing targeted therapies to treat the heterogeneous patient population. Successful development of a targeted therapy requires a biomarker that identifies patients who are most likely to benefit from the treatment. However, most biomarkers are inherently inaccurate. We present a simulation study to examine how the sensitivity and specificity of a single, binary biomarker influences the Cox estimates of hazard ratios in phase II clinical trials. We discuss how the bias introduced by marker inaccuracy impacts the decision of whether to carry a drug forward to a phase III clinical trial. Finally, we propose a bootstrap-based method for reducing the bias of the Cox estimator, in the presence of an inaccurate marker.