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


Table 2 shows the base-case results. Per-person influenza vaccination and illness costs were $4.13 higher with IIV3 than with no vaccination and gained 0.00112 QALYs (~10 hours) at a value of $3,693 per QALY gained. IIV4 cost $2.02 more than IIV3 and gained 0.0001 QALYS, or $20,939 per QALY gained. High-dose IIV3, compared to IIV4, cost $31,214 per QALY gained.

From a public health standpoint, when model-based influenza outcome probabilities for the modeled cohort were applied to the 2013 U.S. population aged 65 and older (n = 44,704,074), IIV3 prevented 510,643 influenza cases, 21,498 hospitalizations, and 5,975 deaths; IIV4 prevented an additional 39,136 cases, 1,648 hospitalizations, and 458 deaths; and high-dose IIV3 prevented an additional 83,775 cases, 3,537 hospitalizations, and 980 deaths. When considering total population influenza vaccination and illness costs, IIV3 cost approximately $185 million more than no vaccination, IIV4 cost $90 million more than IIV3, and high-dose IIV3 cost $289 million more than IIV4.

One-way sensitivity analyses comparing IIV3, high-dose IIV3, and IIV4 showed that, under most circumstances, high-dose IIV3 most often cost less than $100,000 per QALY gained, but variation of four parameters (IIV3 effectiveness, relative effectiveness of high-dose IIV3 and IIV3, proportion of influenza caused by influenza B that was not an IIV3 component, influenza likelihood in unvaccinated individuals) caused high-dose IIV3 to cost more than $100,000 per QALY gained. Vaccination strategy favorability was most sensitive to variation of IIV3 effectiveness (base-case estimate 39%); if it was less than 10%, no vaccination was favored; if it was between 10% and 12.1%, IIV3 was favored; if it was between 12.1% and 15.5%, IIV4 was favored; and if it was greater than 15.5%, high-dose IIV3 was favored. Also, high-dose IIV3 cost more than $100,000 per QALY gained (and IIV4 was favored) if the relative increase in high-dose IIV3 effectiveness was less than 0.143 (base-case 0.242), the proportion of influenza due to uncovered influenza B was greater than 17.6% (base-case 7.7%), or influenza likelihood was less than 2.4% (base-case 5.9%). Individual variation of all other probability, cost, and utility parameters over their listed ranges in Table 1 and of the likelihood of receiving antiviral therapy did not affect the favorability of high-dose IIV3. Thus, results were sensitive to potential fluctuations in yearly influenza attack rates, virus variability, and vaccine effectiveness but not to other model parameters, including vaccination cost.

Recent studies have highlighted influenza vaccination effects on hospitalization,[3,12] with high-dose IIV3 resulting in lower influenza case rates and hospitalization rates than IIV3, with case and hospitalization rates moving similarly. These findings suggest that vaccination affects hospitalization rates through effects on influenza case rates and not by any vaccination-specific effects on hospitalization. Nevertheless, in sensitivity analyses, influenza hospitalization rates were specifically examined by varying case-hospitalization rates for all vaccines to explore possible differences in protection from hospitalization among vaccines. When case-hospitalization was decreased from 4.21% (base case) to 2.2%, the lowest value observed in a recent clinical trial,[3] high-dose IIV3 cost $32,766 per QALY gained (vs $31,214 per QALY gained in the base-case analysis) and $19,462 per QALY gained when case-hospitalization was 20%. When examining differential hospitalization protection among vaccines, if the IIV3 case-hospitalization rate was 5.7% or greater, then other strategies dominated IIV3 (more costly, less effective). Conversely, if high-dose IIV3 case-hospitalization was halved (to 2.1%), high-dose IIV3 was favored, costing $19,440 per QALY gained.

A cost-effectiveness acceptability curve (Figure 1.) depicts the probabilistic sensitivity analysis results showing, for each x-axis willingness-to-pay value, the probability that each strategy would be acceptable at that value over 5,000 model iterations. In this analysis, high-dose IIV3 was favored in 49.3% of iterations if willingness to pay was $50,000 per QALY gained and in 68.5% of iterations at $100,000 per QALY gained. If willingness to pay was $25,000 per QALY gained or more, high-dose IIV3 was the most likely strategy to be favored.

Figure 1.

Cost-effectiveness acceptability curve. Plot of the results of a probabilistic sensitivity analysis. Each increment on the x-axis of willingness to pay represents 5,000 complete model iterations for which the values for every variable are randomly selected from an appropriately parameterized distribution. The plotted values on the y-axis represent the percentage of iterations for which each strategy was cost-effective at the given willingness to pay. High-dose trivalent influenza vaccine strategy was favored if willingness to pay was $25,000 or greater per quality-adjusted life year gained.

In a secondary analysis, adding consideration of the newly licensed but unavailable adjuvanted IIV3,[20] scenarios varying its effectiveness and comparing it with the other vaccines and its cost were examined, given unresolved uncertainty in these areas.[5,20] These analyses assumed equal adverse event frequency between adjuvanted IIV3 and high-dose IIV3. Adjuvanted IIV3 was compared with the other strategies in a two-way sensitivity analysis, simultaneously varying adjuvanted IIV3 effectiveness relative to IIV3 (range 0 to 0.5 increased) and its price ($10–50). Over the entire price range and assuming willingness to pay of $100,000 per QALY gained, adjuvanted IIV3 was not favored if its relative effectiveness increase was less than 0.15 but was favored if its relative effectiveness was 0.32 or greater. If its relative effectiveness increase equaled that of high-dose IIV3 (0.242), it would be favored if its cost was less than the cost of high-dose IIV3 ($31.20).