title: A design for phase I trials in completely or partially ordered groups.
abstract: We propose a design for dose finding for cytotoxic agents in completely or partially ordered groups of patients. By completely ordered groups, we mean that prior to the study, there is clinical information that would indicate that for a given dose, the groups can be ordered with respect to the probability of toxicity at that dose. With partially ordered groups, at a given dose, only some of the groups can be ordered with respect to the probability of toxicity at that dose. The method we propose includes elements of the parametric model used in the continual reassessment method combined with the Hwang-Peddada order-restricted estimation procedure. We evaluate the operating characteristics of these designs in a family of dose-toxicity curves representing complete and partial orders. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Public Health Sciences, University of Virginia Health System, P.O. Box 800717, Charlottesville, 22908, VA, U.S.A.
authors.forename: Mark R
authors.identifier: 0000-0002-0459-2336
authors.initials: MR
authors.lastname: Conaway
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D056808:Biostatistics; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data*; D003603:Cytotoxins / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D020714:Maximum Tolerated Dose; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D000099148:UGT1A1 Enzyme
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: cytotoxic agent; dose finding; heterogeneous groups