Statistics of Interlaboratory In Vitro Toxicological Studies

Abstract

Interlaboratory studies are common in toxicology, particularly for the introduction of alternative assays. Numerous papers are available on the statistical analysis of interlaboratory studies, but these deal primarily with the case of a replicated single sample studied in several laboratories. This approach can be used for some assays, but for the majority, the results will be unsatisfactory, i.e. involving great variability between both the dose groups and the laboratories. However, the primary objective of toxicological assays is to achieve similarity between the sizes of effects, rather than to determine absolute values. In the parametric model, the sizes of effects are the studentised differences from the negative control or, for the commonly used dose–response designs, the similarity of the slopes of the dose–response curves. Standard approaches for the estimation of intralaboratory and interlaboratory variability, including Mandel plots, are introduced, and new approaches are presented for demonstrating similarity of effect sizes, with or without assuming a dose–response model. One approach is based on a modification of the parallel-line assay, the other is based on a modification of the interaction contrasts of the analysis of variance. SAS programs are given for all approaches, and real data from an interlaboratory immunotoxicological study are analysed as a demonstration.