Abstract
IMPORTANCE: Prior drug safety studies investigating the risk of neuropsychiatric events (NPEs) after montelukast initiation have been limited by methodological issues, including incomplete confounder control and unmeasured outcomes associated with completeness of structured data, as well as events recorded only in unstructured clinical notes. OBJECTIVE: To examine the value associated with using linked claims and electronic health records (EHRs) (structured and unstructured data) while investigating the risk of any NPE among patients with asthma initiating montelukast compared with inhaled corticosteroids (ICSs). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used Oracle EHR Real-World Data linked to a national US claims dataset (July 1, 2015, to June 30, 2022) to identify patients aged 6 to 80 years with asthma newly initiating montelukast or ICSs. The data were analyzed between December 13, 2022, and August 2, 2024. MAIN OUTCOMES AND MEASURES: The primary outcome of any NPE and covariates was assessed using the incremental addition of each data source: analysis 1, claims-only data; analysis 2, claims plus structured EHR data; and analysis 3, claims plus structured and unstructured EHR data. Cox proportional hazard regression models using propensity score-matched cohorts across data sources were used to examine the risk of any NPE by treatment initiation group. RESULTS: Among 109 076 patients (mean [SD] age at treatment initiation, 28.8 [20.5] years, 59.4% female), 39 665 (36.4%) initiated montelukast and 69 411 (63.6%) ICSs. Incidence rates per 100 person-years of the first postindex NPE increased with additional data sources for both montelukast and ICS users (analysis 1, 17.11 [95% CI, 16.86-17.36] vs 15.57 [95% CI, 15.34-15.80], respectively; analysis 2, 19.10 [95% CI, 18.83-19.38] vs 18.23 [95% CI, 17.97-18.50], respectively; analysis 3, 27.78 [95% CI, 27.43-28.13] vs 27.40 [95% CI, 27.06-27.75], respectively). Hazard ratios were attenuated across contributing data sources for analysis 1 (1.08 [95% CI, 1.05-1.11]), analysis 2 (1.04 [95% CI, 1.01-1.06]), and analysis 3 (1.01 [95% CI, 1.00-1.03]). CONCLUSIONS AND RELEVANCE: This cohort study found that clinical information from linked claims and structured and unstructured EHR data was associated with enriched measurement of patient and disease characteristics and enhanced completeness of evidence vs claims data alone. The findings, however, did not differ substantially across the incrementally contributing data sources or from prior studies. Drug safety and effectiveness studies should integrate information using clinical notes from EHRs with consideration of potential limitations, challenges, and necessary validation processes.