title: A default method to specify skeletons for Bayesian model averaging continual reassessment method for phase I clinical trials.
abstract: The Bayesian model averaging continual reassessment method (CRM) is a Bayesian dose-finding design. It improves the robustness and overall performance of the continual reassessment method (CRM) by specifying multiple skeletons (or models) and then using Bayesian model averaging to automatically favor the best-fitting model for better decision making. Specifying multiple skeletons, however, can be challenging for practitioners. In this paper, we propose a default way to specify skeletons for the Bayesian model averaging CRM. We show that skeletons that appear rather different may actually lead to equivalent models. Motivated by this, we define a nonequivalence measure to index the difference among skeletons. Using this measure, we extend the model calibration method of Lee and Cheung (2009) to choose the optimal skeletons that maximize the average percentage of correct selection of the maximum tolerated dose and ensure sufficient nonequivalence among the skeletons. Our simulation study shows that the proposed method has desirable operating characteristics. We provide software to implement the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biostatistics, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, 77030, TX, U.S.A.|School of Statistics, Xi'an University of Finance and Economics, Xi'an, 710061, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Biostatistics, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, 77030, TX, U.S.A.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D001499:Bayes Theorem; D056808:Biostatistics; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020714:Maximum Tolerated Dose; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy; D013810:Therapeutic Equivalency
chemical_list: D000970:Antineoplastic Agents
keywords: BMA-CRM; Bayesian adaptive design; continual reassessment method; maximum tolerated dose; skeleton specification