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


A newer, more-expensive high-dose influenza vaccine is available for use in U.S. elderly adults. This analysis suggests that, even with its substantially higher per-dose cost ($21.51 more), high-dose IIV3 is an economically favorable strategy for U.S. adults aged 65 and older. Model projections of added public health benefit due to high-dose IIV3 use found substantially fewer influenza cases, hospitalizations, and deaths than with other vaccine options in U.S. elderly adults. Results were robust in sensitivity analyses but were sensitive to variation of vaccine effectiveness and influenza likelihood parameters. Most importantly, if the relative effectiveness of high-dose IIV3 over that of IIV4 is much lower than observed in clinical trials, high-dose IIV3 will no longer be the favored strategy. The newer adjuvanted IIV3 could be favored, but further consideration of this vaccine awaits comparative effectiveness data and pricing information.

The favorability of high-dose IIV3 over other vaccines in U.S. elderly adults largely hinges on the reproducibility of heightened high-dose IIV3 effectiveness, as seen in clinical trials, in population-based settings. Whether this is the case is unclear. An industry-sponsored trial provides evidence of greater high-dose vaccine effectiveness,[3,20] and similar results were found in an FDA-sponsored retrospective cohort study using U.S. Medicare claims data during the 2012/13 influenza season, with the high-dose influenza vaccine found to be 22% more effective in preventing influenza infections and hospitalizations than the standard-dose vaccine.[12] Future verification of heightened effectiveness will be required.

The CDC and its Advisory Committee on Immunization Practices (ACIP) have not expressed any preference regarding the influenza vaccines available for individuals aged 65 and older.[21] In making its recommendations, ACIP uses the Grading of Recommendations Assessment, Development and Evaluation approach to provide an evidence base for its deliberations,[22] in which evidence is graded based on type (e.g., randomized trials, observational studies) and strength.[22] It is likely that changes in CDC recommendations regarding high-dose IIV3 use in older adults will depend on further confirmation of industry-supported clinical trial findings. In any case, influenza morbidity and mortality in older Americans suggests the need for better protection than IIV3 affords. This analysis supports use of high-dose IIV3 to reduce influenza impact in elderly adults.

This analysis has some notable strengths and limitations. It was based on randomized controlled trial data that suggested significantly greater effectiveness with high-dose IIV3 use in elderly adults,[3] with those findings subsequently supported by a retrospective study.[12] A prior trial-based cost-effectiveness analysis compared IIV3 and high-dose IIV3 but did not include the other vaccines.[4] Extensive sensitivity analyses were performed in the current study, and the results were robust to simultaneous variation of all model parameters in a probabilistic sensitivity analysis but sensitive to individual variation of some vaccine effectiveness and influenza likelihood parameters, indicating areas where continued surveillance is needed. As in any modeling exercise, some simplifying assumptions were made, perhaps limiting model realism, but whenever possible, the assumptions consistently biased the model against vaccination strategies, for example, assuming that influenza vaccination affected only deaths due to influenza and not those due to other causes and that vaccinating elderly adults had no herd immunity effects. Thus, it is likely that the vaccination strategy cost-effectiveness values are somewhat more pessimistic than they would have been if assumptions without this consistent bias had been made, although the possibility of differential availability and affordability of higher-cost vaccines or how vaccine manufacturers might adjust prices based on availability and market share of newer vaccines, which are potential limitations to the analysis, was not considered. In addition, published sources, not Medicare claims data, were used for influenza-related healthcare use and costs, and thus the benefits of vaccination could have been underestimated; if this is the case, then vaccination would be even more favorable.

Development of a high-dose IIV4 is anticipated. When that occurs, the cost-effectiveness of this new vaccine will need to be compared with that of the existing vaccines. The development of new influenza vaccines will continue, highlighting the importance of continuing evaluation of what is gained using new vaccines and what those gains cost.