03 Apr High-Dose Flu Vaccine Prevented More Influenza Infections In Elderly Than Standard Dose
MedicalResearch.com Interview with:
Dr Richard Forshee PhD
Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research
U.S. Food and Drug Administration
Silver Spring, MD
On behalf of the study authors
Medical Research: What is the background for this study? What are the main findings?
Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken. The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group. The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients.
In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness. This pathway reduces the time it takes for needed medical products to become available to the public. Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease.
As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease.
A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older. The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose.
Additional background about this study: “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” is available at:
A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at:
Medical Research: What should clinicians and patients take away from your report?
Dr. Forshee: The scientists found that the high-dose influenza vaccine was 22% more effective at preventing influenza-associated illness than standard-dose vaccine among individuals ages 65 years and older. They also found a similar effect for the more serious outcome of influenza-associated hospital admissions and emergency department visits in this age group.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Forshee: The results of this study were consistent with relative efficacy estimates reported in the manufacturer’s research, “Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults,” and demonstrated that this study design could be used in the future to estimate the benefits of newer influenza vaccines. The methods may also be used to study more rare events, such as hospitalizations. In addition, future studies based on this design could also enable rapid evaluation of the life-saving effectiveness of other vaccines, including those protecting against pandemics.
Further information about the manufacturer’s study is available at:
MedicalResearch.com Interview with: Dr Richard Forshee PhD (2015). High-Dose Flu Vaccine Prevented More Influenza Infections In Elderly