title: A comparative study of adaptive dose-finding designs for phase I oncology trials of combination therapies.
abstract: Little is known about the relative performance of competing model-based dose-finding methods for combination phase I trials. In this study, we focused on five model-based dose-finding methods that have been recently developed. We compared the recommendation rates for true maximum-tolerated dose combinations (MTDCs) and over-dose combinations among these methods under 16 scenarios for 3 × 3, 4 × 4, 2 × 4, and 3 × 5 dose combination matrices. We found that performance of the model-based dose-finding methods varied depending on (1) whether the dose combination matrix is square or not; (2) whether the true MTDCs exist within the same group along the diagonals of the dose combination matrix; and (3) the number of true MTDCs. We discuss the details of the operating characteristics and the advantages and disadvantages of the five methods compared.
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirakawa
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, 22904, Virginia, U.S.A.
authors.forename: Nolan A
authors.initials: NA
authors.lastname: Wages
authors.affiliation: Biostatistics Group, Office of New Drug V, Pharmaceuticals and Medical Devices Agency, Tokyo, 100-0013, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Matsui
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001499:Bayes Theorem; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D003198:Computer Simulation; D006801:Humans; D016013:Likelihood Functions; D016015:Logistic Models; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy*
keywords: combination of two agents; comparative study; dose-finding method; oncology; phase I trial