Single-center trials tend to provide larger treatment effects than multicenter trials: a systematic review

Abstract

Objectives: To assess whether the reported trial characteristics are associated with treatment effects on all-cause mortality within critical care medicine.

Study design and setting: 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.

Conclusion: 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.

Keywords: Confounding factors; Critical care medicine; Randomized controlled trials; Research design; Risk of bias.