Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis

Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models.The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables.Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification.Using observational data to compare outcomes associated with different treatments may result in biased estimates because of non-random treatment assignment. To correct for variables that may confound an association, the traditional approach is to apply multivariable-adjusted modeling, but in recent years, use of propensity scores has become increasingly popular [1]. The concept of a multivariate confounder score was first introduced by Miettinen in 1976 [2], but the formal concept of propensity scores to estimate causal effects in observational studies was first described by Rosenbaum and Rubin [3]. A propensity score is a conditional prob