title: Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.
abstract: OBJECTIVE
  To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials.
  
  
  METHODS
  Meta-epidemiological study.
  
  
  METHODS
  Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included.
  
  
  METHODS
  From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories).
  
  
  RESULTS
  50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57).
  
  
  CONCLUSIONS
  Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations.
authors.affiliation: Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, 06124 Perugia, Italy iosief_a@yahoo.it.
authors.forename: Iosief
authors.initials: I
authors.lastname: Abraha
authors.affiliation: Geriatrics and Geriatric Emergency Care, Italian National Research Centre on Aging Ancona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cherubini
authors.affiliation: Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, 06124 Perugia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cozzolino
authors.affiliation: General Medicine, Azienda USL Umbria 2, Terni, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Florio
authors.affiliation: General Medicine, Azienda USL Umbria 1, Perugia.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Luchetta
authors.affiliation: Geriatrics and Geriatric Emergency Care, Italian National Research Centre on Aging Ancona, Italy.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rimland
authors.affiliation: Department of Clinical and Experimental Medicine, University of Perugia, Perugia.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Folletti
authors.affiliation: Transfusion Medicine Service, Azienda Ospedaliera di Perugia, Perugia.
authors.forename: Mauro
authors.initials: M
authors.lastname: Marchesi
authors.affiliation: Transfusion Medicine Service, Azienda Ospedaliera di Perugia, Perugia.
authors.forename: Antonella
authors.initials: A
authors.lastname: Germani
authors.affiliation: Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, 06124 Perugia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Orso
authors.affiliation: Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, 06124 Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Eusebi
authors.affiliation: Health Planning Service, Regional Health Authority of Umbria, Department of Epidemiology, 06124 Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Montedori
mesh_terms: D015982:Bias; D016021:Epidemiologic Studies; D006801:Humans; D057194:Intention to Treat Analysis; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome