Communications for Statistical Applications and Methods

The Korean Statistical Society (한국통계학회)
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Estimation of Maximal Tolerated Dose in Sequential Phase I Clinical Trials

  • Park, In-Hye (Department of Biostatistics, Catholic University) ;
  • Song, Hae-Hiang (Professor, Department of Biostaitistics, Catholic University)
  • Published : 1999.08.01
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Abstract

The principal aim of a sequential phase I clinical trial in which the toxicity reponses of a group of patient(s) determine the dose level of the next patient(s) group is to estimate the maximal tolerated dose(MTD) of a new drug, In this paper we compared with a simulation study the performance of the MTD estimates that are determined by a stopping rule in a design and also those that are determined by analyzing the data after a clinical trial is terminated. To the latter belong the mean median mode and maximum likelihood estimates. For the Standard Methods the stopping rule MTD is quite inefficient but the median MTD has a best efficiency and is robust with respect to the three different toxicity curves. The problem of non-convergence of MLE MTD is severe. A more improved MTD estimate is produced by combining the advantages of the various MTD estimates and its efficiency is better than the single median MTD estimate especially for the toxicity curve of an unlucky choice of dose levels. The simulation results suggest that simple types of phase I designs can be combined with relatively standard analytic techniques to provide a more efficient MTD estimate.

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