Systematic heterogenization for better reproducibility in animal experimentation
Systematic heterogenization for better reproducibility in animal experimentation
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DOI：
10.1038/laban.1330
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发表时间：
2017-09-01
期刊：
影响因子：
6.9
通讯作者：
Richter, S. Helene
中科院分区：
文献类型：
--
作者：
Richter, S. Helene
科学文献中充斥着讨论动物实验结果重复性差的文章，以及未能将临床前动物研究结果转化为人类临床试验的文章。评论家们甚至谈到了生命科学领域的“可再生性危机”，这个新奇的词汇越来越多地出现在许多影响力很大的期刊中。从愤世嫉俗的角度来看，费特的实验室定律“永远不能复制一个成功的实验”因此被赋予了全新的含义。到目前为止，动物实验的重复性差和翻译失败主要归因于动物数据的偏见、方法学陷阱、当前的出版伦理和动物福利限制。最近，标准化的概念也被确定为这些问题的一个潜在来源。通过减少实验内的差异，严格的标准化制度将推断限制在特定的实验条件下。然而，通过这种方式，个体的表型可塑性在很大程度上被忽略了，导致了统计上有意义但可能不相关的发现，这些发现在略有不同的条件下是不可重现的。相比之下，系统的异质性被提出为一个概念，以提高研究人群的代表性，有助于提高外部效度，从而改善重复性。虽然一些最初的异质化研究确实非常有希望，但仍然不清楚如何将这种方法以一种后勤上可行和有效的方式转化为实践。因此，需要进一步的研究来探索不同的异质性策略以及在动物实验中实现更好的重复性的替代途径。
The scientific literature is full of articles discussing poor reproducibility of findings from animal experiments as well as failures to translate results from preclinical animal studies to clinical trials in humans. Critics even go so far as to talk about a "reproducibility crisis" in the life sciences, a novel headword that increasingly finds its way into numerous high-impact journals. Viewed from a cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. So far, poor reproducibility and translational failures in animal experimentation have mostly been attributed to biased animal data, methodological pitfalls, current publication ethics and animal welfare constraints. More recently, the concept of standardization has also been identified as a potential source of these problems. By reducing within-experiment variation, rigorous standardization regimes limit the inference to the specific experimental conditions. In this way, however, individual phenotypic plasticity is largely neglected, resulting in statistically significant but possibly irrelevant findings that are not reproducible under slightly different conditions. By contrast, systematic heterogenization has been proposed as a concept to improve representativeness of study populations, contributing to improved external validity and hence improved reproducibility. While some first heterogenization studies are indeed very promising, it is still not clear how this approach can be transferred into practice in a logistically feasible and effective way. Thus, further research is needed to explore different heterogenization strategies as well as alternative routes toward better reproducibility in animal experimentation.