Cost-Effectiveness and Public Health Effect of Influenza Vaccine Strategies for U.S. Elderly Adults

Jonathan M. Raviotta, MPH; Kenneth J. Smith, MD, MS; Jay DePasse, BS; Shawn T. Brown, PhD; Eunha Shim, PhD; Mary Patricia Nowalk, PhD; Richard K. Zimmerman, MD, MPH


J Am Geriatr Soc. 2016;64(10):2126-2131. 

In This Article

Abstract and Introduction


Objectives: To compare the cost-effectiveness of four influenza vaccines available in the United States for persons aged 65 and older: trivalent inactivated influenza vaccine (IIV3), quadrivalent inactivated influenza vaccine (IIV4), a more-expensive high-dose IIV3, and a newly approved adjuvanted IIV3.

Design: Cost-effectiveness analysis using a Markov model and sensitivity analyses.

Setting: A hypothetical influenza vaccination season modeled according to possible U.S. influenza vaccination policies.

Participants: Hypothetical cohort of individuals aged 65 and older in the United States.

Measurements: Cost-effectiveness and public health benefits of available influenza vaccination strategies in U.S. elderly adults.

Results: IIV3 cost $3,690 per quality-adjusted life year (QALY) gained, IIV4 cost $20,939 more than IIV3 per QALY gained, and high-dose IIV3 cost $31,214 more per QALY than IIV4. The model projected 83,775 fewer influenza cases and 980 fewer deaths with high-dose IIV3 than with the next most-effective vaccine: IIV4. In a probabilistic sensitivity analysis, high-dose IIV3 was the favored strategy if willingness to pay is $25,000 or more per QALY gained. Adjuvanted IIV3 cost-effectiveness depends on its price and effectiveness (neither yet determined in the United States) but could be favored if its relative effectiveness is 15% greater than that of IIV3.

Conclusion: From economic and public health standpoints, high-dose IIV3 for adults aged 65 years and older is likely to be favored over the other vaccines, based on currently available data. The cost-effectiveness of adjuvanted IIV3 should be reviewed after its effectiveness has been compared with that of other vaccines and its U.S. price is established.


Influenza continues to be a major cause of morbidity and mortality in persons aged 65 and older in the United States. Every year, up to 250,000 hospitalizations due to influenza occur in this age group,[1] with up to 30,000 influenza-related deaths per year,[2] but protection afforded to older populations through influenza vaccination is unclear and controversial, leading to investigation of vaccination options for this group.[2] Four influenza vaccines are available in the United States for persons aged 65 and older: trivalent influenza vaccine (IIV3), which, until relatively recently, was the only option available; quadrivalent influenza vaccine (IIV4), which adds a second influenza B lineage to IIV3; a newer and more expensive high-dose IIV3; and a recent Food and Drug Administration (FDA)-approved adjuvanted IIV3, the U.S. price of which has not been determined and the effectiveness of which is unknown. A multicenter, randomized, controlled, Phase IIIb-IV study found better protection with high-dose IIV3 than IIV3 and a comparable safety outcome.[3] A trial-based cost-effectiveness analysis comparing these vaccines showed high-dose IIV3 to be less costly and more effective than IIV3;[4] other vaccines were not considered in this analysis.

Influenza vaccine choice in elderly adults poses some dilemmas. Head-to-head clinical trial effectiveness comparisons are limited to high-dose IIV3 vs IIV3, without comparisons with IIV4 nor adjuvanted IIV3. It is not clear whether the benefits of the newer vaccines are worth their added cost. In addition, there is currently only one U.S. high-dose IIV3 manufacturer, potentially limiting choice and bringing market forces into play in vaccine choice decisions. Finally, consideration of adjuvanted IIV3 requires ongoing observation to measure population comparative effectiveness and more specific pricing information.[5]

To investigate these dilemmas, a cost-effectiveness analysis was performed comparing, in the main analysis, IIV3, high-dose IIV3, and IIV4 in older individuals and exploring how model parameter variation might affect influenza vaccine decision-making in this vulnerable group. In a separate analysis, the favorability of adjuvanted IIV3 over the other vaccines was also explored in hypothetical scenarios.