title: Handling missing data in RCTs; a review of the top medical journals.
abstract: BACKGROUND
  Missing outcome data is a threat to the validity of treatment effect estimates in randomized controlled trials. We aimed to evaluate the extent, handling, and sensitivity analysis of missing data and intention-to-treat (ITT) analysis of randomized controlled trials (RCTs) in top tier medical journals, and compare our findings with previous reviews related to missing data and ITT in RCTs.
  
  
  METHODS
  Review of RCTs published between July and December 2013 in the BMJ, JAMA, Lancet, and New England Journal of Medicine, excluding cluster randomized trials and trials whose primary outcome was survival.
  
  
  RESULTS
  Of the 77 identified eligible articles, 73 (95%) reported some missing outcome data. The median percentage of participants with a missing outcome was 9% (range 0 - 70%). The most commonly used method to handle missing data in the primary analysis was complete case analysis (33, 45%), while 20 (27%) performed simple imputation, 15 (19%) used model based methods, and 6 (8%) used multiple imputation. 27 (35%) trials with missing data reported a sensitivity analysis. However, most did not alter the assumptions of missing data from the primary analysis. Reports of ITT or modified ITT were found in 52 (85%) trials, with 21 (40%) of them including all randomized participants. A comparison to a review of trials reported in 2001 showed that missing data rates and approaches are similar, but the use of the term ITT has increased, as has the report of sensitivity analysis.
  
  
  CONCLUSIONS
  Missing outcome data continues to be a common problem in RCTs. Definitions of the ITT approach remain inconsistent across trials. A large gap is apparent between statistical methods research related to missing data and use of these methods in application settings, including RCTs in top medical journals.
authors.affiliation: Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA. melaniebell@email.arizona.edu.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Bell
authors.forename: Mallorie
authors.initials: M
authors.lastname: Fiero
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Horton
authors.forename: Chiu-Hsieh
authors.initials: CH
authors.lastname: Hsu
mesh_terms: D006801:Humans; D057194:Intention to Treat Analysis; D011643:Publishing; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome