Comparing New-User Cohort Designs: The Example of Proton Pump Inhibitor Effectiveness in Idiopathic Pulmonary Fibrosis.

Abstract

The prevalent new-user cohort design is useful for assessing the effectiveness of a medication in the absence of an active comparator. Alternative approaches, particularly in the presence of informative censoring, include a variant of this design based on never users of the study drug and the marginal structural Cox model approach. We compared these approaches in assessing the effectiveness of proton pump inhibitors (PPIs) in reducing mortality among patients with idiopathic pulmonary fibrosis (IPF) using a cohort of IPF patients identified in the United Kingdom's Clinical Practice Research Datalink and diagnosed between 2003 and 2016. The cohort included 2,944 IPF patients, 1,916 of whom initiated use of PPIs during follow-up. There were 2,136 deaths (mortality rate = 25.8 per 100 person-years). Using the conventional prevalent new-user design, we found a hazard ratio for death associated with PPI use compared with nonuse of 1.07 (95% confidence interval (CI): 0.94, 1.22). The variant of the prevalent new-user design comparing PPI users with never users found a hazard ratio of 0.82 (95% CI: 0.73, 0.91), while the marginal structural Cox model found a hazard ratio of 1.08 (95% CI: 0.85, 1.38). The marginal structural model and the conventional prevalent new-user design, both accounting for informative censoring, produced similar results. However, the prevalent new-user design variant based on never users introduced selection bias and should be avoided.