Garrett-Mayer Elizabeth
Division of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD, USA.
Clin Trials. 2006;3(1):57-71. doi: 10.1191/1740774506cn134oa.
The Continual Reassessment Method (CRM), along with other adaptive dose-finding study designs, has gained popularity since its proposal by O'Quigley. Several of the reasons it has been embraced by clinical trialists is that it tends to incur fewer toxic events, and more accurately estimate the maximum tolerated dose as compared to the standard Phase I dose escalation designs. Many variations have been published and discussed in the statistical literature, but there has not been as much practical advice for choosing design parameters and implementing the CRM. As a result, the CRM has not been as widely utilized as it could be for dose-finding studies. The goal of this paper is to provide a tutorial for those unfamiliar with the CRM who are either statisticians considering using the CRM for the first time, or investigators with some statistical background. This paper presents the original CRM, and then some of its modified versions. It also explains the specifications that define a CRM design, along with simulated examples of CRMs and standard designs, for illustration.
连续重新评估法（CRM）与其他适应性剂量探索研究设计一样，自奥奎利提出以来就颇受欢迎。临床试验人员采用它的几个原因在于，与标准的I期剂量递增设计相比，它往往会引发更少的毒性事件，并且能更准确地估计最大耐受剂量。统计文献中已发表并讨论了许多变体，但对于选择设计参数和实施CRM，却没有太多实用的建议。因此，CRM在剂量探索研究中的应用并未达到其应有的广泛程度。本文的目的是为那些不熟悉CRM的人提供一个教程，这些人要么是首次考虑使用CRM的统计学家，要么是有一定统计背景的研究人员。本文介绍了原始的CRM，以及它的一些修改版本。还解释了定义CRM设计的规范，并给出了CRM和标准设计的模拟示例以作说明。
