Fig 1.
Epidemiological and economic impact of influenza vaccine intervention.
The epidemiological and economic impact of influenza vaccine intervention includes the direct and indirect effects. The static model simulated only the direct effects, while the dynamic model simulates both the direct and indirect effects. Direct effect is due to the direct protection of the influenza vaccine among vaccinated individuals who generate protective immune response to influenza infection. Indirect effect is due to indirect protection among non-vaccinated individuals who are protected from influenza acquisition from effectively vaccinated individuals, (i.e.) in the absence of vaccination, influenza transmission will have occurred between these individuals.
Table 1.
Synthetic social network of Chicago.
Synthetic population of Chicago is generated and a social contact network is estimated through the following four steps.
Table 2.
The parameter values of the influenza pandemic simulations and their sources.
Fig 2.
Influenza incidence (average number of new cases per day) during the pandemic for no vaccine intervention and vaccine intervention scenarios.
The epidemic curves illustrate influenza incidence without and with vaccination intervention for the catastrophic, strong and moderate influenza pandemic scenarios. The number of cases is the average of new cases over 25 simulations. Higher attack rates cause the earlier, more severe, and shorter pandemic duration, compared to the less severe but longer pandemics. The vaccination intervention is applied 15 days after the start of pandemic and implemented for 60 days. The vaccine intervention scenarios are simulated at 40% efficacy and 40% compliance for all age and risk groups in the dynamic agent-based model.
Table 3.
Pandemic cost per capita, attack rate, and reproduction number for different severities of pandemic influenza in the base case scenario of no vaccine intervention.
Pandemic cost per capita is the average cost of influenza related health outcomes among infected individuals for death, hospitalization, outpatient visit, and ill but not seeking medical care. The attack rate is the proportion of population infected by influenza during the influenza pandemic. Reproduction number is the number of secondary cases caused by the index case in a susceptible population.
Table 4.
Pandemic cost per capita, attack rate, and reproduction number for catastrophic, strong and moderate pandemic influenza scenarios with and without vaccine intervention.
Pandemic cost per capita, attack rate and reproduction number with and without vaccine intervention is presented for catastrophic, strong and moderate influenza pandemic scenarios. The vaccine intervention is implemented at 40% compliance and 40% efficacy which decreases the pandemic cost per capita, attack rate and reproduction number. Pandemic cost per capita, attack rate and reproduction number are relatively lower in the dynamic model (direct + indirect effects) in comparison to the static model (direct effect only).
Table 5.
Cost of influenza related health outcomes for different age and risk groups.
The costs of influenza related health outcomes of death, hospitalization, outpatient, and ill but not seeking medical care are based on the study by Carias et al [39], and are updated to 2015 US dollars.
Fig 3.
Decision tree of health outcomes for influenza cases and related costs.
For each influenza case, the probability of the different health outcomes and related costs depend on the age and risk group of the patient. Patients with pre-existing medical condition have a high risk of experiencing severe influenza related health outcomes. The probability of each health outcome is assigned an uniform or triangular distribution [4]. For the uniform distribution, the lower and upper rate are presented; for triangular distribution, the lower, most probably, and higher rates are presented.
Table 6.
Computation of pandemic cost, pandemic cost per capita, net benefits and return on investment.
The formulations to compute pandemic cost, pandemic cost per capita, net benefits and return on investment are presented below for the scenarios of without and with vaccine intervention. Pandemic cost is the total cost associated with the health outcomes of influenza cases and the cost of vaccination, and pandemic cost per capita is the average pandemic cost per person. The net benefits is the difference in cost due to improved health outcomes from vaccination and the vaccination cost. Return on investment is the gain in net benefits relative to the vaccination cost.
Fig 4.
Pandemic cost per capita, attack rate and reproduction number in the catastrophic, strong and moderate influenza pandemic scenarios with and without vaccine intervention.
Pandemic cost per capita, attack rate and reproduction number are relatively lower in the dynamic model due to the combined impact of direct and indirect effects, in comparison to the static model which includes only the direct effect. Fig 4A: Pandemic cost per capita in the catastrophic, strong and moderate influenza pandemic scenarios with and without vaccine intervention. Fig 4B: Attack rate in the catastrophic, strong and moderate influenza pandemic scenarios with and without vaccine intervention. Fig 4C: Reproduction number in the catastrophic, strong and moderate influenza pandemic scenarios with and without vaccine intervention.
Fig 5.
Return on investment of vaccine intervention.
Return on investment is the gain in net benefits relative to the vaccination cost, that is, dollars saved per $1 investment in vaccine intervention. Economic impact of the vaccine intervention includes both the direct and indirect effects. The direct effect is evaluated from the static model, and the direct and indirect effects is evaluated from the dynamic model.
Table 7.
Pandemic cost, net benefits and return on investment.
Pandemic cost is the total cost associated with the health outcomes of influenza cases and the cost of vaccination. Net benefits are the difference in cost due to improved health outcomes from vaccination and the vaccination cost. Return on investment is the gain in net benefits relative to the vaccination cost, that is, dollars saved per $1 investment in vaccine intervention.
