Reproducibility and replicability of rodent phenotyping in preclinical studies

Abstract

The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues. The general consensus was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, have a key role in identifying specific problems and promoting effective solutions. Replicability is closely related to validity, may affect generalizability and translation of findings, and has important ethical implications.

Keywords: Data sharing; False discoveries; GxE interaction; Heterogenization; Replicability; Reproducibility; Validity.

Fig. 1.

Comparing two genotypes G1 and G2, using two phenotypic measures 1 and 2, in three environments E1, E2 and E3. In the case of phenotype 1 (left) there is almost no interaction between genotype and environment (GxE). Note that the environment effect is large, but since it affects both genotypes in the same way it can be controlled using the same genotype as a reference for all other genotypes within the same environment. In the case of Phenotype 2 (right), there is a strong GxE effect, to the point that in E1, G1 is significantly larger than G2, while in E3, G1 is significantly smaller than G2 (“opposite significant”) and E2 does not have any effect. In this case an issue with replicability ensues, since the genotype effect is idiosyncratic to the specific combination of genotype and environment. and statistical reproducibility