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Updated: Sep 21, 2026

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Estimating the probability of toxicity at the target dose following an up-and-down design
Mario Stylianou1, Michael Proschan, Nancy Flournoy
1Office of Biostatistics Research, National Heart, Lung, and Blood Institute/NIH, 6701 Rockledge Drive, Room 8220, Bethesda, MD 20892, U.S.A. StylianM@nih.gov
Abstract:
One of the most important aspects of a phase I trial or other acute toxicity study is estimating accurately the probability of toxicity that is associated with the recommended dose. We use the biased coin up-and-down design to allocate and isotonic regression to estimate toxicity probabilities and determine the recommended dose. We then derive, using bootstrap methods, an estimate of the probability of toxicity at the recommended dose. Small sample properties of this estimator are also evaluated. Published in 2003 by John Wiley & Sons, Ltd.
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