Hirakawa Akihiro, Wages Nolan A, Sato Hiroyuki, Matsui Shigeyuki
Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Department of Public Health Sciences, University of Virginia, Charlottesville, 22904, Virginia, U.S.A.
Stat Med. 2015 Oct 30;34(24):3194-213. doi: 10.1002/sim.6533. Epub 2015 May 13.
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.
对于联合I期试验中基于模型的竞争性剂量探索方法的相对性能，人们了解甚少。在本研究中，我们重点关注了最近开发的五种基于模型的剂量探索方法。我们比较了在3×3、4×4、2×4和3×5剂量组合矩阵的16种情况下，这些方法对真正的最大耐受剂量组合（MTDC）和过量组合的推荐率。我们发现，基于模型的剂量探索方法的性能因以下因素而异：（1）剂量组合矩阵是否为方形；（2）真正的MTDC是否沿剂量组合矩阵的对角线存在于同一组内；（3）真正的MTDC的数量。我们讨论了所比较的五种方法的操作特征细节以及优缺点。
