Journal of biopharmaceutical statistics
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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. ⋯ 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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Suppose, in a clinical trial, the interest is to show that the effectiveness of an experimental therapy is no worse than that of the standard therapy by more than a specified amount, say delta units. Blackwelder (1) discussed this problem in clinical trials where the outcome of interest is dichotomous. ⋯ In this paper, the asymmetric procedure of DeMets and Ware is modified to handle the case delta > 0. A two-stage procedure is considered in a drug interaction study that focuses on a specific side effect as the event of interest.