title: Risk of bias in industry-funded oseltamivir trials: comparison of core reports versus full clinical study reports.
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.
  
  
  RESULTS
  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.
authors.affiliation: The Cochrane Collaboration, Roma, Italy.
authors.forename: Tom
authors.initials: T
authors.lastname: Jefferson
authors.affiliation: University of Queensland School of Population Health, Brisbane, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jones
authors.affiliation: Department of Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Doshi
authors.affiliation: Centre for Research in Evidence Based Practice, Bond University, Gold Coast, Australia.
authors.forename: Chris B
authors.initials: CB
authors.lastname: Del Mar
authors.affiliation: Japan Institute of Pharmacovigilance, Osaka, Japan.
authors.forename: Rokuro
authors.initials: R
authors.lastname: Hama
authors.affiliation: Department of Family Medicine, University of Washington, Seattle, Washington, USA Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Thompson
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Igho
authors.initials: I
authors.lastname: Onakpoya
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Heneghan
mesh_terms: D022126:Access to Information; D000998:Antiviral Agents / Q000627:therapeutic use*; D015982:Bias; D002986:Clinical Trials as Topic / Q000592:standards*; D004345:Drug Industry; D006801:Humans; D053139:Oseltamivir / Q000627:therapeutic use*; D011643:Publishing / Q000592:standards*; D012306:Risk; D013223:Statistics as Topic / Q000592:standards
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: STATISTICS & RESEARCH METHODS