Cost-effectiveness of annual trivalent inactivated influenza vaccine program by age and risk status

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Methods A state transition simulation model was constructed to estimate the health and economic outcomes of IIV3 vaccination compared to no vaccination for hypothetical cohorts of Zhejiang province stratified by age and risk status. Model input parameters were derived from multiple sources. The analysis used societal perspectives and a one-year time horizon, and permanent outcomes were also included. The primary outcome was the incremental cost-effectiveness ratio (ICER), with expression of US dollars per quality adjusted life years (QALYs) gained. Results In non-high risk subgroups, the ICER ranged from $ 6268/QALY(adults aged 50–64 years) to $ 11260/QALY (children aged from 6 months to 4 years). In high risk subgroups, the ICER ranged from cost-saving (adults aged ≥ 65 years) to $ 5260/QALY (children aged from 6 months to 4 years). Results were most sensitive to changes in the probability of influenza illness, vaccine effectiveness, probability of systematic reactions for adults aged 18–49 years with non-high risk status, while were most sensitive to changes in probability of influenza illness, cost of hospitalization, probability of death for the same subgroup. Conclusions Our findings indicated the ICERs of annual influenza vaccination varied by age and risk status but was less than one time of the Gross Domestic Product (GDP) per capita of Zhejiang province ( $ 17745 in 2023), which remained cost-effective for all-age and different risk status groups from a societal perspective. Influenza Vaccination Cost-effectiveness Trivalent inactivated influenza vaccine Risk Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Influenza circulates annually and causes substantial morbidity and mortality, with the highest burden in adults aged ≥ 65 years and children aged < 5 years. Influenza caused 3–5 million severe cases and 290,000-650,000 deaths throughout the world annually[ 1 – 2 ]. Most of the influenza related deaths or hospitalizations occurred in elders aged ≥ 65 years and children aged < 5 years[ 3 ]. A meta analysis from mainland China found the influenza-related outpatient visit rate ranged from 0.1 to 7.4 per 1000 persons[ 4 ]. The influenza-related hospitalization rates were also higher among children and adolescents, with 384 per 100,000 children aged < 5 years and 112 per 100,000 children aged < 15 years[ 5 ]. The influenza-related all-age mortality was 23 per 100,000 persons and the mortality among adults aged ≥ 65 years was significantly higher than that for those aged < 65 years[ 2 ]. Vaccine is one of most effective inters to prevent influenza. Almost one-third of the World Health Organization (WHO) Member States recommended influenza vaccination for the entire population or persons with high risk[ 6 ]. Influenza vaccination had been incorporated into the national immunization program (NIP) of many developed countries and some upper middle-income countries. Vaccination programs in mainland China are categorized into NIP and non-NIP. The former are free of charge but mandatory, while the latter, including influenza vaccine, are self-funded and optional. Since the current self-paid policy, the coverage of influenza vaccination for all-age population is extremely low remaining around 2%[ 7 – 8 ]. Chinese vaccine administration law, which was issued in 2019, recommended the gradual incorporation of self-funded vaccines into NIP. In the transitional period, local health authorities were encouraged to introduce new vaccines into the local immunization program and release the free-administration policy before NIP policy at national level. Currently, Zhejiang province provide the trivalent inactivated influenza vaccine (IIV3) to adults aged > 70 years and it could significantly improve the vaccination coverage from 2–37%. A government-funded influenza vaccination policy could not only reduce the disease burden by improving vaccination coverage, but also would improve public trust in vaccines[ 9 ]. Since the 2009 pandemic influenza A(H1N1) virus circulated as one of the seasonal influenza viruses, the epidemiologic characteristic of seasonal