Simulation runs were conducted of 1,000 trials of 1,000 pregnant women (or 1,000,000 total pregnant women traveling through the model) from both the societal and third-party payor perspectives for single and two-dose strategies. All simulations used the incremental cost-effectiveness ratio (ICER) of maternal influenza vaccination, calculated as follows:

shows how the optimal choice of whether to vaccinate a pregnant woman for influenza varies depending on prevalence of influenza, probability of death from influenza (severity), and the number of doses administered. When vaccination yields cost savings as well as better effectiveness, it “dominates” the no-vaccination option. In addition, when the ICER is ≤$50,000/QALY (a previously established threshold) an intervention is considered cost-effective.

| **Table 2**Incremental Cost - Effectiveness Ratios (ICERs) for Single - and 2 - Dose Maternal Influenza Vaccination using 73% and 63% Efficacy for Mothers and Neonates, Respectively (Societal Perspective) |

Simulations run from the societal perspective with a single-dose strategy were performed first. lists the respective ICERs using the base-case efficacy of 73% in pregnant women and 63% in neonates and compares single to two-dose strategies. These simulations demonstrate that when influenza prevalence is ≥30% and the probability of death from influenza is set equal to the expected seasonal influenza mortality, or the prevalence of influenza is ≥25%, and mortality is 2, 3 and 4 times the seasonal rate, vaccination is the dominant strategy. Single-dose maternal immunization was also found to be cost-effective when influenza prevalence was as low as ≥5% and the probability of death from influenza is set equal to the expected seasonal influenza mortality (or higher), or the prevalence of influenza is ≥2.5% and mortality is 2, 3 and 4 times the seasonal mortality rate. Simulations run from the third-party payor perspective (data not shown) likewise demonstrate that single-dose vaccination is the dominant strategy when influenza prevalence is ≥30% and the probability of death from influenza is set equal to the expected seasonal influenza mortality, or higher. Single-dose vaccination remains cost-effective when the prevalence of influenza is ≥2.5% and the probability of influenza-attributable mortality is greater than or equal to the expected seasonal rate.

Simulations using the two-dose strategy from societal perspective were subsequently performed using the same efficacy above (). A two-dose strategy also demonstrated cost-effectiveness when influenza prevalence is ≥7.5% and the probability of death from influenza is set equal to the expected seasonal influenza mortality and 2 times this rate, and when the prevalence of influenza is ≥5% and influenza-attributable mortality is 3 or 4 times the expected seasonal rate. Compared to the single-dose approach, cost-effectiveness at baseline vaccine efficacy is realized for the two-dose approach at a slightly higher prevalence of influenza (≥5% for 2-dose vs. ≥2.5% for 1-dose). This is noted for all levels of vaccine efficacy and mortality. A two-dose strategy, however, never dominates the no-vaccination approach.

Sensitivity analyses testing lower vaccine efficacies (25% and 50% for both maternal and neonatal efficacy) were performed from the societal perspective using both the single and two-dose strategies At the lowest presumed vaccine efficacy of 25%, vaccination remained cost-effective at influenza prevalence levels ≥ 7.5% for single-dose immunization at all levels of influenza-attributable mortality. Cost-effectiveness was realized for a two-dose immunization strategy when the prevalence of influenza is ≥ 12.5% (expected seasonal value) and the probability of mortality due to influenza is equal to expected seasonal influenza mortality, or when influenza prevalence is ≥ 10% and the probability of influenza-attributable mortality is 2, 3, or 4 times the expected seasonal mortality rate.

Increasing the vaccine efficacy to 50% demonstrates that a single-dose vaccination strategy is cost-effective when influenza prevalence is ≥ 5% and the probability of death from influenza is set equal to the expected seasonal influenza mortality, or higher. Cost-effectiveness is also realized for a two-dose approach when the prevalence of influenza is ≥ 10% and the influenza-attributable mortality rate is equal to the expected seasonal rate or twice that, or when prevalence of influenza is ≥ 7.5% and the probability of death from influenza is 3 or 4 times the expected seasonal mortality rate.

highlights the findings of a single-dose approach, comparing different vaccine efficacies and influenza prevalence, in addition to increasing levels of mortality (severity of infection). The two key factors noted to impact cost-effectiveness of both dosing strategies to the greatest extent are influenza prevalence and severity of illness.

shows the acceptability curves for different influenza prevalence levels when vaccine efficacy is 73% in the mother and 63% in the neonate and the probability of death from influenza is 1.05%. These curves demonstrate that when influenza prevalence is 12.5% and the maximum willingness-to-pay is $50,000, vaccinating pregnant women for influenza is cost-effective approximately 90% of the time. As the prevalence of influenza increases, the same probability of maternal vaccination yielding cost-effectiveness is achieved at lower willingness-to-pay thresholds (approximately $30,000 at 15% prevalence, $20,000 at 20%, and $15,000 at 25%).