Cluster-weighted modified Poisson regression for estimating risk ratios in longitudinal data with informative cluster sizes

Variation in binary outcomes over time by cluster size arises across various biomedical disciplines, including reproductive health, dental medicine, and psychiatric epidemiology. This study formally integrates modified Poisson regression with cluster-weighted generalized estimating equations (MP-CWGEE) for computing risk ratios in longitudinal studies with informative cluster sizes. Using a comprehensive Monte-Carlo simulation study, we empirically evaluated MP-CWGEE’s statistical properties against alternative modeling approaches: MP-GEE, log-binomial CWGEE (LB-CWGEE), and log-binomial GEE (LB-GEE). We conducted 1,000 simulations across varying sample sizes, risk ratios, and informativeness degrees. MP-CWGEE demonstrated superior performance in model convergence, empirical bias, average estimated standard error, coverage, and Type 1 error control. While LB-CWGEE showed comparable results, its convergence rates were slightly inferior. The benefits of cluster-weighted models (MP-CWGEE and LB-CWGEE) over unweighted models (MP-GEE and LB-GEE) were pronounced in scenarios with informative cluster sizes. We demonstrated MP-CWGEE’s practical application to a cohort study of people who used illicit opioids in New York City. We also provided implementation code for R, Stata, and SAS to facilitate wider adoption of the MP-CWGEE approach.