Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor.
Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor.
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DOI：
10.1371/journal.pbio.2000598
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发表时间：
2016-12
期刊：
影响因子：
9.8
通讯作者：
Würbel H
中科院分区：
文献类型：
--
作者：
Vogt L;Reichlin TS;Nathues C;Würbel H
越来越多的证据表明，临床前动物研究存在高偏倚风险，对已发表研究结果的科学有效性和可重复性提出了质疑。系统性综述发现，已发表文献中针对偏倚风险的措施报告率较低（例如，随机化、盲法、样本量计算）以及低报告率与夸大的治疗效果之间的相关性。大多数动物研究经过同行评审或伦理审查，这将提供在研究进行之前的早期阶段发现偏见风险的可能性。例如，在瑞士，动物实验根据研究方案的详细说明和危害-效益分析获得许可。因此，我们筛选了提交给瑞士当局的动物实验申请（n = 1，277）对于使用七种基本措施对抗偏倚的比率，（分配隐藏、设盲、随机化、样本量计算、入选/排除标准、主要结局变量，和统计分析计划）进行了描述，并将其与具有代表性的出版物子样本（n = 50），其由这些申请中描述的研究产生。针对偏倚的措施描述率非常低，平均范围从统计分析计划的2.4%到动物实验应用中主要结局变量的19%，从样本量计算的0.0%到这些实验出版物中统计分析计划的34%。计算内部效度得分（IVS）的基础上的比例的七个措施，对偏见，我们发现一个弱的正相关关系IVS的应用和出版物（斯皮尔曼的rho = 0.34，p = 0.014），表明这些措施的描述率在应用程序部分预测其在出版物中的报告率。这些结果表明，批准动物实验的当局缺乏有关实验行为的重要信息，这些信息决定了研究结果的科学有效性，而这些信息对于在危害-效益分析中赋予研究效益的权重可能至关重要。类似的手稿被接受出版，尽管对偏见的措施报告不佳，动物实验的申请往往是基于隐含的信心，而不是明确的科学严谨性证据批准。我们的研究结果对目前的动物实验授权程序以及科学出版物的同行评审程序提出了严重质疑，从长远来看，这可能会破坏研究的可信度。发展许多国家已经存在的现有授权程序，建立动物研究预登记制度，是改革该制度的一个有希望的途径。这不仅有利于动物实验结果的科学有效性，而且有助于避免由于没有结论的研究而对动物造成不必要的伤害。研究结果的科学有效性取决于科学的严谨性，包括避免偏倚的措施，例如将动物随机分配到治疗组（随机化）和在不知道动物属于哪个治疗组的情况下评估结局指标（设盲）。然而，在出版物中很少报告针对偏倚的措施，并且系统性综述发现，不良报告与较大的治疗效果相关，表明偏倚。在这里，我们研究了偏倚风险是否可以从提交伦理审查的研究方案中预测。我们评估了在瑞士提交批准的研究方案和这些研究产生的出版物中提到的七项基本措施。在研究方案（2%-19%）和出版物（0%-34%）中，均以非常低的比例提及了偏倚措施。然而，我们发现了弱的正相关性，表明研究方案中提及的偏倚措施的发生率预测了出版物中报告的发生率。我们的研究结果表明，动物实验往往是基于信心，而不是科学严谨性的证据，这可能会损害科学的有效性，并诱导不必要的伤害动物造成的不确定的研究。
Accumulating evidence indicates high risk of bias in preclinical animal research, questioning the scientific validity and reproducibility of published research findings. Systematic reviews found low rates of reporting of measures against risks of bias in the published literature (e.g., randomization, blinding, sample size calculation) and a correlation between low reporting rates and inflated treatment effects. That most animal research undergoes peer review or ethical review would offer the possibility to detect risks of bias at an earlier stage, before the research has been conducted. For example, in Switzerland, animal experiments are licensed based on a detailed description of the study protocol and a harm–benefit analysis. We therefore screened applications for animal experiments submitted to Swiss authorities (n = 1,277) for the rates at which the use of seven basic measures against bias (allocation concealment, blinding, randomization, sample size calculation, inclusion/exclusion criteria, primary outcome variable, and statistical analysis plan) were described and compared them with the reporting rates of the same measures in a representative sub-sample of publications (n = 50) resulting from studies described in these applications. Measures against bias were described at very low rates, ranging on average from 2.4% for statistical analysis plan to 19% for primary outcome variable in applications for animal experiments, and from 0.0% for sample size calculation to 34% for statistical analysis plan in publications from these experiments. Calculating an internal validity score (IVS) based on the proportion of the seven measures against bias, we found a weak positive correlation between the IVS of applications and that of publications (Spearman’s rho = 0.34, p = 0.014), indicating that the rates of description of these measures in applications partly predict their rates of reporting in publications. These results indicate that the authorities licensing