influenza had been changed[ 1 , 11 ]. Prior to 2009, influenza A/H3 predominant seasons were associated with more severe influenza-related health outcomes, but a recent epidemiologic study on influenza observed higher incidence of influenza illness in working-age adults[ 12 ]. Moreover, the surveillance data suggested that younger working-age adults now experience more severe influenza related illness during influenza A/H1 predominant seasons rather than influenza A/H3 predominant seasons[ 13 ]. Since the 2009 pandemic influenza A influenza(H1N1) strain is now circulating as part of the set of seasonal influenza viruses, the pattern of vaccine-averted influenza events across age and risk strata may differ. Since 2010, the Advisory Committee on Immunization Practices (ACIP) implemented a universal influenza vaccination recommendation for all persons aged ≥ 6 months and encouraged the use of more convenient settings to improve the coverage and reduce the cost[ 14 ]. Given the changes in recommendations from the latest Chinese vaccine administration law and the changes in the epidemiology of influenza, many public health authorities and experts are calling for the influenza vaccine included into NIP, providing free vaccination for all-age group aged ≥ 6 months. Importantly, a cost-effectiveness evaluation is needed to inform decision-makers of whether to publicly fund influenza vaccination at local level. Policy decisions at various levels are driven by the uncertainties on disease burden, the unclear picture of demographic structure and socioeconomic level. Hence, the objective of this study was to evaluate the health and economic outcomes related to annual IIV3 program for population aged ≥ 6 months by age and risk status based on the new evidence and under the context of Zhejiang province. 2. Methods 2.1 Study design The state-transition simulation model was applied to assessing the health and economic outcomes for annul influenza vaccination. The hypothetical cohorts used in this study were constructed based on the 7th census data in 2020, which could reflect the differences in the influenza epidemiologic characteristics and vaccine effectiveness and would accurately estimate the cost-effectiveness of vaccination among different cohorts. Specifically, the general population were stratified by age as follow: 6 months-4 years, 5–17 years, 18–49 years, 50–64 years and ≥ 65 years. Each cohort (age group) was further stratified by risk status as defined by China center for disease control and prevention (CDC): those at higher risk for influenza-related complications (‘high risk’) or not (‘non-high-risk’)[ 15 ]. Besides, cohort aged ≥ 65 years were all assumed as high risk for influenza-related complications. Finally, there were 9 separate subgroups for the data analysis. The time horizon was set to one year as most influenza cases and complications occurred within a single influenza season (6 months). Permanent outcomes, such as death and sequela following influenza-related hospitalization, were included for the duration of a lifetime. This study was performed from a societal perspective and all model input parameters were derived from published sources, supplemented by expert input where data were scarce. The model was programmed using TreeAge Pro 2019 software. 2.2 Model construction Figure 1 represented the simulation model, including influenza- and vaccination- related health states. During a given year, a person could experience uncomplicated influenza, influenza-related outpatient visit, influenza-related hospitalization, influenza-related death or no influenza-related health event. For those with an influenza-related hospitalization, some would also experience sequelae associated with influenza. For person been vaccinated, vaccination-related adverse reaction, like injection site reaction and systematic reaction were also included. 