Open Access
June 2011 Bayesian phase I/II adaptively randomized oncology trials with combined drugs
Ying Yuan, Guosheng Yin
Ann. Appl. Stat. 5(2A): 924-942 (June 2011). DOI: 10.1214/10-AOAS433


We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding in phase I. After identifying a set of admissible doses, we immediately move the entire set forward to phase II. We propose a novel adaptive randomization scheme to favor assigning patients to more efficacious dose-combination arms. Our adaptive randomization scheme takes into account both the point estimate and variability of efficacy. By using a moving reference to compare the relative efficacy among treatment arms, our method achieves a high resolution to distinguish different arms. We also consider groupwise adaptive randomization when efficacy is late-onset. We conduct extensive simulation studies to examine the operating characteristics of the proposed design, and illustrate our method using a phase I/II melanoma clinical trial.


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Ying Yuan. Guosheng Yin. "Bayesian phase I/II adaptively randomized oncology trials with combined drugs." Ann. Appl. Stat. 5 (2A) 924 - 942, June 2011.


Published: June 2011
First available in Project Euclid: 13 July 2011

zbMATH: 1232.62155
MathSciNet: MR2840181
Digital Object Identifier: 10.1214/10-AOAS433

Keywords: Adaptive randomization , dose finding , drug combination

Rights: Copyright © 2011 Institute of Mathematical Statistics

Vol.5 • No. 2A • June 2011
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