Table 8.
Risk of death, total deaths, net benefits and return on investment for different age and risk groups in the catastrophic, strong, and moderate influenza pandemic scenarios.
Risk of death is estimated based on the number of influenza related deaths per 100,000 subpopulation for the specific age and risk groups. Total deaths is estimated based on the proportion of influenza related deaths for the specific age and risk groups among total influenza related deaths. Net benefits are the difference in cost due to improved health outcomes from vaccination and the vaccination cost. Return on investment is the gain in net benefits relative to the vaccination cost, that is, dollars saved per $1 investment in vaccine intervention.
Table 9.
Prioritization of influenza vaccine intervention.
Prioritization of influenza vaccine intervention among different age and risk groups based on different criteria: risk of death, total deaths, net benefits, and return on investment. aRisk of death is estimated based on the number of influenza related deaths per 100,000 subpopulation for the specific age and risk groups. Risk of death is the highest among the high risk 65+ years subpopulation in the catastrophic influenza and it is the highest among high risk 0–19 years subpopulation in the strong, and moderate influenza pandemic scenarios. bTotal deaths is estimated based on the proportion of influenza related deaths for the specific age and risk groups among total influenza related deaths. The proportion of influenza related deaths is the highest among the high risk 20–64 years subpopulation in the catastrophic, strong, and moderate influenza pandemic scenarios. cNet benefits are the difference in cost due to improved health outcomes from vaccination and the vaccination cost. Net benefits are the highest among the high risk 20–64 years subpopulation in the catastrophic, strong, and moderate influenza pandemic scenarios. dReturn on investment is the gain in net benefits relative to the vaccination cost, that is, dollars saved per $1 investment in vaccine intervention. Return on investment is highest among the high risk 0–19 years subpopulation in the catastrophic, strong and moderate influenza pandemic scenarios.
Fig 6.
Prioritization of influenza vaccine intervention.
Prioritization of influenza vaccine intervention among different age and risk groups based on different criteria: risk of death, total deaths, net benefits, and return on investment. Fig 6A: Risk of death is estimated based on the number of influenza related deaths per 100,000 subpopulation for the specific age and risk groups. Risk of death is the highest among the high risk 65+ years subpopulation in the catastrophic influenza and it is the highest among high risk 0–19 years old among strong, and moderate influenza pandemic scenarios. Fig 6B: Total deaths is estimated based on the proportion of influenza related deaths for the specific age and risk groups among total influenza related deaths. The proportion of influenza related deaths is the highest among the high risk 20–64 years subpopulation in the catastrophic, strong, and moderate influenza pandemic scenarios. Fig 6C: Net benefits are the difference in cost due to improved health outcomes from vaccination and the vaccination cost. Net benefits are the highest among the high risk 20–64 years subpopulation in the catastrophic, strong, and moderate influenza pandemic scenarios. Fig 6D: Return on investment is the gain in net benefits relative to the vaccination cost, that is, dollars saved per $1 investment in vaccine intervention. Return on investment is highest among the high risk 0–19 years subpopulation in the catastrophic, strong and moderate influenza pandemic scenarios.
Fig 7.
Sensitivity analysis of vaccine compliance, vaccine efficacy and vaccine start date, and impact on attack rate.
Univariate sensitivity analysis for vaccine compliance rates of 10%, 40%, 60% and 80% (Fig 7A), vaccine efficacy rates of 10%, 20%, 30%, 40%, 50% and 60% (Fig 7B) and vaccine start dates after epidemic onset of day 15, day 30, day 60 and day 90 (Fig 7C), and their impact on attack rates for catastrophic, strong, and moderate influenza pandemic scenarios with no vaccine intervention (base case) and vaccine intervention (static and dynamic models).
Fig 8.
Sensitivity analysis of vaccine compliance and impact on return on investment.
Univariate sensitivity analysis for vaccine compliance rates of 10%, 40%, 60% and 80%, and their impact on return on investment for catastrophic (Fig 8A), strong (Fig 8B) and moderate (Fig 8C) influenza pandemic scenario in the static (direct benefit) and dynamic (direct + indirect benefits) models.
Fig 9.
Sensitivity analysis of vaccine efficacy and impact on return on investment.
Univariate sensitivity analysis for vaccine efficacy rates of 10%, 20%, 30%, 40%, 50% and 60%, and their impact on return on investment for catastrophic (Fig 9A), strong (Fig 9B) and moderate (Fig 9C) influenza pandemic scenario in the static (direct benefit) and dynamic (direct + indirect benefits) models.
Fig 10.
Sensitivity analysis of vaccine start date and impact on return on investment.
Univariate sensitivity analysis for vaccine start dates after epidemic onset of day 15, day 30, day 60 and day 90, and their impact on return on investment for catastrophic (Fig 10A), strong (Fig 10B) and moderate (Fig 10C) influenza pandemic scenario in the static (direct benefit) and dynamic (direct + indirect benefits) models.