A PRIM approach to predictive‐signature development for patient stratification |
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Authors: | Gong Chen Hua Zhong Anton Belousov Viswanath Devanarayan |
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Affiliation: | 1. Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center New York, Roche TCRC, Inc., New York, U.S.A.;2. Population Health, Division of Biostatistics, NYU School of Medicine, New York, U.S.A.;3. Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Penzberg, Germany;4. AbbVie, Inc., North Chicago, U.S.A. |
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Abstract: | Patients often respond differently to a treatment because of individual heterogeneity. Failures of clinical trials can be substantially reduced if, prior to an investigational treatment, patients are stratified into responders and nonresponders based on biological or demographic characteristics. These characteristics are captured by a predictive signature. In this paper, we propose a procedure to search for predictive signatures based on the approach of patient rule induction method. Specifically, we discuss selection of a proper objective function for the search, present its algorithm, and describe a resampling scheme that can enhance search performance. Through simulations, we characterize conditions under which the procedure works well. To demonstrate practical uses of the procedure, we apply it to two real‐world data sets. We also compare the results with those obtained from a recent regression‐based approach, Adaptive Index Models, and discuss their respective advantages. In this study, we focus on oncology applications with survival responses. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. |
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Keywords: | biomarker patient rule induction method (PRIM) patient stratification predictive signature subgroup analysis |
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