Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Bodleian Libraries, University of Oxford, Oxford, United Kingdom.
PLoS One. 2014 Jun 6;9(6):e98856. doi: 10.1371/journal.pone.0098856. eCollection 2014.
Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition.
We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment.
Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective.
Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.
随机化、分配隐藏和盲法结局评估已被证明可减少人类研究中的偏倚。来自合作式荟萃分析和动物实验数据评估（CAMARADES）协作的作者最近发现，这些特征可防止动物卒中研究中的偏倚。我们将 CAMARADES 的工作范围扩展到包括任何疾病的治疗方法的研究。
我们进行了系统综述概述。我们在 Medline 和 Embase 中检索了动物研究的系统综述，这些研究测试了任何干预措施（与任何对照相比），并包括任何疾病领域和结局。我们纳入了比较随机与非随机（但其他方面得到控制）、分配隐藏与不隐藏、结局评估盲法与非盲法的综述。
31 篇系统综述符合我们的纳入标准：20 篇综述调查了实验性卒中的治疗方法，4 篇综述调查了脊髓疾病的治疗方法，1 篇综述分别调查了骨癌、脑出血、胶质母细胞瘤、多发性硬化症、帕金森病和急诊医学中治疗方法的治疗方法。在我们的样本中，29%的研究报告了随机化，15%的研究报告了分配隐藏，35%的研究报告了盲法结局评估。我们在荟萃分析中汇总了结果，在主要分析中发现，未随机化显著增加了效应大小，而分配隐藏和盲法则没有。在二次分析中，我们发现随机化、分配隐藏和盲法降低了效应大小，尤其是在结局为主观时。
我们的研究表明，在广泛的结局和疾病领域中，动物研究需要随机化、分配隐藏和盲法结局评估。由于人类研究通常基于动物研究的结果，因此我们的结果表明，不适当的有偏倚的动物研究不应被允许作为人类试验的理由的一部分。
