Relative Vaccine Effectiveness of High-Dose versus Standard-Dose Influenza Vaccines among Veterans Health Administration Patients

Background: To examine whether a high-dose inactivated influenza vaccine was more efficacious in preventing hospitalizations than a standard-dose vaccine in the Veterans Health Administration (VHA) senior population. Methods: This study estimated the relative vaccine effectiveness (rVE) of high-dose versus standard-dose using a retrospective cohort of VHA patients 65 years of age or older in the 2015-16 influenza season. To adjust for measured confounders, we matched each high-dose recipient with up to four standard-dose recipients vaccinated at the same location within a two-week period and having two or more pre-existing medical co-morbidities. We used the previous event rate ratio method (PERR), a type of difference-in-differences analysis, to adjust for unmeasured confounders. Findings: We evaluated 104,965 standard-dose and 125,776 high-dose recipients; matching decreased the population to 49,091 standard-dose and 24,682 high-dose recipients. The matched, PERR-adjusted rVE was 25% (95% CI: 2-43%) against influenza- or pneumonia-associated hospitalization, 7% (95% CI: -2-14%) against all-cause hospitalization, 14% (95% CI: -8-32%) against influenza- or pneumonia-associated outpatient visit, 5% (95% CI: 2-8%) against all-cause outpatient visit, and 38% (95% CI: -5-65%) against laboratory-confirmed influenza. Interpretation: In protecting senior VHA patients against influenza- or pneumonia-associated hospitalization, a high-dose influenza vaccine is more effective than a standard-dose vaccine.