Investigation of 2‐stage meta‐analysis methods for joint longitudinal and time‐to‐event data through simulation and real data application

BACKGROUND:Joint modeling of longitudinal and time-to-event data is often advantageous over separate longitudinal or time-to-event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time-to-event outcomes. The current literature on joint modeling focuses mainly on the analysis of single studies with a lack of methods available for the meta-analysis of joint data from multiple studies. METHODS:We investigate a variety of one-stage methods for the meta-analysis of joint longitudinal and time-to-event outcome data. These methods are applied to the INDANA dataset to investigate longitudinally measured systolic blood pressure, with each of time to death, time to myocardial infarction, and time to stroke. Results are compared to separate longitudinal or time-to-event meta-analyses. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. RESULTS:The performance of the examined one-stage joint meta-analytic models varied. Models that accounted for between study heterogeneity performed better than models that ignored it. Of the examined methods to account for between study heterogeneity, under the examined association structure, fixed effect approaches appeared preferable, whereas methods involving a baseline hazard stratified by study were least time intensive. CONCLUSIONS:One-stage joint meta-analytic models that accounted for between study heterogeneity using a mix of fixed effects or a stratified baseline hazard were reliable; however, models examined that included study level random effects in the association structure were less reliable.