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Never replicate a successful experiment? Standardization, heterogenization and reproducibility in animal experiments

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基本信息

批准号：
283089959
负责人：
Professorin Dr. Sophie Helene Richter
金额：
--
依托单位：
Abteilung für Verhaltensbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/283089959?language=en
关键词：
Never replicate successful experiment Standardization

项目摘要

Reproducibility is a cornerstone of any scientific method, especially in animal research where the lives of the animals are highly valuable. Traditionally, animals, husbandry and test procedures are standardized in animal experimentation to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioural tests, accounting for poor reproducibility. However, despite the widespread recognition of these problems, it is still not clear how to conduct an experiment within a single lab that may result in more stable results across studies. With the aim of making study populations more representative, systematic variation within studies (i.e. heterogenization) rather than rigorous standardization has been proposed to be a powerful tool to improve the reproducibility and the translational value of research findings from animal experiments Thus, the overall aim of the present project is to develop and validate practicable and effective heterogenization strategies that may serve to improve the reproducibility and translational value of research findings from animal experiments. In a series of pre-experiments, three different heterogenization strategies will be investigated and compared with respect to their effectiveness before testing the best strategy in a real multi-laboratory-setting. Factors that will be used for systematic heterogenization are (i) batch, (ii) day time, and (iii) experimenter, since all three factors are known to greatly influence the outcome of an experiment. To mimic a genotype effect, three commonly used inbred strains of mice (C57BL/6, DBA/2, Balb/c) will be examined in a battery of six different behavioural tests. Since limited reproducibility and translational failures has been particularly discussed in the context of behavioural phenotyping studies, we will restrict our analysis to behavioural outcome measures. Based on previous findings, we hypothesize that heterogenized experiments will yield more stable results across experiments than standardized ones.

可重复性是任何科学方法的基石，特别是在动物研究中，动物的生命是非常宝贵的。传统上，在动物实验中，动物、畜牧业和测试程序都是标准化的，以最大限度地提高测试灵敏度，最大限度地减少动物的使用，假设这也将保证可重复性。然而，通过减少实验内的变化，标准化可以限制对特定实验条件的推断。事实上，我们最近在老鼠身上的研究表明，标准化可能会在行为测试中产生虚假的结果，从而导致重复性差。然而，尽管人们普遍认识到这些问题，但尚不清楚如何在单个实验室内进行实验，从而在多个研究中得出更稳定的结果。为了使研究群体更具代表性，研究中的系统变异（即异质化）而不是严格的标准化被认为是提高动物实验研究结果可重复性和转化价值的有力工具。本项目的总体目标是开发和验证可行和有效的异质化策略，以提高动物实验研究结果的可重复性和转化价值。在一系列的预实验中，三种不同的异质化策略将被调查并比较其有效性，然后在真实的多实验室环境中测试最佳策略。将用于系统异质化的因素是(i)批次，（ii）白天时间，（iii）实验者，因为已知这三个因素对实验结果有很大影响。为了模拟基因型效应，将对三种常用的近交系小鼠（C57BL/6、DBA/2、Balb/c）进行六组不同的行为测试。由于在行为表型研究的背景下特别讨论了有限的可重复性和翻译失败，我们将把我们的分析限制在行为结果测量上。基于先前的研究结果，我们假设异质化实验将比标准化实验产生更稳定的结果。