VA Research: High-Dose Flu Vaccine Reduces Hospitalizations, Saves Money

by Annette Boyle

September 22, 2019

But It’s Not Offered by the VA This Year

WHITE RIVER JUNCTION, VT—The high-dose influenza vaccine is more effective and less expensive for the VA than the standard dose vaccine for veterans over age 65, new research showed.

That’s according to a pair of studies from the journal Vaccine.

In fact, VA researchers pointed out that the savings were quite healthy: $202 per vaccinated recipient, adding that most of the cost savings comes from reducing the number of acute cardio-respiratory disease-related hospitalizations among veterans over age 65.

Despite the demonstrated effectiveness, however, questions remain as to whether and when the VA nor DoD will offer the high-dose vaccine as covered options for the upcoming influenza season.

Number of influenza vaccinations, hospitalization rates for cardio-respiratory disease, and number needed to treat (NNT) to prevent one hospitalization for VHA enrollees vaccinated during respiratory seasons 2010–11 through 2014–15.

With 4.4% of the vaccinated veteran population over age 65 receiving the high-dose vaccine instead of the standard dose from the 2010/2011 flu season through the 2014/2015 flu season, the authors estimated that the VA saved $32 million in direct hospitalization costs compared to all veterans receiving the standard dose. If 10% of older veterans had received the high-dose vaccine, the VA could have reduced its costs by $74 million over the five flu seasons.1,2

Mean cost and reimbursement per hospitalization for cardio-respiratory disease and vaccination among vaccinated VHA enrollees during the 2010–11 through 2014–15 respiratory seasons in US dollars.

“The high-dose vaccine is only recommended for use in individuals over age 65,” said Ellyn Russo, MD, director of the VA’s clinical epidemiology program and an author of one of the studies. “There is no preferential recommendation. It depends on what the VA has purchased or has on formulary that year.”

That stance mirrors the national Centers for Disease Prevention and Control position, which last year stated “no preference is expressed for any influenza vaccine over another.” More specifically, “the CDC and its Advisory Committee on Immunization Practices have not expressed a preference for any flu vaccine indicated for people 65 and older.” The CDC has not updated the recommendations for 2019/2020.

Among older veterans, for whom the VA has good influenza vaccination data, “we saw an increase from 3% receiving the high-dose vaccine in 2010/2011 to 8% in 2014/2015,” Russo told U.S. Medicine. “Studying more recent seasons, it’s probably still under 10%, but we have seen an increase.” Overall, about 70% of older veterans receive a flu shot annually.

The upward trend appears unlikely to continue through this year, however. Typically, the VA leaves vaccination programs and selection up to each individual institutions or medical center, Russo noted.

Not Offered This Year

In a switch, the VA announced that it is not offering the high-dose vaccine through its clinics or the VA Retail Immunization Care Coordination Program at Walgreens for the 2019-2020 flu season.

“High dosage (HD) flu vaccines will not be offered this year by either VA medical facilities or Walgreens,” according to the VA website. “There is no cost to veterans enrolled in VA health care for quadrivalent vaccine at Walgreens. However, if you decide to get another vaccine or different type of flu vaccine, Walgreens may charge you, your private insurance, or Medicare.”

As trivalent vaccines, both the FluZone High Dose and another vaccine approved for individuals over age 65, FLUAD, are excluded from Walgreens’ immunization program. FLUAD contains an adjuvant that boosts immune response.

DoD did not contract for the high-dose vaccine either, although it may be available via direct vendor delivery to military treatment facilities, according to the Military Health System’s Seasonal Influenza Resource Center 2019-2020. FLUAD and Afluria quadrivalent are the two DoD-contracted vaccines this year.

Licensed influenza vaccines include eight shots and an intranasal spray. This year, the three trivalent formulations will protect against influenza A/Kansas/14/2017 (H3N2)-like virus, A/Brisbane/02/2018 (H1N1)pdm09-like virus, and B/Colorado/06/2017-like (Victoria lineage) virus. The quadrivalent formulations will also include a second influenza B lineage component, B/Phuket/3073/2013-like (Yamagata lineage) virus.

While the high-dose vaccine counters just three of the flu viruses most likely to be in circulation each year, “it generates four times the antigen level of a standard dose,” Russo explained. “As you age, the immune system becomes weaker. The theory is that building up antibodies and will create better immune response.”

The studies by Russo and her colleagues tested whether clinical results supported that theory. “We look at, in real life, are we preventing bad outcomes that can come with influenza.”

The effectiveness study focused on the same period of time as the cost-saving study, the five years from the 2010/2011 flu season through the 2014/2015 flu season. During that time, 158,636 veterans received the high-dose vaccine, and 3,480,288 received the standard dose.

The researchers determined that the high-dose vaccine reduced all-cause hospitalizations by 10% more than the standard dose. The higher dose provided an additional 18% benefit in terms of cardiorespiratory-associated hospitalizations and a 14% addition reduction in influenza and pneumonia-associated hospitalizations. The benefit was particularly notable, as veterans who received the high-dose vaccine tended to have more comorbidities prior to vaccination.

“The research shows that the high-dose vaccine reduces lab confirmed cases of influenza, hospitalizations associated with influenza, and death associated with influenza. That’s moving beyond what happens with the immune system to what happens in people’s lives when a vaccine is more effective,” Russo said.

The adjuvanted vaccine also may provide additional protection for older veterans. Some studies have found that FLUAD generates an immune response on par with that produced by an unadjuvanted trivalent vaccine, according to the CDC, but a Canadian study in patients over age 65 showed that it was significantly more effective in preventing laboratory-confirmed cases of the flu.

No head-to-head trials comparing FLUAD and FluZone High Dose have reported yet, although the VA is currently participating in a comparative study involving 500 long-term care facility residents. That study is scheduled to conclude in 2021.

Regardless of the specific vaccine used, the VA encourages all veterans to get a flu shot as early as possible to maximize protection throughout the flu season.

“Research shows that influenza vaccination is the most evidence-based practice for preventing what can be a serious and fatal condition,” said Russo. “Encouraging veterans to be vaccinated annually for influenza is a comprehensive strategy and a best practice. Mostly, though, it’s simply the right thing to do.”


  1. van Aalst R, Russo EM, Neupane N, Mahmud SM, Mor V, Wilschut J, Chit A, Postma M, Young-Xu Y. Economic assessment of a high-dose versus a standard-dose influenza vaccine in the US Veteran population: Estimating the impact on hospitalization cost for cardio-respiratory disease. 2019 Jul 26;37(32):4499-4503.
  2. Young-Xu Y, Snider JT, van Aalst R, Mahmud SM, Thommes EW, Lee JKH, Greenberg DP, Chit A. Analysis of relative effectiveness of high-dose versus standard-dose influenza vaccines using an instrumental variable method. Vaccine. 2019 Mar 7;37(11):1484-1490.

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