title: Dose-finding based on bivariate efficacy-toxicity outcome using Archimedean Copula.
abstract: In dose-finding clinical study, it is common that multiple endpoints are of interest. For instance, efficacy and toxicity endpoints are both primary in clinical trials. In this article, we propose a joint model for correlated efficacy-toxicity outcome constructed with Archimedean Copula, and extend the continual reassessment method (CRM) to a bivariate trial design in which the optimal dose for phase III is based on both efficacy and toxicity. Specially, considering numerous cases that continuous and discrete outcomes are observed in drug study, we will extend our joint model to mixed correlated outcomes. We demonstrate through simulations that our algorithm based on Archimedean Copula model has excellent operating characteristics.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China ; Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China ; Department of Mathematics, China Pharmaceutical University, Nanjing, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Tao
authors.forename: Junlin
authors.initials: J
authors.lastname: Liu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Li
authors.forename: Jinguan
authors.initials: J
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.forename: Fangrong
authors.initials: F
authors.lastname: Yan
mesh_terms: D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015233:Models, Statistical; D000069437:Pharmacological Phenomena; D018675:Toxicity Tests
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors