A Study on the Consistency Between Flagging by Statistical Tests and Biological Evaluation

Abstract

Statistical hypothesis tests are used as a flagging device to highlight differences worth further attention in the evaluation of repeated dose toxicity studies in the rat. Raw data of quantitative parameters of 19 regulatory toxicity studies were collected with their final interpretation of each study. An investigation was done on the consistency between flagging by statistical tests and biological significance by final interpretation. Williams’s test at 2.5% of the significance level showed as much accuracy (correct results compared with the sum of false negative and false positive results) as the rate of Dunnett’s test at the 5% significance level. Since a monotonic dose-response relationship is usually assumed in selection of dose levels, Williams’s test with ordered alternative hypotheses is recommended as a routine procedure instead of the currently used Dunnett’s test. A supplementary procedure, using Steel’s test, was shown to be effective for flagging unexpected ‘downturn’ dose response.