A Stepwise Confidence Interval Procedure Under Unknown Variances Based on an Asymmetric Loss Function for Toxicological Evaluation

Abstract

SummaryOne of the most important issues in toxicity studies is the identification of the equivalence of treatments with a placebo. Because it is unacceptable to declare non‐equivalent treatments to be equivalent, it is important to adopt a reliable statistical method to properly control the family‐wise error rate (FWER). In dealing with this issue, it is important to keep in mind that overestimating toxicity equivalence is a more serious error than underestimating toxicity equivalence. Consequently asymmetric loss functions are more appropriate than symmetric loss functions. Recently Tao, Tang & Shi (2010) developed a new procedure based on an asymmetric loss function. However, their procedure is somewhat unsatisfactory because it assumes that the variances of various dose levels are known. This assumption is restrictive for some applications. In this study we propose an improved approach based on asymmetric confidence intervals without the restrictive assumption of known variances. The asymmetry guarantees reliability in the sense that the FWER is well controlled. Although our procedure is developed assuming that the variances of various dose levels are unknown but equal, simulation studies show that our procedure still performs quite well when the variances are unequal.