title: Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis.
abstract: BACKGROUND
  A high-dose trivalent inactivated influenza vaccine was licensed in 2009 by the US Food and Drug Administration (FDA) on the basis of serological criteria. We sought to establish whether high-dose inactivated influenza vaccine was more effective for prevention of influenza-related visits and hospital admissions in US Medicare beneficiaries than was standard-dose inactivated influenza vaccine.
  
  
  METHODS
  In this retrospective cohort study, we identified Medicare beneficiaries aged 65 years and older who received high-dose or standard-dose inactivated influenza vaccines from community pharmacies that offered both vaccines during the 2012-13 influenza season. Outcomes were defined with billing codes on Medicare claims. The primary outcome was probable influenza infection, defined by receipt of a rapid influenza test followed by dispensing of the neuraminidase inhibitor oseltamivir. The secondary outcome was a hospital or emergency department visit, listing a Medicare billing code for influenza. We estimated relative vaccine effectiveness by comparing outcome rates in Medicare beneficiaries during periods of high influenza circulation. Univariate and multivariate Poisson regression models were used for analyses.
  
  
  RESULTS
  Between Aug 1, 2012 and Jan 31, 2013, we studied 929,730 recipients of high-dose vaccine and 1,615,545 recipients of standard-dose vaccine. Participants enrolled in each cohort were well balanced with respect to age and presence of underlying medical disorders. The high-dose vaccine (1·30 outcomes per 10,000 person-weeks) was 22% (95% CI 15-29) more effective than the standard-dose vaccine (1·01 outcomes per 10,000 person-weeks) for prevention of probable influenza infections (rapid influenza test followed by oseltamivir treatment) and 22% (95% CI 16-27%) more effective for prevention of influenza hospital admissions (0·86 outcomes per 10,000 person-weeks in the high-dose cohort vs 1·10 outcomes per 10,000 person-weeks in the standard-dose cohort).
  
  
  CONCLUSIONS
  Our retrospective cohort study in US Medicare beneficiaries shows that, in people 65 years of age and older, high-dose inactivated influenza vaccine was significantly more effective than standard-dose vaccine in prevention of influenza-related medical encounters. Additionally, the large population in our study enabled us to show, for the first time, a significant reduction in influenza-related hospital admissions in high-dose compared to standard-dose vaccine recipients, an outcome not shown in randomised studies. These results provide important new information to be considered by policy makers recommending influenza vaccinations for elderly people.
  
  
  BACKGROUND
  FDA and the office of the Assistant Secretary of Planning and Evaluation.
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Hector S
authors: HS
authors: Izurieta
authors: Acumen LLC, Burlingame, CA, USA.
authors: Nicole
authors: N
authors: Thadani
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: David K
authors: DK
authors: Shay
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Yun
authors: Y
authors: Lu
authors: Acumen LLC, Burlingame, CA, USA.
authors: Aaron
authors: A
authors: Maurer
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA; Battelle, Atlanta, GA, USA.
authors: Ivo M
authors: IM
authors: Foppa
authors: Acumen LLC, Burlingame, CA, USA.
authors: Riley
authors: R
authors: Franks
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Douglas
authors: D
authors: Pratt
authors: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Electronic address: richard.forshee@fda.hhs.gov.
authors: Richard A
authors: RA
authors: Forshee
authors: Acumen LLC, Burlingame, CA, USA.
authors: Thomas
authors: T
authors: MaCurdy
authors: Centers for Medicare and Medicaid Services, Washington, DC, USA.
authors: Chris
authors: C
authors: Worrall
authors: Acumen LLC, Burlingame, CA, USA.
authors: Andrew E
authors: AE
authors: Howery
authors: Centers for Medicare and Medicaid Services, Washington, DC, USA.
authors: Jeffrey
authors: J
authors: Kelman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004632:Emergency Medical Services / Q000706:statistics & numerical data; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D006278:Medicare; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated