  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.
