Article Text

Risk of bias in industry-funded oseltamivir trials: comparison of core reports versus full clinical study reports
  1. Tom Jefferson1,
  2. Mark A Jones2,
  3. Peter Doshi3,
  4. Chris B Del Mar4,
  5. Rokuro Hama5,
  6. Matthew J Thompson6,7,
  7. Igho Onakpoya7,
  8. Carl J Heneghan7
  1. 1The Cochrane Collaboration, Roma, Italy
  2. 2University of Queensland School of Population Health, Brisbane, Australia
  3. 3Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
  4. 4Centre for Research in Evidence Based Practice, Bond University, Gold Coast, Australia
  5. 5Japan Institute of Pharmacovigilance, Osaka, Japan
  6. 6Department of Family Medicine, University of Washington, Seattle, Washington, USA
  7. 7Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  1. Correspondence to Dr Tom Jefferson, The Cochrane Collaboration, Via Puglie 23, Roma 00187, Italy; jefferson.tom{at}gmail.com

Abstract

Background The Cochrane risk of bias tool is a prominent instrument used to evaluate potential biases in clinical trials. In three updates of our Cochrane review on neuraminidase inhibitors, we assessed risk of bias on the same trials using different levels of detail: the trials in journal publications, in core reports, and in full clinical study reports. Here we analyse whether progressively greater amounts of information and detail in full clinical study reports (including trial protocols, statistical analysis plans, certificates of analyses, individual participant data listings and randomisation lists) affected our risk of bias assessments.

Methods and findings We used the Cochrane risk of bias tool to assess and compare risk of bias in 14 oseltamivir trials (reported in 10 clinical study reports) obtained from the European Medicines Agency (EMA) and the manufacturer, Roche. With more detailed information, reported in clinical study reports, no previous assessment of ‘high’ risk of bias was reclassified as ‘low’ or ‘unclear’ in the main analysis, and over half (55%, 34/62) of the previous assessments of ‘low’ risk of bias were reclassified as ‘high’. Most assessments of ‘unclear’ risk of bias (67%, or 28/42) were reclassified as ‘high’ risk of bias when our judgements were based on full clinical study reports. The limits of our study were our relative inexperience in dealing with large information sets, sometimes subjective bias judgements and focus on industry trials. Comparison with journal publications was not possible because of the low number of trials published.

Conclusions We found that as information increased in the document, this increased our assessment of bias. This may mean that risk of bias has been insufficiently assessed in Cochrane reviews based on journal publications.

  • STATISTICS & RESEARCH METHODS

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