title: Comparison of registered and published outcomes in randomized controlled trials: a systematic review.
abstract: BACKGROUND
  Clinical trial registries can improve the validity of trial results by facilitating comparisons between prospectively planned and reported outcomes. Previous reports on the frequency of planned and reported outcome inconsistencies have reported widely discrepant results. It is unknown whether these discrepancies are due to differences between the included trials, or to methodological differences between studies. We aimed to systematically review the prevalence and nature of discrepancies between registered and published outcomes among clinical trials.
  
  
  METHODS
  We searched MEDLINE via PubMed, EMBASE, and CINAHL, and checked references of included publications to identify studies that compared trial outcomes as documented in a publicly accessible clinical trials registry with published trial outcomes. Two authors independently selected eligible studies and performed data extraction. We present summary data rather than pooled analyses owing to methodological heterogeneity among the included studies.
  
  
  RESULTS
  Twenty-seven studies were eligible for inclusion. The overall risk of bias among included studies was moderate to high. These studies assessed outcome agreement for a median of 65 individual trials (interquartile range [IQR] 25-110). The median proportion of trials with an identified discrepancy between the registered and published primary outcome was 31%; substantial variability in the prevalence of these primary outcome discrepancies was observed among the included studies (range 0% (0/66) to 100% (1/1), IQR 17-45%). We found less variability within the subset of studies that assessed the agreement between prospectively registered outcomes and published outcomes, among which the median observed discrepancy rate was 41% (range 30% (13/43) to 100% (1/1), IQR 33-48%). The nature of observed primary outcome discrepancies also varied substantially between included studies. Among the studies providing detailed descriptions of these outcome discrepancies, a median of 13 % of trials introduced a new, unregistered outcome in the published manuscript (IQR 5-16%).
  
  
  CONCLUSIONS
  Discrepancies between registered and published outcomes of clinical trials are common regardless of funding mechanism or the journals in which they are published. Consistent reporting of prospectively defined outcomes and consistent utilization of registry data during the peer review process may improve the validity of clinical trial publications.
authors.affiliation: Department of Emergency Medicine, Cooper Medical School of Rowan University, One Cooper Plaza, Suite 152, Camden, NJ, 08103, USA. Jones-Christopher@cooperhealth.edu.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Jones
authors.affiliation: School of Medicine, University of North Carolina Chapel Hill, 321 S Columbia St, Chapel Hill, NC, 27516, USA. Lukasgkeil@gmail.com.
authors.forename: Lukas G
authors.initials: LG
authors.lastname: Keil
authors.affiliation: Department of Biology, University of North Carolina Chapel Hill, Coker Hall, 120 South Rd, Chapel Hill, NC, 27599, USA. Wesleych@live.unc.edu.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Holland
authors.affiliation: Department of Medicine, University of North Carolina Chapel Hill, 125 MacNider Hall, CB 7005, Chapel Hill, NC, 27599, USA. Melissa_Caughey@med.unc.edu.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Caughey
authors.affiliation: Department of Emergency Medicine, University of North Carolina Chapel Hill, 170 Manning Dr. CB#7594, Chapel Hill, NC, 27599, USA. Tim_Platts-Mills@med.unc.edu.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Platts-Mills
mesh_terms: D015982:Bias; D006801:Humans; D010380:Peer Review / Q000379:methods*; D011642:Publications; D016032:Randomized Controlled Trials as Topic; D012042:Registries / Q000592:standards*; D016896:Treatment Outcome