Approaches to inverse-probability-of-treatment–weighted estimation with concurrent treatments

Objectives: In a setting with two concurrent treatments, inverse-probability-of-treatment weights can be used to estimate the joint treatment effects or the marginal effect of one treatment while taking the other to be a confounder. We explore these two approaches in a study of intravenous iron use in hemodialysis patients treated concurrently with epoetin alfa (EPO). Study Design and Setting: We linked US Renal Data System data with electronic health records (2004–2008) from a large dialysis provider. Using a retrospective cohort design with 776,203 records from 117,050 regular hemodialysis patients, we examined a composite outcome: mortality, myocardial infarction, or stroke. Results: With EPO as a joint treatment, inverse-probability-of-treatment weights were unstable, confidence intervals for treatment effects were wide, covariate balance was unsatisfactory, and the treatment and outcome models were sensitive to omission of the baseline EPO covariate. By handling EPO exposure as a confounder instead of a joint treatment, we derived stable weights and balanced treatment groups on measured covariates. Conclusions: In settings with concurrent treatments, if only one treatment is of interest, then including the other in the treatment model as a confounder may result in more stable treatment effect estimates. Otherwise, extreme weights may necessitate additional analysis steps