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Activity Number: 408
Type: Contributed
Date/Time: Tuesday, July 31, 2012 : 2:00 PM to 3:50 PM
Sponsor: Section on Bayesian Statistical Science
Abstract - #305735
Title: Phase I Dose-Finding Designs for Optimal Biological Dose
Author(s): Yong Zang*+ and Jack Lee, Ph.D. and Ying Yuan
Companies: MD Anderson Cancer Center and MD Anderson Cancer Center and MD Anderson Cancer Center
Address: 1400 Pressler St, Houston, TX, 77030,
Keywords: phase I design ; dose finding ; Bayesian method ; logistic regression

Traditionally, the purpose of a phase I clinical trial design is to find the maximum tolerated dose (MTD) based solely on toxicity. However, for molecularly targeted agents, little toxicity may arise under the dose range considered. Furthermore, the dose-efficacy curves for molecularly targeted agents may not be monotonic, which poses a considerable challenge for dose finding.

In this talk, we propose three phase I dose-finding designs for trials evaluating molecularly targeted agents. The focus of these designs is finding the optimal biological dose (OBD) with the highest rate of efficacy. The first design fits the dose-efficacy curve using a Bayesian logistic regression. The second design is nonparametric in the sense that it locates the OBD using a dynamic double-sided isotonic regression. The third design, referred as the L-logistic design, implements the dose-finding procedure based on the posterior probability of the local slope using logistic regression. We carry out simulation studies to investigate the finite-sample operating characteristics of the proposed designs and recommend the L-logistic design in general settings.

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