A Reaction Norm Perspective on Reproducibility

Voelkl, Bernhard; Würbel, Hanno (January 2019). A Reaction Norm Perspective on Reproducibility (bioRxiv 510941). Cold Spring Harbor Laboratory 10.1101/510941

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Reproducibility in biomedical research, and more specifically in preclinical animal research, has been seriously questioned. Several cases of spectacular failures to replicate findings published in the primary scientific literature have led to a perceived reproducibility crisis. Diverse threats to reproducibility have been proposed, including lack of scientific rigour, low statistical power, publication bias, analytical flexibility and fraud. An important aspect that is generally overlooked is the lack of external validity caused by rigorous standardization of both the animals and the environment. Here, we argue that a reaction norm approach to phenotypic variation, acknowledging gene-by-environment interactions, can help us seeing reproducibility of animal experiments in a new light. We illustrate how dominating environmental effects can affect inference and effect size estimates of studies and how elimination of dominant factors through standardization affects the nature of the expected phenotype variation. We do this by introducing a construct that we dubbed the reaction norm of small effects. Finally, we discuss the consequences of a reaction norm of small effects for statistical analysis, specifically for random effect latent variable models and the random lab model.

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