Objectives
Adjustment for center in multicenter trials is recommended when there are between-center differences or when randomization has been stratified by center. However, common methods of analysis (such as fixed-effects, Mantel-Haenszel, or stratified Cox models) often require a large number of patients or events per center to perform well.
Study design and setting
We reviewed 206 multicenter randomized trials published in four general medical journals to assess the average number of patients and events per centre, and determine whether appropriate methods of analysis were used in trials with few patients or events per centre.
Results
The median number of events per center/treatment arm combination for trials using a binary or survival outcome was 3 (IQR 1–10). Sixteen percent of trials had less than 1 event per center/treatment combination, 50% fewer than 3, and 63% fewer than 5. Of the trials which adjusted for center using a method of analysis which requires a large number of events per center, 6% had less than 1 event per center-treatment combination, 25% fewer than 3, and 50% fewer than 5. Methods of analysis which allow for few events per center, such as random-effects models or GEEs, were rarely used.
Conclusions
Many multicenter trials contain few events per center. Adjustment for center using randomeffects models or GEE with model-based (non-robust) standard-errors may be beneficial in these scenarios.