Dose finding using the biased coin up-and-down design and isotonic regression.
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.
Stylianou
Mario
M
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. StylianM@nih.gov
Flournoy
Nancy
N
D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D003198:Computer Simulation; D006801:Humans; D016015:Logistic Models; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D013223:Statistics as Topic / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods
D004364:Pharmaceutical Preparations