Wages Nolan A
Translational Research and Applied Statistics, Public Health Sciences, University of Virginia, Charlottesville, 22908, VA, U.S.A.
Stat Med. 2017 Jan 30;36(2):242-253. doi: 10.1002/sim.6918. Epub 2016 Feb 22.
The majority of phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDCs for further testing for efficacy in a phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDCs. Operating characteristics are demonstrated through simulation studies and are compared with existing methodology. Some brief discussion of implementation and available software is also provided. Copyright © 2016 John Wiley & Sons, Ltd.
多药物试验的大多数I期方法都集中在在所研究的剂量组合中确定单一的最大耐受剂量组合（MTDC）。该领域已发表的一些方法基于这样的观念，即不存在唯一的MTDC，并且具有可接受毒性的剂量组合集在二维空间中形成一个等效轮廓。因此，在II期试验中寻找多个MTDC以进一步测试疗效可能是有意义的。在本文中，我们提出了一种新的剂量寻找方法，该方法扩展了连续重新评估方法以考虑多个MTDC的位置。通过模拟研究展示了操作特征，并与现有方法进行了比较。还提供了关于实施和可用软件的一些简要讨论。版权所有© 2016约翰威立父子有限公司。
