Objectives: Inverse probability of treatment weighting (IPTW) has been used in observational studies to reduce selection bias. For estimates of the main effects to be obtained, a pseudo data set is created by weighting each subject by IPTW and analyzed with conventional regression models. Currently, variance estimation requires additional work depending on type of outcomes. Our goal is to demonstrate a statistical approach to directly obtain appropriate estimates of variance of the main effects in regression models.

Methods: We carried out theoretical and simulation studies to show that the variance of the main effects estimated directly from regressions using IPTW is underestimated and that the type I error rate is higher because of the inflated sample size in the pseudo data. The robust variance estimator using IPTW often slightly overestimates the variance of the main effects. We propose to use the stabilized weights to directly estimate both the main effect and its variance from conventional regression models.

Results: We applied the approach to a study examining the effectiveness of serum potassium monitoring in reducing hyperkalemia-associated adverse events among 27,355 diabetic patients newly prescribed with a renin-angiotensin-aldosterone system inhibitor. The incidence rate ratio (with monitoring vs. without monitoring) and confidence intervals were 0.46 (0.34, 0.61) using the stabilized weights compared with 0.46 (0.38, 0.55) using typical IPTW.

Conclusions: Our theoretical, simulation results and real data example demonstrate that the use of the stabilized weights in the pseudo data preserves the sample size of the original data, produces appropriate estimation of the variance of main effect, and maintains an appropriate type I error rate.