Issue 6, 2014

Statistical evaluation of toxicological bioassays – a review


The basic conclusions in almost all reports on new drug applications and in all publications in toxicology are based on statistical methods. However, serious contradictions exist in practice: designs with small samples sizes but use of asymptotic methods (i.e. constructed for larger sample sizes), statistically significant findings without biological relevance (and vice versa), proof of hazard vs. proof of safety, testing (e.g. no observed effect level) vs. estimation (e.g. benchmark dose), available statistical theory vs. related user-friendly software. In this review the biostatistical developments since about the year 2000 onwards are discussed, mainly structured for repeated-dose studies, mutagenicity, carcinogenicity, reproductive and ecotoxicological assays. A critical discussion is included on the unnecessarily conservative evaluation proposed in guidelines, the inadequate but almost always used proof of hazard approach, and the limitation of data-dependent decision-tree approaches.

Graphical abstract: Statistical evaluation of toxicological bioassays – a review

Article information

Article type
Review Article
16 May 2014
22 Jul 2014
First published
08 Aug 2014
This article is Open Access
Creative Commons BY-NC license

Toxicol. Res., 2014,3, 418-432