title: Randomised controlled trials in oncology closed early for benefit: trends in methodology, results, and interpretation.
abstract: OBJECTIVE
  To assess methodology, results and interpretation of oncology randomised controlled trials closed early for benefit (RCTCEB).
  
  
  METHODS
  Structured literature search (1950-2008) to identify all published oncology RCTCEB. We then searched for related follow-up articles and conference abstracts to evaluate whether study results and conclusions changed with longer follow-up. A standardised data abstraction process captured information related to statistical methodology, details of interim analyses, results and conclusions. Original articles and follow-up reports were compared for results of primary end-point and author conclusions.
  
  
  RESULTS
  We identified 71 RCTCEB. In 16 articles (23%) the study primary end-point was not explicitly stated. Most trials were open to accrual (47/71, 66%) at the time of closure. Formal interim analysis was performed in 65 (92%) trials of which 72% (47/65) was reported as planned; 82% (53/65) reported stopping rules. Trials on average accrued 75% of the planned sample size. Amongst the 23 (32%) RCTCEB with follow-up reports, in only one case did the study results or conclusions change substantially.
  
  
  CONCLUSIONS
  While the majority of oncology RCTCEB follows rigourous methodological principles, an important percentage includes limitations in design and/or analysis. Amongst the 23 studies with subsequent follow-up reports, initial results were confirmed in 22 (96%).
authors.affiliation: NCIC Clinical Trials Group and Queen's University Cancer Research Institute, Kingston, Canada. boothc@kgh.kari.net
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Booth
authors.forename: Pavlo
authors.initials: P
authors.lastname: Ohorodnyk
authors.forename: Liting
authors.initials: L
authors.lastname: Zhu
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Meyer
mesh_terms: D003627:Data Interpretation, Statistical; D057239:Early Termination of Clinical Trials / Q000379:methods / Q000706:statistics & numerical data / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data / Q000639:trends