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      The Impact of Study Size on Meta-analyses: Examination of Underpowered Studies in Cochrane Reviews

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      1 , * , 1 , 2 , 3
      PLoS ONE
      Public Library of Science

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          Abstract

          Background

          Most meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published meta-analyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results.

          Methods and Findings

          For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as ≥50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the meta-analyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range −1% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease.

          Conclusions

          When at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews.

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          Author and article information

          Contributors
          Role: Editor
          Journal
          PLoS One
          PLoS ONE
          plos
          plosone
          PLoS ONE
          Public Library of Science (San Francisco, USA )
          1932-6203
          2013
          27 March 2013
          : 8
          : 3
          : e59202
          Affiliations
          [1 ]MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom
          [2 ]School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
          [3 ]Centre for Reviews and Dissemination, University of York, York, United Kingdom
          Copenhagen University Hospital Gentofte, Denmark
          Author notes

          Competing Interests: RMT and JPTH declare that no competing interests exist. The authors have the following interest. SMB holds Glaxo shares. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

          Conceived and designed the experiments: SMB JPTH. Performed the experiments: RMT SMB JPTH. Analyzed the data: RMT. Wrote the paper: RMT SMB JPTH.

          Article
          PONE-D-12-35850
          10.1371/journal.pone.0059202
          3609745
          23544056
          8ced240c-0240-47ea-afb1-f189f70e9ac5
          Copyright @ 2013

          This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

          History
          : 15 November 2012
          : 14 February 2013
          Page count
          Pages: 8
          Funding
          This work was funded by Medical Research Council grants U105285807 and U105260794. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
          Categories
          Research Article
          Biology
          Population Biology
          Epidemiology
          Epidemiological Methods
          Mathematics
          Statistics
          Biostatistics
          Statistical Methods
          Medicine
          Clinical Research Design
          Clinical Trials
          Epidemiology
          Meta-Analyses
          Statistical Methods
          Systematic Reviews
          Epidemiology
          Clinical Epidemiology
          Epidemiological Methods
          Non-Clinical Medicine
          Health Care Policy
          Comparative Effectiveness Research
          Science Policy
          Research Assessment
          Research Reporting Guidelines
          Research Validity

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