title: Novel methods to deal with publication biases: secondary analysis of antidepressant trials in the FDA trial registry database and related journal publications.
abstract: OBJECTIVE
  To assess the performance of novel contour enhanced funnel plots and a regression based adjustment method to detect and adjust for publication biases.
  
  
  METHODS
  Secondary analysis of a published systematic literature review.
  
  
  METHODS
  Placebo controlled trials of antidepressants previously submitted to the US Food and Drug Administration (FDA) and matching journal publications.
  
  
  METHODS
  Publication biases were identified using novel contour enhanced funnel plots, a regression based adjustment method, Egger's test, and the trim and fill method. Results were compared with a meta-analysis of the gold standard data submitted to the FDA.
  
  
  RESULTS
  Severe asymmetry was observed in the contour enhanced funnel plot that appeared to be heavily influenced by the statistical significance of results, suggesting publication biases as the cause of the asymmetry. Applying the regression based adjustment method to the journal data produced a similar pooled effect to that observed by a meta-analysis of the FDA data. Contrasting journal and FDA results suggested that, in addition to other deviations from study protocol, switching from an intention to treat analysis to a per protocol one would contribute to the observed discrepancies between the journal and FDA results.
  
  
  CONCLUSIONS
  Novel contour enhanced funnel plots and a regression based adjustment method worked convincingly and might have an important part to play in combating publication biases.
authors: Department of Health Sciences, University of Leicester, Leicester LE1 7RH. sgm8@le.ac.uk
authors: Santiago G
authors: SG
authors: Moreno
authors: Alex J
authors: AJ
authors: Sutton
authors: Erick H
authors: EH
authors: Turner
authors: Keith R
authors: KR
authors: Abrams
authors: Nicola J
authors: NJ
authors: Cooper
authors: Tom M
authors: TM
authors: Palmer
authors: A E
authors: AE
authors: Ades
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic / Q000592:standards* / Q000706:statistics & numerical data; D012042:Registries; D012044:Regression Analysis; D013223:Statistics as Topic; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000928:Antidepressive Agents