title: Comparison of results from different imputation techniques for missing data from an anti-obesity drug trial.
abstract: BACKGROUND
  In randomised trials of medical interventions, the most reliable analysis follows the intention-to-treat (ITT) principle. However, the ITT analysis requires that missing outcome data have to be imputed. Different imputation techniques may give different results and some may lead to bias. In anti-obesity drug trials, many data are usually missing, and the most used imputation method is last observation carried forward (LOCF). LOCF is generally considered conservative, but there are more reliable methods such as multiple imputation (MI).
  
  
  OBJECTIVE
  To compare four different methods of handling missing data in a 60-week placebo controlled anti-obesity drug trial on topiramate.
  
  
  METHODS
  We compared an analysis of complete cases with datasets where missing body weight measurements had been replaced using three different imputation methods: LOCF, baseline carried forward (BOCF) and MI.
  
  
  RESULTS
  561 participants were randomised. Compared to placebo, there was a significantly greater weight loss with topiramate in all analyses: 9.5 kg (SE 1.17) in the complete case analysis (N = 86), 6.8 kg (SE 0.66) using LOCF (N = 561), 6.4 kg (SE 0.90) using MI (N = 561) and 1.5 kg (SE 0.28) using BOCF (N = 561).
  
  
  CONCLUSIONS
  The different imputation methods gave very different results. Contrary to widely stated claims, LOCF did not produce a conservative (i.e., lower) efficacy estimate compared to MI. Also, LOCF had a lower SE than MI.
authors.affiliation: The Nordic Cochrane Centre, Dept 7811, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Anders W
authors.initials: AW
authors.lastname: Jørgensen
authors.affiliation: Copenhagen Trial Unit, Copenhagen Centre of Clinical Intervention Research, Dept 7812, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lundstrøm
authors.affiliation: Copenhagen Trial Unit, Copenhagen Centre of Clinical Intervention Research, Dept 7812, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.affiliation: The Nordic Cochrane Centre, Dept 7811, Rigshospitalet, Copenhagen, Denmark; Institute of Medicine and Surgery, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Gøtzsche
mesh_terms: D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001835:Body Weight; D003627:Data Interpretation, Statistical; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D019440:Anti-Obesity Agents; D000077236:Topiramate; D005632:Fructose