title: Constraint-induced movement therapy: trial sequential analysis applied to Cochrane collaboration systematic review results.
abstract: BACKGROUND
  Trial sequential analysis (TSA) may establish when firm evidence about the efficacy of interventions is reached in a cumulative meta-analysis, combining a required information size with adjusted thresholds for conservative statistical significance. Our aim was to demonstrate TSA results on randomized controlled trials (RCTs) included in a Cochrane systematic review on the effectiveness of constraint-induced movement therapy (CIMT) for stroke patients.
  
  
  METHODS
  We extracted data on the functional independence measure (FIM) and the action research arm test (ARAT) from RCTs that compared CIMT versus other rehabilitative techniques. Mean differences (MD) were analyzed using a random-effects model. We calculated the information size and the cumulative Z-statistic, applying the O'Brien-Fleming monitoring boundaries.
  
  
  RESULTS
  We included data from 14 RCTs. In the conventional meta-analysis (seven trials, 233 patients), the effect of CIMT on FIM was reported as significant (MD 2.88, 95% CI 0.08 to 5.68; P = 0.04). The diversity-adjusted required information size was 142 patients, and the cumulative Z-score did not cross the trial sequential monitoring boundary for benefit (adjusted 95% CI -0.02 to 5.78). The effect of CIMT on ARAT (nine trials, 199 patients) was reported as significant (MD 7.78, 95% CI 1.19 to 14.37; P = 0.02). However, the diversity-adjusted required information size was 252 patients, and the Z-score did not cross the trial sequential monitoring boundary for benefit (adjusted 95% CI -0.06 to 15.62).
  
  
  CONCLUSIONS
  Although conventional meta-analyses of CIMT reached statistical significance, their overall results remain inconclusive and might be spurious. Researchers should not be overconfident on CIMT efficacy based on the results of meta-analyses and derived recommendations.
authors.affiliation: Health Professional Science of Rehabilitation, University of Milan, Via Festa del Perdono, 7, 20122 Milan, Italy. gre.caste@gmail.com.
authors.forename: Greta
authors.initials: G
authors.lastname: Castellini
authors.forename: Silvia
authors.initials: S
authors.lastname: Gianola
authors.forename: Rita
authors.initials: R
authors.lastname: Banzi
authors.forename: Davide
authors.initials: D
authors.lastname: Corbetta
authors.forename: Roberto
authors.initials: R
authors.lastname: Gatti
authors.forename: Valeria
authors.initials: V
authors.lastname: Sirtori
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
mesh_terms: D016009:Chi-Square Distribution; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D019317:Evidence-Based Medicine / Q000706:statistics & numerical data; D005081:Exercise Therapy / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D009043:Motor Activity; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D015203:Reproducibility of Results; D012107:Research Design; D020521:Stroke / Q000175:diagnosis / Q000503:physiopathology; D000071939:Stroke Rehabilitation; D013997:Time Factors; D016896:Treatment Outcome