2.3 Vaccination strategy The vaccination strategy in the model was providing a free IIV3 for all-age group aged ≥ 6 months. The vaccination program strategy was defined as vaccination with any available influenza vaccine on the market, although there might be more than ten influenza vaccine manufactures in mainland China. Other types of influenza vaccine, such as quadrivalent inactivated influenza vaccine and trivalent live attenuated influenza vaccine, were not considered into our analysis for two reasons. First, there had been no confirmed detections of circulating B/Yamagata lineage viruses since March 2020 globally. Second, the trivalent live attenuated influenza vaccine was only applied for use among individual aged 3–17 years, not the all-age population. 2.4 Parameters Influenza-related outcomes included episodes of influenza illness (outpatient visit or not), influenza-related hospitalization (with and without sequelae), and influenza-related death. We assumed that the incidence of influenza illness would not vary with risk status while the probability of complications following influenza would vary by risk status. This hypothesis was made due to insufficient evidence and we want to make a conservative approach to the results. Incidence of influenza illness, outpatient visits, hospitalizations, and death by both age were derived using published data from 2017-18 influenza seasons[ 16 ]. The incidence of outpatient visits by risk status were estimated based on the proportion of high-risk and non-high risk persons reporting care-seeking studies[ 17 ]. The incidence of hospitalization and death by risk status were derived from a study through using the proportion of influenza confirmed hospitalizations with at least one high-risk condition[ 18 ]. The probability of influenza-related sequelae was based on studies on influenza-related neurological complications[ 19 ]. As the available IIV3 were made by many manufactures in China, we assumed to use an average vaccine effectiveness estimate to reflect all influenza vaccine types and for different age groups, which was derived from the US Flu Vaccine Effectiveness Network[ 20 ]. Vaccination-related adverse events were also assumed to be similar across all vaccine types from different manufactures, including episodes of injection site reactions and systematic reactions. A very small proportion of vaccinee was assumed to die or experience sequelae after vaccination. The incidence of adverse reactions was extracted from published reports[ 21 – 24 ] (Table 1 ). Table 1 Probability parameters in the model Variable Level Base Case Range Distribution Source Probability of influenza 6m-4y 0.13 0.04–0.26 Beta 16 5-17y 0.10 0.03–0.19 18-49y 0.07 0.02–0.14 50-64y 0.13 0.02–0.31 ≥ 65y 0.08 0.01–0.21 Probability of outpatient visit following influenza 6m-4y NHR 0.66 0.64–0.69 Beta 16,17 5-17y NHR 0.51 0.49–0.53 18-49y NHR 0.36 0.34–0.37 50-64y NHR 0.40 0.38–0.42 6m-4y HR 0.78 0.75–0.80 5-17y HR 0.60 0.57–0.62 18-49y HR 0.45 0.43–0.48 50-64y HR 0.49 0.47–0.52 ≥ 65y HR 0.56 0.54–0.58 Incidence of hospitalization following influenza (/10000 population) 6m-4y NHR 5.21 1.49–11.18 Beta 16,18 5-17y NHR 1.51 0.22–1.68 18-49y NHR 1.27 0.19–1.39 50-64y NHR 10.18 4.28–12.08 6m-4y HR 62.74 18.04-134.56 5-17y HR 16.54 4.75–35.51 18-49y HR 22.81 6.55–48.94 50-64y HR 41.85 7.25-104.62 ≥ 65y HR 75.53 10.27-205.18 Incidence of death following influenza (/10000 population) 6m-4y NHR 0.05 0.00-0.25 Beta 16,18 5-17y NHR 0.02 0.00-0.14 18-49y NHR 0.03 0.00-0.12 50-64y NHR 0.10 0.01–0.29 6m-4y HR 0.64 0.00-2.99 5-17y HR 0.37 0.00-2.91 18-49y HR 1.00 0.09–4.91 50-64y HR 2.49 0.34–7.51 ≥ 65y HR 8.32 1.09–23.47 Probability of sequela following influenza-related hospitalization - 0.01 0.00-0.02 Beta 19 Vaccine effectiveness 6m-4y 0.46 0.37–0.53 20 5-17y 0.43 0.28–0.54 18-49y 0.35 0.24–0.45 50-64y 0.40 0.24–0.53 ≥ 65y 0.27 0.15–0.36 Probability of injection site reaction following influenza vaccination 6m-4y 0.008 0.002–0.017 Beta 21–24 5-17y 0.001 0.000-0.002 > 18y 0.011 0.000-0.044 Probability of systematic reaction following influenza vaccination 6m-4y 0.013 0.001–0.025 Beta 21–24 5-17y 0.004 0.000-0.008 > 18y 0.011 0.000-0.044 Probability of death following influenza vaccination(/10000 doses) - 0.01 Base ± 20% Beta 21–24 Probability of sequelae following influenza vaccination(/10000 doses) - 0.0001 Base ± 20% Beta 21–24 Discount rate - 0.03 0.02–0.05 Uniform - NHR: non-high risk; HR: high risk Cost estimates included direct medical, direct non-medical, and opportunity costs. The cost of self-medication for influenza was derived from a survey in