An overview of methods and empirical comparison of aggregate data and individual patient data results for investigating heterogeneity in meta-analysis of time-to-event outcomes

Combining the results of individual studies using meta-analysis may be undertaken using either aggregate data (AD) or individual patient data (IPD). In any meta-analysis it is important to consider statistical heterogeneity between studies. Potential sources of heterogeneity can be explored using regression models with either AD or IPD. An overview of approaches and empirical assessment of how the results and conclusions differ from these analyses is undertaken using a meta-analysis of five randomized controlled trials comparing two antiepileptic drugs with time-to-event outcomes. Alternative meta-regression models using AD are compared to stratified Cox regression models using IPD. Age as a potential cause of heterogeneity is detected by both AD and IPD regression models. Time from first ever seizure to randomization is only identified by some AD models. A more thorough explanation of heterogeneity is obtained from the model using IPD but further empirical evidence comparing IPD and AD results are needed.