Ivanova Anastasia, Xiao Changfu
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Pharm Stat. 2013 Sep-Oct;12(5):309-14. doi: 10.1002/pst.1585. Epub 2013 Jul 26.
Consider the problem of estimating a dose with a certain response rate. Many multistage dose-finding designs for this problem were originally developed for oncology studies where the mean dose-response is strictly increasing in dose. In non-oncology phase II dose-finding studies, the dose-response curve often plateaus in the range of interest, and there are several doses with the mean response equal to the target. In this case, it is usually of interest to find the lowest of these doses because higher doses might have higher adverse event rates. It is often desirable to compare the response rate at the estimated target dose with a placebo and/or active control. We investigate which of the several known dose-finding methods developed for oncology phase I trials is the most suitable when the dose-response curve plateaus. Some of the designs tend to spread the allocation among the doses on the plateau. Others, such as the continual reassessment method and the t-statistic design, concentrate allocation at one of the doses with the t-statistic design selecting the lowest dose on the plateau more frequently.
考虑估计具有特定反应率的剂量这一问题。针对此问题的许多多阶段剂量探索设计最初是为肿瘤学研究开发的，在肿瘤学研究中，平均剂量反应随剂量严格增加。在非肿瘤学II期剂量探索研究中，剂量反应曲线在感兴趣的范围内通常会趋于平稳，并且有几个剂量的平均反应等于目标值。在这种情况下，通常希望找到这些剂量中最低的那个，因为更高的剂量可能具有更高的不良事件发生率。通常需要将估计的目标剂量下的反应率与安慰剂和/或活性对照进行比较。我们研究了为肿瘤学I期试验开发的几种已知剂量探索方法中，哪一种在剂量反应曲线趋于平稳时最为合适。一些设计倾向于将分配分散在平稳期的各个剂量之间。其他设计，如连续重新评估法和t统计量设计，则将分配集中在其中一个剂量上，t统计量设计更频繁地选择平稳期的最低剂量。
