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Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses
Paul E Alexander1, Ashley J Bonner2, Arnav Agarwal3
1Health Research Methods (HRM), Department of Clinical Epidemiology and Biostatistics, McMaster University, Health Sciences Building (HSB), 1280 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Journal of Clinical Epidemiology
|November 25, 2015
Summary
Single-center trials do not show larger effects than multi-center trials for binary outcomes. However, single-center trials yield slightly larger effect sizes for continuous outcomes, warranting consideration in systematic reviews.
Area of Science:
- Clinical Research Methodology
- Meta-Analysis and Epidemiology
Background:
- Prior research on whether single-center trials yield larger estimates than multi-center trials has produced conflicting results.
- This study addresses the need for a systematic examination of effect size differences between single-center and multi-center randomized controlled trials.
Purpose of the Study:
- To investigate the extent to which single-center trials systematically produce larger effect estimates compared to multi-center trials.
- To analyze differences in effect sizes for both binary and continuous outcomes.
Main Methods:
- A meta-epidemiologic study was conducted using meta-analyses (MAs) of randomized controlled trials (RCTs) published in 2012.
- Data from 119 core clinical journals and the Cochrane Database of Systematic Reviews were analyzed.
- Pooled ratio of odds ratios (RORs) for binary variables and standardized mean differences (SMDs) for continuous outcomes were computed using random-effects meta-regression and meta-analysis modeling.
Main Results:
- Analysis of 25 MAs with binary outcomes (241 RCTs) revealed no significant difference in effect magnitude between single-center (SC) and multi-center (MC) trials (ROR: 1.02; 95% CI: 0.83, 1.24).
- Analysis of 18 MAs with continuous outcomes (173 RCTs) showed systematically larger effect sizes in SC compared to MC trials (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05).
Conclusions:
- The findings do not support previous claims of larger effects in SC trials for binary outcomes.
- A small but consistent increase in effect size was observed for SC trials compared to MC trials in continuous outcomes.
- Systematic reviews should consider including all trials regardless of center design and explore single-center vs. multi-center status as a source of heterogeneity.
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