animal experiments are lacking important information about experimental conduct that determines the scientific validity of the findings, which may be critical for the weight attributed to the benefit of the research in the harm–benefit analysis. Similar to manuscripts getting accepted for publication despite poor reporting of measures against bias, applications for animal experiments may often be approved based on implicit confidence rather than explicit evidence of scientific rigor. Our findings shed serious doubt on the current authorization procedure for animal experiments, as well as the peer-review process for scientific publications, which in the long run may undermine the credibility of research. Developing existing authorization procedures that are already in place in many countries towards a preregistration system for animal research is one promising way to reform the system. This would not only benefit the scientific validity of findings from animal experiments but also help to avoid unnecessary harm to animals for inconclusive research. Scientific validity of research findings depends on scientific rigor, including measures to avoid bias, such as random allocation of animals to treatment groups (randomization) and assessing outcome measures without knowing to which treatment groups the animals belong (blinding). However, measures against bias are rarely reported in publications, and systematic reviews found that poor reporting was associated with larger treatment effects, suggesting bias. Here we studied whether risk of bias could be predicted from study protocols submitted for ethical review. We assessed mention of seven basic measures against bias in study protocols submitted for approval in Switzerland and in publications resulting from these studies. Measures against bias were mentioned at very low rates both in study protocols (2%–19%) and in publications (0%–34%). However, we found a weak positive correlation, indicating that the rates at which measures against bias were mentioned in study protocols predicted the rates at which they were reported in publications. Our results indicate that animal experiments are often licensed based on confidence rather than evidence of scientific rigor, which may compromise scientific validity and induce unnecessary harm to animals caused by inconclusive research.
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影响因子：
4.4
作者：
Bebarta, V;Luyten, D;Heard, K
通讯作者：
Heard, K
影响因子：
15.8
作者：
Ioannidis, JPA
通讯作者：
Ioannidis, JPA
影响因子：
64.8
作者：
Landis, Story C.;Amara, Susan G.;Asadullah, Khusru;Austin, Chris P.;Blumenstein, Robi;Bradley, Eileen W.;Crystal, Ronald G.;Darnell, Robert B.;Ferrante, Robert J.;Fillit, Howard;Finkelstein, Robert;Fisher, Marc;Gendelman, Howard E.;Golub, Robert M.;Goudreau, John L.;Gross, Robert A.;Gubitz, Amelie K.;Hesterlee, Sharon E.;Howells, David W.;Huguenard, John;Kelner, Katrina;Koroshetz, Walter;Krainc, Dimitri;Lazic, Stanley E.;Levine, Michael S.;Macleod, Malcolm R.;McCall, John M.;Moxley, Richard T., III;Narasimhan, Kalyani;Noble, Linda J.;Perrin, Steve;Porter, John D.;Steward, Oswald;Unger, Ellis;Utz, Ursula;Silberberg, Shai D.
通讯作者：
Silberberg, Shai D.
DOI：
10.1207/s15327957pspr0203_4
发表时间：
1998-01-01
期刊：
Personality and social psychology review : an official journal of the Society for Personality and Social Psychology, Inc
影响因子：
--
作者：
Kerr, N L
通讯作者：
Kerr, N L
影响因子：
3.7
作者：
Kilkenny C;Parsons N;Kadyszewski E;Festing MF;Cuthill IC;Fry D;Hutton J;Altman DG
通讯作者：
Altman DG