What exactly is 'N' in cell culture and animal experiments?
What exactly is 'N' in cell culture and animal experiments?
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DOI：
10.1371/journal.pbio.2005282
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发表时间：
2018-04-01
期刊：
影响因子：
9.8
通讯作者：
Munafo, Marcus R.
中科院分区：
文献类型：
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作者：
Lazic, Stanley E.;Clarke-Williams, Charlie J.;Munafo, Marcus R.
生物学家通过扰乱生物实体或单位来确定实验效果。如果处理得当，实体-干预对的独立复制有助于样本大小(N)，并形成统计推断的基础。如果选择了错误的实体-干预对，实验就无法解决感兴趣的问题。我们调查了2011至2016年间发表的动物实验的随机样本，这些实验对父母进行了干预，并对后代进行了影响检查，因为监管机构为此类设计的复制提供了明确的指导方针。我们发现，只有22%的研究(95%CI=17%-29%)重复了正确的实体-干预对，从而做出了有效的统计推断。近一半的研究(46%，95%CI=38%-53%)有假复制，32%(95%CI=26%-39%)提供的信息不足以做出判断。假复制人为地夸大了样本大小，从而夸大了科学断言的证据，导致了假阳性。我们认为，区分生物单位、实验单位和观察单位可以澄清复制应该在哪里进行，描述真正复制的标准，并提供体外、体外和体内实验设计的具体例子。
Biologists determine experimental effects by perturbing biological entities or units. When done appropriately, independent replication of the entity-intervention pair contributes to the sample size (N) and forms the basis of statistical inference. If the wrong entity-intervention pair is chosen, an experiment cannot address the question of interest. We surveyed a random sample of published animal experiments from 2011 to 2016 where interventions were applied to parents and effects examined in the offspring, as regulatory authorities provide clear guidelines on replication with such designs. We found that only 22% of studies (95% CI = 17%-29%) replicated the correct entity-intervention pair and thus made valid statistical inferences. Nearly half of the studies (46%, 95% CI = 38%-53%) had pseudoreplication while 32% (95% CI = 26%-39%) provided insufficient information to make a judgement. Pseudoreplication artificially inflates the sample size, and thus the evidence for a scientific claim, resulting in false positives. We argue that distinguishing between biological units, experimental units, and observational units clarifies where replication should occur, describe the criteria for genuine replication, and provide concrete examples of in vitro, ex vivo, and in vivo experimental designs.