Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Aichi, 466-8560, Japan.
Stat Med. 2013 Nov 20;32(26):4515-25. doi: 10.1002/sim.5843. Epub 2013 May 6.
We develop a novel dose-finding method for two-agent combination phase I trials on the basis of the shrunken predictive probability of toxicity. In this method, a shrinkage logistic regression model that allows distinct shrinkage multipliers for the coefficients of the main effects of two agents and their interaction on the probability of toxicity constructs the toxicity outcome. We also propose dose-escalation/de-escalation decision rules on the basis of the shrunken predictive probability of toxicity. Simulation studies under various patterns of monotonic dose-response relationships for combinations of two agents demonstrated that the proposed method performed no worse than the existing two dose-finding methods we selected.
我们基于毒性缩小预测概率开发了一种新的两药联合Ⅰ期试验剂量探索方法。在这种方法中，构建毒性结果的是一个允许两个药物的主效应及其相互作用的系数有不同收缩倍数的收缩逻辑回归模型。我们还基于毒性缩小预测概率提出了剂量递增/递减决策规则。在两个药物组合的各种单调剂量反应模式下的模拟研究表明，所提出的方法并不逊于我们选择的两种现有的剂量探索方法。
