A comparative study of adaptive dose-finding designs for phase I oncology trials of combination therapies.
A comparative study of adaptive dose-finding designs for phase I oncology trials of combination therapies.
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DOI：
10.1002/sim.6533
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发表时间：
2015-10-30
影响因子：
2
通讯作者：
Matsui S
中科院分区：
文献类型：
--
作者：
Hirakawa A;Wages NA;Sato H;Matsui S
对于组合 I 期试验中基于模型的竞争剂量寻找方法的相对性能知之甚少。在这项研究中，我们重点关注最近开发的五种基于模型的剂量寻找方法。我们比较了 3 × 3、4 × 4、2 × 4 和 3 × 5 剂量组合矩阵在 16 种情况下这些方法的真实最大耐受剂量组合 (MTDC) 和过量剂量组合的推荐率。我们发现基于模型的剂量寻找方法的性能取决于（1）剂量组合矩阵是否为方阵； (2)沿剂量组合矩阵对角线的同一组内是否存在真正的MTDC； (3) 真实 MTDC 的数量。我们详细讨论了五种方法的操作特点以及优缺点的比较。
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.