A visualization method measuring the performance of biomarkers for guiding treatment decisions

摘要

Biomarkers that predict efficacy and safety for a given drug therapy become increasingly important for treatment strategy and drug evaluation in personalized medicine. Methodology for appropriately identifying and validating such biomarkers is critically needed, although it is very challenging to develop, especially in trials of terminal diseases with survival endpoints. The marker-by-treatment predictiveness curve serves this need by visualizing the treatment effect on survival as a function of biomarker for each treatment. In this article, we propose the weighted predictiveness curve (WPC). Based on the nature of the data, it generates predictiveness curves by utilizing either parametric or nonparametric approaches. Especially for nonparametric predictiveness curves, by incorporating local assessment techniques, it requires minimum model assumptions and provides great flexibility to visualize the marker-by-treatment relationship. WPC can be used to compare biomarkers and identify the one with the highest potential impact. Equally important, by simultaneously viewing several treatment-specific predictiveness curves across the biomarker range, WPC can also guide the biomarker-based treatment regimens. Simulations representing various scenarios are employed to evaluate the performance of WPC. Application on a well-known liver cirrhosis trial sheds new light on the data and leads to discovery of novel patterns of treatment biomarker interactions. Copyright (c) 2015 John Wiley & Sons, Ltd.