27: Matched Design with Re-entry and Missingness for Comparative Effectiveness in Membranous Nephropathy

Music City Center 

Clinical trials comparing treatment effectiveness for rare diseases such as membranous nephropathy (MN) can be limited by short follow-up and small sample sizes. We demonstrate how a matched design combined with sequential re-entry and multiple imputation can be applied to observational data to generate reliable comparative effectiveness evidence while maximizing sample size. Individuals can have multiple eligible treatment initiations with this approach, and incomplete cases are retained. Propensity scores estimated with a GEE were used in 1:1 matching without replacement with hard matching on treatment history. Hazard ratios with robust confidence intervals that account for multilevel non-nested clustering were obtained in each imputed dataset and pooled. Restricted mean survival times with appropriate bootstrap confidence intervals were also pooled. An analog to per-protocol analysis censored individuals if they stopped adhering to treatment protocol and used inverse probability-of-censoring weights to address artificial censoring. Our application compared the long-term effectiveness of two immunosuppressants for MN, and results were consistent with a shorter 24-month trial.

comparative effectiveness

matching

sequential re-entry

multiple imputation

rare disease

robust variance estimation 

Section on Statistics in Epidemiology