title: Systematic review of the empirical evidence of study publication bias and outcome reporting bias.
abstract: BACKGROUND
  The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention.
  
  
  RESULTS
  We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies.
  
  
  CONCLUSIONS
  Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.
authors.affiliation: Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool, United Kingdom. kerry.dwan@liverpool.ac.uk
authors.forename: Kerry
authors.initials: K
authors.lastname: Dwan
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Altman
authors.forename: Juan A
authors.initials: JA
authors.lastname: Arnaiz
authors.forename: Jill
authors.initials: J
authors.lastname: Bloom
authors.forename: An-Wen
authors.initials: AW
authors.lastname: Chan
authors.forename: Eugenia
authors.initials: E
authors.lastname: Cronin
authors.forename: Evelyne
authors.initials: E
authors.lastname: Decullier
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook
authors.forename: Erik
authors.initials: E
authors.lastname: Von Elm
authors.forename: Carrol
authors.initials: C
authors.lastname: Gamble
authors.forename: Davina
authors.initials: D
authors.lastname: Ghersi
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: John
authors.initials: J
authors.lastname: Simes
authors.forename: Paula R
authors.initials: PR
authors.lastname: Williamson