title: Reanalyses of randomized clinical trial data.
abstract: OBJECTIVE
  Reanalyses of randomized clinical trial (RCT) data may help the scientific community assess the validity of reported trial results.
  
  
  OBJECTIVE
  To identify published reanalyses of RCT data, to characterize methodological and other differences between the original trial and reanalysis, to evaluate the independence of authors performing the reanalyses, and to assess whether the reanalysis changed interpretations from the original article about the types or numbers of patients who should be treated.
  
  
  METHODS
  We completed an electronic search of MEDLINE from inception to March 9, 2014, to identify all published studies that completed a reanalysis of individual patient data from previously published RCTs addressing the same hypothesis as the original RCT. Four data extractors independently screened articles and extracted data.
  
  
  METHODS
  Changes in direction and magnitude of treatment effect, statistical significance, and interpretation about the types or numbers of patients who should be treated.
  
  
  RESULTS
  We identified 37 eligible reanalyses in 36 published articles, 5 of which were performed by entirely independent authors (2 based on publicly available data and 2 on data that were provided on request; data availability was unclear for 1). Reanalyses differed most commonly in statistical or analytical approaches (n = 18) and in definitions or measurements of the outcome of interest (n = 12). Four reanalyses changed the direction and 2 changed the magnitude of treatment effect, whereas 4 led to changes in statistical significance of findings. Thirteen reanalyses (35%) led to interpretations different from that of the original article, 3 (8%) showing that different patients should be treated; 1 (3%), that fewer patients should be treated; and 9 (24%), that more patients should be treated.
  
  
  CONCLUSIONS
  A small number of reanalyses of RCTs have been published to date. Only a few were conducted by entirely independent authors. Thirty-five percent of published reanalyses led to changes in findings that implied conclusions different from those of the original article about the types and number of patients who should be treated.
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada3Department of Anesthesia, McMaster University4Depa.
authors.forename: Shanil
authors.initials: S
authors.lastname: Ebrahim
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada5Population Genomics Program, McMaster University.
authors.forename: Zahra N
authors.initials: ZN
authors.lastname: Sohani
authors.affiliation: University Health Network, Toronto, Ontario, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Montoya
authors.affiliation: Faculty of Health Sciences, McMaster University.
authors.forename: Arnav
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kristian
authors.initials: K
authors.lastname: Thorlund
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada8Faculty of Health Sciences, University of Ottawa.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California9Department of Health Research and Policy, Stanford University School of Medicine10Department of Statistics, Stanford University School of Humanities and.
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D003627:Data Interpretation, Statistical; D006801:Humans; D016032:Randomized Controlled Trials as Topic