Observational studies of oseltamivir and influenza complications could suffer from residual confounding. Using negative control risk periods and a negative control outcome, we examined confounding control in a claims-based study of oseltamivir and influenza complications (pneumonia, all-cause hospitalization, antibiotic dispensing). Within the FDA's Sentinel System we identified individuals ≥18 years initiating oseltamivir on the influenza diagnosis date versus those who did not, during three influenza seasons (2014-2017). We evaluated primary outcomes in the following 1-30 days (primary risk period) and 61-90 days (negative control period), and non-vertebral fractures (negative control outcome) in days 1-30. We estimated propensity score-matched risk ratios (RR) per season. During 2014-15, oseltamivir was associated with a reduction in the risk of pneumonia (0.72, 95% CI 0.70, 0.75) and all-cause hospitalization (0.54, 95% CI 0.53, 0.55) in days 1-30. During days 61-90, estimates were near-null for pneumonia (1.04, 95% CI 0.95, 1.15) and hospitalization: (0.94, 95% CI 0.91, 0.98), but slightly increased for antibiotic dispensing (1.14, 95% CI 1.08, 1.21). The RR for fractures was near-null (1.09, 95% CI 0.99, 1.20). The 2016-17 estimates were comparable, while the 2015-16 season had conflicting results. Our study suggests minimal residual confounding for specific outcomes, but results differed by season.
Am J Epidemiol
Evaluating confounding control in estimations of influenza antiviral effectiveness in electronic health plan data.