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Open access

M. Iftakhar Alam

Abstract

The continual reassessment method is a model-based procedure, described in the literature, used to determine the maximum tolerated dose in phase I clinical trials. The maximum tolerated dose can also be found under the framework of D-optimum design, where information is gathered in such a way so that asymptotic variability in the parameter estimates in minimised. This paper investigates the two methods under some realistic settings to explore any potential differences between them. Simulation studies for six plausible dose-response scenarios show that D-optimum design can work well in comparison with the continual reassessment method in many cases. The D-optimum design is also found to allocate doses from the extremes of the design region to the patients in a trial.

Open access

M. Iftakhar Alam and Mohaimen Mansur

Summary

This paper investigates a stopping rule to be utilised in phase I clinical trials. The motivation is to develop a dynamic rule so that a trial stops early if the maximum tolerated dose lies towards the beginning of a dose region. Also, it will employ many patients if the maximum tolerated dose lies towards the end of a dose region. A two-parameter logistic model is assumed for the dose-response data. A trial is stopped early before reaching the maximum number of patients when the width of the Bayesian posterior probability interval of the slope parameter meets a desired value. Instead of setting a pre-specified width to stop at, we determine it based on the parameter estimate obtained after a reasonable number of steps in a trial. Simulation studies of six plausible dose-response scenarios show that the proposed stopping rule is capable of limiting the number of patients to be recruited depending on the underlying scenario. Although the rule is applied to a D-optimum design here, it will be equally applicable to other model-based designs.