title: Single-center trials tend to provide larger treatment effects than multicenter trials: a systematic review.
abstract: OBJECTIVE
  To assess whether the reported trial characteristics are associated with treatment effects on all-cause mortality within critical care medicine.
  
  
  METHODS
  We identified all eligible randomized controlled trials (RCTs) from Cochrane Reviews on patients with sepsis, septic shock, and cardiogenic shock. Risk of bias was judged on 12 trial characteristics, including the differentiation between single-center and multicenter trials. Hierarchical random-effects models quantified the impact of the risk of bias items on the reported effect estimates of mortality.
  
  
  RESULTS
  Twelve meta-analyses that involved 82 RCTs were selected and judged. Single-center trials estimated a significant larger treatment effect compared with multicenter trials (ratio of odds ratios, 0.64; 95% confidence interval: 0.47, 0.87). Treatment effect tended to be overestimated with selective reporting of preplanned end points. Biases in different trial characteristics are unlikely to operate independently and may have modified these associations.
  
  
  CONCLUSIONS
  The results of this study highlight a substantial difference in treatment effect estimates between single-center and multicenter trials. Therefore, we recommend that results from single-center trials should be cautiously used for decision making.
authors: Institute of Medical Epidemiology, Biostatistics and Informatics, Martin Luther University of Halle-Wittenberg, 06097 Halle (Saale), Germany. Electronic address: susanne.unverzagt@medizin.uni-halle.de.
authors: Susanne
authors: S
authors: Unverzagt
authors: Roland
authors: R
authors: Prondzinsky
authors: Frank
authors: F
authors: Peinemann
mesh_terms: D015982:Bias; D003422:Critical Care; D006801:Humans; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012196:Review Literature as Topic; D012306:Risk; D018805:Sepsis / Q000401:mortality / Q000628:therapy*; D012770:Shock, Cardiogenic / Q000401:mortality / Q000628:therapy*; D012772:Shock, Septic / Q000401:mortality / Q000628:therapy; D016896:Treatment Outcome
keywords: Confounding factors; Critical care medicine; Randomized controlled trials; Research design; Risk of bias