• Weili He, Jun Liu, Bruce Binkowitz, and Hui Quan.
• Clinical Biostatistics, Merck Research Labs, Merck & Co., Inc., Rahway, NJ 07065, USA. weili_he@merck.com
• Stat Med. 2006 Jun 30; 25 (12): 2027-42.

AbstractThe primary aim of a phase I cancer clinical trial is to determine the maximum tolerated dose (MTD) of a new agent. The MTD is determined as the highest dose level of a potential therapeutic agent at which the patients have experienced an acceptable level of dose limiting toxicity. Although many other types of designs have been proposed in recent years, the traditional algorithm-based designs, especially the 3+3 designs, are still widely used due to their practical simplicity. Simulation studies have shown that the traditional algorithm-based designs cannot provide reasonable estimates of the MTD due to their intrinsic design limitations. In this paper, we propose a model-based approach in the estimation of the MTD following a traditional 3+3 design. Simulation results indicate that our model-based approach produces much less biased estimates of the MTD compared to the estimates obtained from the traditional 3+3 designs. Furthermore, our model-based approach can be easily extended to any traditional A+B design.Copyright (c) 2005 John Wiley & Sons, Ltd.

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