Evaluation of histological findings with severity grade, to analyze toxicology in-vivo studies

TL;DR

This paper evaluates statistical methods for analyzing graded histopathological findings in in-vivo toxicology studies, proposing a new approach for small sample sizes and interpretability.

Contribution

It introduces a novel simultaneous testing method for graded histological data, enhancing analysis of toxicological effects in small-sample studies.

Findings

Compared different statistical methods for graded data

Proposed a new simultaneous testing approach

Provided R code for practical implementation

Abstract

In-vivo toxicological studies are characterized by multiple primary endpoints with quite different scales. Whereas guidelines and publications provide various statistical tests for normally distributed endpoints (such as organ weights) and proportions (such as tumor rates), few approaches are available for graded histopathological findings, such as 0, +, ++, +++. This represents a basic contradiction of the statistical analysis because these graded findings sometimes show a high predictive value for potential toxic effects. Here we discuss different methods comparatively, especially from the viewpoints of i) designs for very small sample sizes and ii) interpretability by toxicologists. A new approach is recommended where a simultaneous test is performed over all class combinations of score levels, such as (0, +) vs (++, +++). Corresponding R code is provided by way of a data example.