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Publication Briefs

Study Compares High-Dose Influenza Vaccine to Standard-Dose Vaccine among Elderly Veterans

While vaccination remains the most effective approach for preventing influenza-related hospitalizations and death, the effectiveness of influenza vaccination among elderly persons is poor. A new high-dose (HD) vaccine received FDA accelerated approval in December 2009 based on its superior ability to provoke an immune response compared to standard-dose (SD) vaccine. However, the CDC and the Advisory Committee on Immunization Practices continue to not state a preference for either HD or SD vaccine for elderly persons. Consequently, there is no formal guidance and few published data on clinical outcomes to support decisions about which vaccine to recommend for this vulnerable patient population. Therefore, this retrospective cohort study assessed the relative effectiveness of HD influenza vaccination compared to SD vaccination among 25,714 elderly Veterans (65 years and older) who received HD vaccine and 139,511 elderly Veterans who received SD vaccine in 23 VAMCs during the 2010-2011 flu season. The primary outcome was hospitalization for pneumonia or influenza. Investigators also examined hospitalization for any cause – and death by any cause – as secondary outcomes. Patient demographics and comorbid illnesses, particularly HIV, also were examined.


  • High-dose influenza vaccine was not more effective than standard-dose vaccine in protecting against hospitalization for influenza or pneumonia in Veterans ≥ 65 years of age; however, subgroup analysis found that it was more effective in Veterans ≥85 years of age.
  • The rate of hospitalization for influenza or pneumonia was 0.3% for Veterans in both the HD and SD groups during the influenza season.
  • There were no significant differences in all-cause hospitalization and mortality between Veterans in the HD and SD groups.
  • Compared to Veterans who received the SD vaccine, those who received the HD vaccine were slightly older, more likely to be African-American, had a higher comorbidity score, and were more likely to have HIV and exposure to immunosuppressive drugs.


  • Since data on patients admitted to a VA hospital did not include results of laboratory confirmation for influenza infection, the primary hospitalization outcome may have identified Veterans with respiratory conditions that were not influenza related, and/or missed Veterans admitted with influenza but not coded as having influenza or pneumonia.
  • This study was observational and treatment allocation was not randomized, so the potential for residual confounding by indication or confounding by unmeasured covariates cannot be eliminated.
  • Veterans older than age 65 are eligible for Medicare, and may have received healthcare services, including hospitalization, outside of VA.

This study was partly funded by HSR&D. Dr. Richardson, Ms. Medvedeva, and Mr. Roberts are part of HSR&D's Center for Health Equity Research and Promotion in Philadelphia, PA.

PubMed Logo Richardson D, Medvedeva E, Roberts C, and Linkin D. Comparative Effectiveness of High-Dose versus Standard-Dose Influenza Vaccination in Community-Dwelling Veterans. Clinical Infectious Diseases. March 31, 2015; Epub ahead of print.

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