Practical modifications of the continual reassessment method for phase I cancer clinical trials.
The continual reassessment method (1) (CRM) for phase I cancer trials provides improved estimation of the maximum tolerated dose (MTD), and fewer patients receive ineffective dose levels compared to the traditionally used design. However, the CRM has not gained acceptance in practice owing to concerns with administering dose levels that are too toxic. In this article, several conservative modifications of the CRM are introduced. The result is a procedure that improves estimation of the MTD and decreases the use of ineffective doses, without significantly increasing the use of toxic dose levels. The CRM with modification outperforms the traditional method in a simulation study.
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Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012107:Research Design / Q000706:statistics & numerical data*; D012984:Software
D000970:Antineoplastic Agents