A comparative study of adaptive dose‐finding designs for phase I oncology trials of combination therapies |
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| Authors: | Akihiro Hirakawa Nolan A. Wages Hiroyuki Sato Shigeyuki Matsui |
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| Affiliation: | 1. Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan;2. Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, U.S.A.;3. Biostatistics Group, Office of New Drug V, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan;4. Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan |
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| 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. Copyright © 2015 John Wiley & Sons, Ltd. |
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| Keywords: | combination of two agents comparative study dose‐finding method phase I trial oncology |
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