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Improving basic and translational science by accounting for litter-to-litter variation in animal models

机译:通过考虑动物模型中窝间差异来改善基础和转化科学

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Background Animals from the same litter are often more alike compared with animals from different litters. This litter-to-litter variation, or “litter effects”, can influence the results in addition to the experimental factors of interest. Furthermore, sometimes an experimental treatment can only be applied to whole litters rather than to individual offspring. An example is the valproic acid (VPA) model of autism, where VPA is administered to pregnant females thereby inducing the disease phenotype in the offspring. With this type of experiment the sample size is the number of litters and not the total number of offspring. If such experiments are not appropriately designed and analysed, the results can be severely biased as well as extremely underpowered. Results A review of the VPA literature showed that only 9% (3/34) of studies correctly determined that the experimental unit ( n ) was the litter and therefore made valid statistical inferences. In addition, litter effects accounted for up to 61% (p Conclusions Litter effects are common, large, and ignoring them can make replication of findings difficult and can contribute to the low rate of translating preclinical in vivo studies into successful therapies. Only a minority of studies reported using rigorous experimental methods, which is consistent with much of the preclinical in vivo literature.
机译:背景与来自不同垫料的动物相比,来自同一垫料的动物通常更相似。凋落物之间的差异或“凋落物效应”除了影响实验因素外,还会影响结果。此外,有时只能将实验性方法应用于整个产仔,而不能应用于单个后代。一个例子是自闭症的丙戊酸(VPA)模型,其中将VPA应用于怀孕的女性,从而在后代中诱发疾病表型。在这种类型的实验中,样本量是窝数而不是后代总数。如果没有对这些实验进行适当的设计和分析,则结果可能会产生严重偏差,甚至会导致功能不足。结果对VPA文献的回顾表明,只有9%(3/34)的研究正确地确定了实验单位(n)是垃圾,因此做出了有效的统计推断。此外,垫料的影响高达61%(p结论垫料的影响是普遍的,很大的,忽略它们会导致复制发现困难,并且可能会降低临床前体内研究成功转化为成功疗法的比率。使用严格的实验方法报道的大量研究与许多临床前体内文献一致。

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