Jiangsu Province, China [ 25 ]. The cost of outpatient and hospitalizations were based on a national survey[ 26 ]. The cost of sequelae following influenza vaccination or influenza hospitalization was obtained from a previous study[ 27 ]. Vaccination costs included direct vaccine dose cost, administration service costs, syringe cost, which were derived from a national survey[ 28 ]. Children aged 6–35 months were given 2 doses of influenza vaccine as recommended China CDC. The cost due to adverse reactions following IIV3 vaccination was obtained from published literature[ 29 ]. The productivity loss was calculated by multiplying the time loss due to influenza illness by the average daily productivity in 2023 in Zhejiang province, only for individual aged 18–59 years. Where appropriate, unit costs were converted into 2024 US dollars ( $ 1 = CNY7.10). All costs and utility were adjusted to 2024 values by using the discount rate of 3% (Table 2 ). Table 2 Cost parameters in the model Variable Base Case Range Distribution Source OTC medications for minor influenza $ 5.81 $ 4.01–6.69 Lognormal 25 Outpatient visit for influenza $ 137.04 Base ± 20% Lognormal 26 Hospitalization for influenza $ 1384.79 Base ± 20% Lognormal 26 Sequelae following influenza-related hospitalization $ 749958 $ 0-1543176 Lognormal 27 Influenza vaccine price/dose $ 2.82 Base ± 20% Lognormal 28 Syringe price/dose $ 0.17 Base ± 20% Lognormal 28 Service cost/dose $ 3.72 Base ± 20% Lognormal 28 Physician visit for injection site reaction following influenza vaccination $ 290 Base ± 20% Lognormal 29 Physician visit for systematic reaction following influenza vaccination $ 293 Base ± 20% Lognormal 29 Cost for sequelae following influenza vaccination $ 749958 Base ± 20% Lognormal 27 Productivity losses for non-medically attended influenza* 0.5d - - 30 Productivity losses for medically attended influenza* 2.5d - - 30 Productivity losses for influenza-related hospitalization* 3.8d - - 30 Productivity losses for systematic reaction following influenza vaccination* 0.5d - - 30 Daily productivity* $ 52.25 - - Local data *: Productivity losses parameters only for individuals aged 18-59y NHR: non-high risk; HR: high risk The health utility was assessed by the quality-adjusted life years (QALYs), which were the main measure of health benefits. Health states in the model were primarily temporary except for sequelae or death. Each temporary health state would cause a loss in QALYs that was subtracted from the total QALYs, which were estimated through the discounted life expectancy for every subgroup. The utility weight associated with each health state and the duration of influenza illness were derived from an EQ-5D survey and a trade-off survey of US adults [ 30 – 31 ]. QALYs loss for each health state were calculated by multiplying the utility weight for the health state by the duration of the health state. For example, QALYs loss for permanent sequelae were calculated by multiplying the relevant utility weight by the remaining life expectancy (Table 3 ). Table 3 Quality parameters in the model Variable Level Base Case Range Age Weights Duration Distribution Source Utility decrement for influenza illness 6m-4y - - 4.7x 7d Normal 30,31 5-17y - - 3.0x 18-49y 0.008 0.008–0.009 50-64y - - 0.9x ≥ 65y - - 2.6x Utility decrement for hospitalization 6m-4y - - 2.2x 11.8d Normal 30,31 5-17y - - 1.7x 18-49y 0.017 0.015–0.018 50-64y - - 1.0x ≥ 65y - - 1.5x Utility decrement for systematic reaction following influenza vaccination - 0.0012 0.001–0.002 - 3d Normal 30 Utility for sequelae - 0.0198 0.018–0.022 - - - 30,31 Utility for death - 0 - - - - 30 Life expectancy 6m-4y 77.52y - - - - Local data 5-17y 68.67y - - - - 18-49y 49.37y - - - - 50-64y 27.12y - - - - ≥ 65y 13.51y - - - - 2.5 Data analysis The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated by dividing the discounted net costs by discounted net QALYs. Secondary outcomes included the number of influenza cases averted, hospitalizations averted, deaths averted, adverse reactions occurred, QALYs gained, and net costs. The base-case analysis compared the vaccination program strategy to no vaccination using the societal perspective. One-way sensitivity analyses were conducted for most parameters