title: Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms.
  
  
  METHODS
  A systematic review and meta-analysis.
  
  
  METHODS
  We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014.
  
  
  RESULTS
  Effect sizes (ES) in the active and placebo arms in the trials' primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered.
  
  
  RESULTS
  We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R(2) of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration.
  
  
  CONCLUSIONS
  The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated.
authors: Fram Rehabilitation Centre, Bærum, Norway.
authors: Robin
authors: http://orcid.org/0000-0002-8436-4519
authors: R
authors: Holtedahl
authors: Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway.
authors: Jens Ivar
authors: JI
authors: Brox
authors: South-Eastern Norway Regional Health Authority, Hamar, Norway.
authors: Ole
authors: O
authors: Tjomsland
mesh_terms: D006348:Cardiac Surgical Procedures; D006801:Humans; D019060:Minimally Invasive Surgical Procedures; D019635:Neurosurgical Procedures; D015990:Placebo Effect; D012107:Research Design; D016896:Treatment Outcome
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