title: Placebo response rate in clinical trials of fistulizing Crohn's disease: systematic review and meta-analysis.
abstract: OBJECTIVE
  It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD.
  
  
  METHODS
  We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined.
  
  
  RESULTS
  Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%-20.9%), with significant heterogeneity (I(2) = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%-22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect.
  
  
  CONCLUSIONS
  In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo.
authors.affiliation: Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom. Electronic address: alexf12399@yahoo.com.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Ford
authors.affiliation: Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom.
authors.forename: Pavit
authors.initials: P
authors.lastname: Luthra
authors.affiliation: Digestive Health Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hanauer
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Travis
authors.affiliation: Georgetown University School of Medicine, Washington, District of Columbia.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Harris
authors.affiliation: Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
mesh_terms: D003424:Crohn Disease / Q000150:complications* / Q000188:drug therapy*; D005402:Fistula / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic
chemical_list: D010919:Placebos
keywords: Fistula; IBD; Meta-analysis; Placebo Effect; Randomized Controlled Trials