Objectives: To provide information on the frequency and reasons for outcome reporting bias in clinical trials.
Design: Trial protocols were compared with subsequent publication(s) to identify any discrepancies in the outcomes reported, and telephone interviews were conducted with the respective trialists to investigate more extensively the reporting of the research and the issue of unreported outcomes.
Participants: Chief investigators, or lead or coauthors of trials, were identified from two sources: trials published since 2002 covered in Cochrane systematic reviews where at least one trial analysed was suspected of being at risk of outcome reporting bias (issue 4, 2006; issue 1, 2007, and issue 2, 2007 of the Cochrane library); and a random sample of trial reports indexed on PubMed between August 2007 and July 2008.
Setting: Australia, Canada, Germany, the Netherlands, New Zealand, the United Kingdom, and the United States.
Main outcome measures: Frequency of incomplete outcome reporting-signified by outcomes that were specified in a trial's protocol but not fully reported in subsequent publications-and trialists' reasons for incomplete reporting of outcomes.
Results: 268 trials were identified for inclusion (183 from the cohort of Cochrane systematic reviews and 85 from PubMed). Initially, 161 respective investigators responded to our requests for interview, 130 (81%) of whom agreed to be interviewed. However, failure to achieve subsequent contact, obtain a copy of the study protocol, or both meant that final interviews were conducted with 59 (37%) of the 161 trialists. Sixteen trial investigators failed to report analysed outcomes at the time of the primary publication, 17 trialists collected outcome data that were subsequently not analysed, and five trialists did not measure a prespecified outcome over the course of the trial. In almost all trials in which prespecified outcomes had been analysed but not reported (15/16, 94%), this under-reporting resulted in bias. In nearly a quarter of trials in which prespecified outcomes had been measured but not analysed (4/17, 24%), the "direction" of the main findings influenced the investigators' decision not to analyse the remaining data collected. In 14 (67%) of the 21 randomly selected PubMed trials, there was at least one unreported efficacy or harm outcome. More than a quarter (6/21, 29%) of these trials were found to have displayed outcome reporting bias.
Conclusion: The prevalence of incomplete outcome reporting is high. Trialists seemed generally unaware of the implications for the evidence base of not reporting all outcomes and protocol changes. A general lack of consensus regarding the choice of outcomes in particular clinical settings was evident and affects trial design, conduct, analysis, and reporting.