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Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
bioRxiv - Scientific Communication and Education Pub Date : 2020-11-26 , DOI: 10.1101/2020.11.26.399584
Neil R. Smalheiser , Elena E. Graetz , Zhou Yu , Jing Wang

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.

中文翻译:

小鼠强迫游泳试验测定的效应量,样品量和功效:研究人员优化重现性的指南

最近的大量出版物记录了在科学再现性,功能和生物医学文章报告方面的严重问题,但科学家坚持了常规做法。为什么?我们检查了一种流行且重要的临床前测定,即用于测试推定的抗抑郁药的小鼠的强迫游泳试验(FST)。无论是在幼稚状态下还是在抑郁症或压力模型中对小鼠进行了测定,以及是否将小鼠与已知抗抑郁药作为试验药物(作为阳性对照)进行了对比,实验中观察到的平均效应大小确实非常大(1.5 –以科恩的d单位为2.5);大多数实验每组使用7-10只动物,它们确实具有足够的能力可靠地检测出这种程度的影响。我们建议,这至少可以部分解释为什么使用FST的研究人员无法直观地意识到他们的实验设计不足-即使正确的前瞻性设计每组需要约21-26只动物才能检测到至少大的影响(当未知测试剂的真实作用时,则以Cohen d单位为0.8)。我们的数据为寻求对FST进行预期功率估算的研究人员提供了明确的参数和指导。更普遍地讲,要改变科学家在计划实验中的现实行为,可能需要开发教育工具,使他们能够以直接和直观的方式主动可视化效应量,样本量,统计能力和可复制性之间的相互关系。
更新日期:2020-11-27
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