title: The need for randomization in animal trials: an overview of systematic reviews.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Hirst
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Howick
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Aronson
authors.affiliation: Bodleian Libraries, University of Oxford, Oxford, United Kingdom.
authors.forename: Nia
authors.initials: N
authors.lastname: Roberts
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Rafael
authors.initials: R
authors.lastname: Perera
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Koshiaris
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Carl
authors.initials: C
authors.lastname: Heneghan
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D015982:Bias; D012107:Research Design; D012196:Review Literature as Topic