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The need for randomization in animal trials: an overview of systematic reviews.

Hirst JA, Howick J, Aronson JK, Roberts N, Perera R, Koshiaris C, Heneghan C - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.

ABSTRACT

Background and objectives: 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.

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Flowchart of identified and included studies.
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pone-0098856-g001: Flowchart of identified and included studies.

Mentions: We identified 238 articles from our electronic search, and a further 24 articles by hand searching references and contacting CAMARADES authors. Two authors (JH, JAH) excluded 199 articles after reading titles and abstracts. We assessed the full text of the remaining 63 articles and excluded a further 32 for not including outcome data. CAMARADES authors generously shared data from 19 reviews in which data were not included in the published reports. We were left with 31 systematic reviews involving 7339 comparisons (estimated 123,437 animals) to include in the meta-analysis (see Figure 1). Characteristics of the 31 included reviews are shown in Table 1, and our data are available freely from the authors.


The need for randomization in animal trials: an overview of systematic reviews.

Hirst JA, Howick J, Aronson JK, Roberts N, Perera R, Koshiaris C, Heneghan C - PLoS ONE (2014)

Flowchart of identified and included studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048216&req=5

pone-0098856-g001: Flowchart of identified and included studies.
Mentions: We identified 238 articles from our electronic search, and a further 24 articles by hand searching references and contacting CAMARADES authors. Two authors (JH, JAH) excluded 199 articles after reading titles and abstracts. We assessed the full text of the remaining 63 articles and excluded a further 32 for not including outcome data. CAMARADES authors generously shared data from 19 reviews in which data were not included in the published reports. We were left with 31 systematic reviews involving 7339 comparisons (estimated 123,437 animals) to include in the meta-analysis (see Figure 1). Characteristics of the 31 included reviews are shown in Table 1, and our data are available freely from the authors.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.

ABSTRACT

Background and objectives: 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.

Show MeSH
Related in: MedlinePlus