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Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility

A recent flood of publications has documented serious problems in scientific reproducibility, power, and reporting of biomedical articles, yet scientists persist in their usual practices. Why? We examined a popular and important preclinical assay, the Forced Swim Test (FST) in mice used to test puta...

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Detalles Bibliográficos
Autores principales: Smalheiser, Neil R., Graetz, Elena E., Yu, Zhou, Wang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904226/
https://www.ncbi.nlm.nih.gov/pubmed/33626103
http://dx.doi.org/10.1371/journal.pone.0243668
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author Smalheiser, Neil R.
Graetz, Elena E.
Yu, Zhou
Wang, Jing
author_facet Smalheiser, Neil R.
Graetz, Elena E.
Yu, Zhou
Wang, Jing
author_sort Smalheiser, Neil R.
collection PubMed
description A recent flood of publications has documented serious problems in scientific reproducibility, power, and reporting of biomedical articles, yet scientists persist in their usual practices. Why? We examined a popular and important preclinical assay, the Forced Swim Test (FST) in mice used to test putative antidepressants. Whether the mice were assayed in a naïve state vs. in a model of depression or stress, and whether the mice were given test agents vs. known antidepressants regarded as positive controls, the mean effect sizes seen in the experiments were indeed extremely large (1.5–2.5 in Cohen’s d units); most of the experiments utilized 7–10 animals per group which did have adequate power to reliably detect effects of this magnitude. We propose that this may at least partially explain why investigators using the FST do not perceive intuitively that their experimental designs fall short—even though proper prospective design would require ~21–26 animals per group to detect, at a minimum, large effects (0.8 in Cohen’s d units) when the true effect of a test agent is unknown. Our data provide explicit parameters and guidance for investigators seeking to carry out prospective power estimation for the FST. More generally, altering the real-life behavior of scientists in planning their experiments may require developing educational tools that allow them to actively visualize the inter-relationships among effect size, sample size, statistical power, and replicability in a direct and intuitive manner.
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spelling pubmed-79042262021-03-03 Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility Smalheiser, Neil R. Graetz, Elena E. Yu, Zhou Wang, Jing PLoS One Research Article A recent flood of publications has documented serious problems in scientific reproducibility, power, and reporting of biomedical articles, yet scientists persist in their usual practices. Why? We examined a popular and important preclinical assay, the Forced Swim Test (FST) in mice used to test putative antidepressants. Whether the mice were assayed in a naïve state vs. in a model of depression or stress, and whether the mice were given test agents vs. known antidepressants regarded as positive controls, the mean effect sizes seen in the experiments were indeed extremely large (1.5–2.5 in Cohen’s d units); most of the experiments utilized 7–10 animals per group which did have adequate power to reliably detect effects of this magnitude. We propose that this may at least partially explain why investigators using the FST do not perceive intuitively that their experimental designs fall short—even though proper prospective design would require ~21–26 animals per group to detect, at a minimum, large effects (0.8 in Cohen’s d units) when the true effect of a test agent is unknown. Our data provide explicit parameters and guidance for investigators seeking to carry out prospective power estimation for the FST. More generally, altering the real-life behavior of scientists in planning their experiments may require developing educational tools that allow them to actively visualize the inter-relationships among effect size, sample size, statistical power, and replicability in a direct and intuitive manner. Public Library of Science 2021-02-24 /pmc/articles/PMC7904226/ /pubmed/33626103 http://dx.doi.org/10.1371/journal.pone.0243668 Text en © 2021 Smalheiser et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Smalheiser, Neil R.
Graetz, Elena E.
Yu, Zhou
Wang, Jing
Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
title Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
title_full Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
title_fullStr Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
title_full_unstemmed Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
title_short Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
title_sort effect size, sample size and power of forced swim test assays in mice: guidelines for investigators to optimize reproducibility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904226/
https://www.ncbi.nlm.nih.gov/pubmed/33626103
http://dx.doi.org/10.1371/journal.pone.0243668
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