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Dose Finding Using the Biased Coin Up-and-Down Design and Isotonic Regression

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We are interested in finding a dose that has a prespecified toxicity rate in the target population. In this article, we investigate five estimators of the target dose to be used with the up-and-down biased coin design (BCD) Introduced By Durham and Flournoy (1994, Statistical Decision Theory and Related Topics). These estimators are derived using maximum likelihood, weighted least squares, sample averages, and isotonic regression. A linearly interpolated isotonic regression estimate is shown to be simple to derive and to perform as well as or better than the other target dose estimators in terms of mean square error and average number of subjects needed for convergence in most scenarios studied.

Keywords: Adaptive designs; Inference for stochastic processes; Logistic regression; Quantal estimation; Random walk designs; Response-driven designs; Toxicity studies

Document Type: Research Article


Affiliations: 1: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, U.S.A., Email: 2: Department of Mathematics and Statistics, American University, Washington, B.C. 20016, U.S.A.

Publication date: March 1, 2002

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