SOME PRACTICAL IMPROVEMENTS IN THE CONTINUAL REASSESSMENT METHOD FOR PHASE-I STUDIES
SOME PRACTICAL IMPROVEMENTS IN THE CONTINUAL REASSESSMENT METHOD FOR PHASE-I STUDIES
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DOI：
10.1002/sim.4780141102
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发表时间：
1995-06-15
影响因子：
2
通讯作者：
PIANTADOSI, S
中科院分区：
文献类型：
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作者：
GOODMAN, SN;ZAHURAK, ML;PIANTADOSI, S
连续再评估方法(CRM)是一种贝叶斯第一阶段设计，其目的是估计一种药物的最大耐受量，该药物将用于随后的第二阶段和第三阶段研究。与标准方法相比，CRM设计的持续时间更长，以及对高剂量水平的过度试验以及更频繁和更严重的毒性的担忧，阻碍了它的接受。本文介绍了一项模拟研究的结果，在该模拟研究中，一个人一次为每个剂量水平分配多个受试者，并且每次剂量增加被限制在一个水平。我们表明，这些修改解决了所有对CRM最严重的批评，将试验持续时间缩短了50%-67%，将毒性发生率降低了20%-35%，并降低了毒性严重程度。这些都是在对精度影响最小的情况下实现的。最重要的是，根据我们在我们机构的经验，这样的修改使临床研究人员可以接受CRM。
The Continual Reassessment Method (CRM) is a Bayesian phase I design whose purpose is to estimate the maximum tolerated dose of a drug that will be used in subsequent phase II and III studies. Its acceptance has been hindered by the greater duration of CRM designs compared to standard methods, as well as by concerns with excessive experimentation at high dosage levels, and with more frequent and severe toxicity. This paper presents the results of a simulation study in which one assigns more than one subject at a time to each dose level, and each dose increase is limited to one level. We show that these modifications address ail of the most serious criticisms of the CRM, reducing the duration of the trial by 50-67 per cent, reducing toxicity incidence by 20-35 per cent, and lowering toxicity severity. These are achieved with minimal effects on accuracy. Most important, based on our experience at our institution, such modifications make the CRM acceptable to clinical investigators.