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Can trial quality be reliably assessed from published reports of cancer trials: evaluation of risk of bias assessments in systematic reviews

BMJ 2013; 346 doi: (Published 22 April 2013) Cite this as: BMJ 2013;346:f1798
  1. Claire L Vale, senior research scientist,
  2. Jayne F Tierney, senior research scientist ,
  3. Sarah Burdett, senior research scientist
  1. 1Meta-analysis Group, MRC Clinical Trials Unit, London WC2B 6NH, UK
  1. Correspondence to: C L Vale cv{at}
  • Accepted 12 March 2013


Objective To evaluate the reliability of risk of bias assessments based on published trial reports, for determining trial inclusion in meta-analyses.

Design Reliability evaluation of risk of bias assessments.

Data sources 13 published individual participant data (IPD) meta-analyses in cancer were used to source 95 randomised controlled trials.

Review methods Risk of bias was assessed using the Cochrane risk of bias tool (RevMan5.1) and accompanying guidance. Assessments were made for individual risk of bias domains and overall for each trial, using information from either trial reports alone or trial reports with additional information collected for IPD meta-analyses. Percentage agreements were calculated for individual domains and overall (<66%=low, ≥66%=fair, ≥90%=good). The two approaches were considered similarly reliable only when agreement was good.

Results Percentage agreement between the two methods for sequence generation and incomplete outcome data was fair (69.5% (95% confidence interval 60.2% to 78.7%) and 80.0% (72.0% to 88.0%), respectively). However, percentage agreement was low for allocation concealment, selective outcome reporting, and overall risk of bias (48.4% (38.4% to 58.5%), 42.1% (32.2% to 52.0%), and 54.7% (44.7% to 64.7%), respectively). Supplementary information reduced the proportion of unclear assessments for all individual domains, consequently increasing the number of trials assessed as low risk of bias (and therefore available for inclusion in meta-analyses) from 23 (23%) based on publications alone to 66 (66%) based on publications with additional information.

Conclusions Using cancer trial publications alone to assess risk of bias could be unreliable; thus, reviewers should be cautious about using them as a basis for trial inclusion, particularly for those trials assessed as unclear risk. Supplementary information from trialists should be sought to enable appropriate assessments and potentially reduce or overcome some risks of bias. Furthermore, guidance should ensure clarity on what constitutes risk of bias, particularly for the more subjective domains.


  • We thank the trialists who have previously supplied copies of trial protocols and forms for inclusion in IPD meta-analyses cited in this article.

  • Contributors: All authors were involved in the design and conduct of the analyses and interpretation of the results. CLV drafted the manuscript, which was revised by SB and JFT. All authors have read and agreed the final manuscript. CLV is the study guarantor.

  • Funding: This work was supported by the United Kingdom’s Medical Research Council.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: support from the Medical Research Council for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Data sharing: No additional data available.

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