title: Prematurely ended phase III trials in Sweden during the years 2002-2008.
abstract: OBJECTIVE
  The aim of this study was to identify prematurely ended phase III clinical trials (CTs) and the proportion of such trials among all phase III CTs, review the reasons for the premature discontinuation of the CT, determine whether a data monitoring committee (DMC) was involved in this decision-making process, identify the data source on which the decision was based and review the consequences of the premature ending for product development. An additional aim was to identify risk factors for a premature ending.
  
  
  METHODS
  Prematurely ended phase III CTs in Sweden between 2002 and 2008 were identified by database searches. Identified trials were reviewed for treatment tested, study design, reasons for the premature ending, data source on which the decision was based and existence of and recommendation from a DMC. Three randomly selected but not prematurely ended control trials were identified, starting 1 May 2004, that were matched on the basis of application year.
  
  
  RESULTS
  A total of 84 phase III CT applications (8%) were prematurely ended during the study period. Most trials were ended due to safety and/or efficacy concerns. A DMC was more common among trials in which mortality was the primary endpoint and oncology trials. A recommendation from the DMC to terminate the trial was most likely in the case of combined safety- and efficacy-related issues arising from within the trial. Possible risk factors for a premature ending included mortality as an endpoint, obesity as an indication and a longer than planned study duration. Approximately 30% of prematurely ended trials with active substances that did not have a marketing authorization at the time of the clinical trial application resulted in the discontinuation of further development of the substance.
  
  
  CONCLUSIONS
  The DMCs in the phase III CTs reviewed here were used in accordance with guidelines. The use of DMCs was associated with possible risk factors for a premature ending and numerically, but not significantly associated with a premature ending.
authors.affiliation: Clinical Trial Unit, Medical Products Agency, P.O. Box 26, 751 03, Uppsala, Sweden. karin.hedenmalm@mpa.se
authors.forename: Karin
authors.initials: K
authors.lastname: Hedenmalm
authors.forename: Annika
authors.initials: A
authors.lastname: Johansson
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Bäckman
authors.forename: Patrik
authors.initials: P
authors.lastname: Ohagen
mesh_terms: D026661:Clinical Trials Data Monitoring Committees; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D003657:Decision Making; D057239:Early Termination of Clinical Trials / Q000706:statistics & numerical data*; D013548:Sweden