title: Single-center trials show larger treatment effects than multicenter trials: evidence from a meta-epidemiologic study.
abstract: BACKGROUND
  A recent study suggested that results of single-center trials are frequently contradicted when similar trials are performed in multicenter settings.
  
  
  OBJECTIVE
  To perform a meta-epidemiologic study to evaluate whether estimates of treatment effect differ between single-center and multicenter randomized, controlled trials (RCTs).
  
  
  METHODS
  MEDLINE was searched via PubMed for meta-analyses of RCTs with binary outcomes that were published between August 2008 and January 2009 and in the first 6 months of 2010 in the 10 leading journals of each medical specialty. One issue of the Cochrane Database of Systematic Reviews was also searched.
  
  
  METHODS
  All individual RCTs included in the meta-analyses were selected.
  
  
  METHODS
  Data were extracted and their quality was assessed by use of the risk of bias tool of the Cochrane Collaboration.
  
  
  RESULTS
  The primary outcome was the ratio of odds ratios (ROR), used to quantify the difference in estimated intervention effect between single-center and multicenter RCTs. An ROR less than 1 would indicate larger estimates of the intervention effect in single-center trials. Sensitivity analyses were performed with adjustment for sample size, risk of bias within RCTs, and variance of the log odds ratio to take publication bias into account. Forty-eight meta-analyses were selected, including 421 RCTs (223 were single-center and 198 were multicenter). Single-center RCTs showed a larger intervention effect than did multicenter RCTs (combined ROR, 0.73 [95% CI, 0.64 to 0.83]), with low heterogeneity across individual meta-analyses (I(2) = 12.0%; P = 0.24). Adjustment for sample size yielded consistent results (ROR, 0.85 [CI, 0.74 to 0.97]), as did adjustment for risk of bias within RCTs, such as allocation concealment (ROR, 0.76 [CI, 0.67 to 0.86]), and variance of log odds ratio (ROR, 0.83 [CI, 0.72 to 0.96]).
  
  
  CONCLUSIONS
  Despite sensitivity analyses, meta-confounding cannot be fully excluded.
  
  
  CONCLUSIONS
  Single-center RCTs showed larger treatment effects than did multicenter RCTs, a finding that was consistent in all sensitivity analyses. These results suggest that this item should be considered when the results of RCTs and meta-analyses are interpreted.
  
  
  BACKGROUND
  Academic grant Recherche sur la Recherche from the Délégation Interrégionale à la Recherche Clinique (DIRC), Ile de France, Assistance Publique-Hôpitaux de Paris (APHP).
authors: U738 INSERM, Paris, France. agnes.dechartres@htd.aphp.fr
authors: Agnes
authors: A
authors: Dechartres
authors: Isabelle
authors: I
authors: Boutron
authors: Ludovic
authors: L
authors: Trinquart
authors: Pierre
authors: P
authors: Charles
authors: Philippe
authors: P
authors: Ravaud
mesh_terms: D015982:Bias; D015340:Epidemiologic Research Design; D006801:Humans; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic / Q000592:standards*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D018401:Sample Size; D012680:Sensitivity and Specificity; D016896:Treatment Outcome