Similarity of multiple dose-response curves in interlaboratory studies in regulatory toxicology

TL;DR

This paper presents a statistical approach using dose-by-laboratory interaction contrasts to assess the similarity of dose-response curves across laboratories in regulatory toxicology, demonstrated with in-vitro assay data.

Contribution

It introduces a method employing Williams-type contrasts and open-source R packages to evaluate curve similarity, addressing the challenge of interpretation without predefined thresholds.

Findings

Effective use of CRAN packages statint and multcomp for analysis

Application to in-vitro Ames MPF assay data

Facilitates assessment of interlaboratory curve similarity

Abstract

To claim similarity of multiple dose-response curves in interlaboratory studies in regulatory toxicology is a relevant issue during the assay validation process. Here we demonstrated the use of dose-by-laboratory interaction contrasts, particularly Williams-type by total mean contrasts. With the CRAN packages statint and multcomp in the open-source software R the estimation of adjusted p-values or compatible simultaneous confidence intervals is relatively easy. The interpretation in terms of global or partial equivalence, i.e. similarity, is challenging, because thresholds are not available a-priori. This approach is demonstrated by selected in-vitro Ames MPF assay data.