title: Modified intention-to-treat analysis did not bias trial results.
abstract: OBJECTIVE
  To investigate whether analysis of the modified intention-to-treat (mITT) population with postrandomization exclusion of patients from analysis is associated with biased estimates of treatment effect compared to the conservative intention-to-treat (ITT) population.
  
  
  METHODS
  Placebo-controlled, blinded randomized trials on biological or targeted interventions for rheumatoid arthritis were identified through a systematic search. Two authors independently extracted data. A random-effects meta-analysis was used to combine odds ratios as an expression of treatment effect and stratify according to the different analysis populations.
  
  
  RESULTS
  Seventy-two randomized trials were included and analyzed (23,842 patients). Thirty trials analyzed the ITT population, 37 analyzed an mITT population, and 5 trials had an unclear analysis population. The treatment effect of active intervention compared to control, when based on mITT, was comparable to ITT (odds ratio 3.76 [95% confidence interval 3.09, 4.57], and 3.47 [2.77, 4.34]; comparison P = 0.60).
  
  
  CONCLUSIONS
  We found no difference in the treatment effect between randomized trials using ITT and mITT analyses populations. This suggests that the mITT approach in rheumatoid arthritis trials investigating biological or targeted interventions does not introduce bias compared to ITT.
authors.affiliation: Department of Rheumatology, Musculoskeletal Statistics Unit, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Dossing
authors.affiliation: Department of Rheumatology, Musculoskeletal Statistics Unit, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Tarp
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Clinical Epidemiology Program, Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute, University of Ottawa, Room 3105, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: Department of Rheumatology, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark.
authors.forename: Bjarke B
authors.initials: BB
authors.lastname: Hansen
authors.affiliation: Department of Rheumatology, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bliddal
authors.affiliation: Department of Rheumatology, Musculoskeletal Statistics Unit, The Parker Institute, Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Copenhagen, Denmark. Electronic address: Robin.Christensen@regionh.dk.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D015982:Bias; D016001:Confidence Intervals; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis / Q000379:methods*; D008297:Male; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic
chemical_list: D018501:Antirheumatic Agents
keywords: Bias; Biological disease-modifying antirheumatic drugs (DMARD); Epidemiology; Intention-to-treat analysis; Meta-analysis; Rheumatoid arthritis