among cohort aged 18–49 years by different risk status, in which each parameter value was varied over a plausible range to determine the impact from each parameter on the ICER. The plausible ranges were estimated by using confidence intervals (CI) from relevant studies or ± 20% of base values if the confidence interval was not available. Probabilistic sensitivity analysis (PSA) was also implemented to assess the effects of parameter uncertainty by defining parameters using a distribution of possible values and running the model for 10,000 iterations to derive 95% CI. 3. Results 3.1 Base-case analysis The results of base-case analysis were summarized in Table 4 . The number of influenza cases averted compared to no vaccination varied by age but was highest for children aged from 6 months to 4 years, with 60 influenza cases averted per 1000 vaccinated. The avert case number did not varied by risk status as we assumed the probability of influenza illness was the same among different risk status. On the other hand, the number averted hospitalization and death varied with age group and risk status. Hospitalizations averted were highest among children aged from 6 months to 4 years (2.89 hospitalizations averted per 1000 vaccinated), followed by older persons aged ≥ 65 yeas (2.04 hospitalizations averted per 1000 vaccinated). The number of averted deaths were highest for older persons aged ≥ 65 years, with 0.22 deaths averted per 1000 vaccinated. Table 4 Projected net costs health benefits and risks of influenza vaccination by age and risk status (per 1000 vaccinated) Risk group Age group Net cost QALYs gained Cases averted Hospitalizations averted Deaths averted Adverse events incurred Non-high risk 6m-4y $ 11260 2.5 60 0.29 0.002 21 5-17y $ 10205 2 42 0.07 0.002 8 18-49y $ 9705 2 25 0.05 0.001 11 50-64y $ 6268 0.5 52 0.41 0.006 11 High risk 6m-4y $ 5260 4.1 60 2.89 0.03 21 5-17y $ 5103 3.8 42 0.71 0.02 8 18-49y $ 4385 3.6 25 0.8 0.04 11 50-64y $ 2207 2.9 52 1.68 0.1 11 ≥ 65y - $ 904 3.9 21 2.04 0.22 11 The incidence of adverse reactions related to influenza vaccine was highest among children aged from 6 months to 4 years, with 21 adverse reactions occurred per 1000 vaccinated. The incidence also did not vary between different risk status as we assumed its probability was same. Based on 1000 persons being vaccinated, annual influenza vaccination strategy was to be cost-saving for older persons aged ≥ 65 years with high-risk status. The net cost of annual influenza vaccination for other subgroups ranged from $ 2207 per 1000 vaccinated for adults aged 50–64 years to $ 11260 per 1000 vaccinated for children aged from 6 months to 4 years. Annual influenza vaccination could yield net positive QALYs for all subgroups, indicating health benefits of vaccination exceeded the risk of adverse reactions related to vaccine. The net QALYs gained were highest for children aged from 6 months to 4 years with high risk status (4.1 QALYs per 1000 vaccinated), followed by older persons aged ≥ 65 years with high-risk status (3.9 QALYs per 1000 vaccinated). Table 5 indicated the ICER of annual influenza vaccination varied by age and risk status. In non-high risk subgroups, the ICER ranged from $ 6268/QALY (adults aged 50–64 years) to $ 11260/QALY (children aged from 6 months to 4 years), and was most favorable for adults aged 50–64 years ( $ 6268/QALY). In high risk subgroups, influenza vaccination was cost-saving for adults aged ≥ 65 years. For the remaining high-risk subgroups, influenza vaccination yielded ICERs that ranged from $ 2207/QALY (adults aged 50–64 years) to $ 5260/QALY (children aged from 6 months to 4 years). Table 5 Incremental cost-effectiveness ratios by age and risk status Risk group Age group $ /QALY gained $ /Cases averted $ /Hospitalizations averted $ /Deaths averted Non-high risk 6m-4y $ 11260 $ 4504 $ 187.67 $ 38828 5-17y $ 10205 $ 5103 $ 242.98 $ 145786 18-49y $ 9705 $ 4853 $ 388.20 $ 194100 50-64y $ 6268 $ 12536 $ 120.54 $ 15288 High risk 6m-4y $ 5260 $ 1283 $ 87.67 $ 1820 5-17y $ 5103 $ 1343 $ 121.50 $ 7187 18-49y $ 4385 $ 1218 $ 175.40 $ 5481 50-64y $ 2207 $ 761 $ 42.44 $ 1314 ≥ 65y - $ 904 - $ 232 - $ 43.05 - $ 443 3.2. Sensitivity analyses In one-way sensitivity analyses, the ICERs for influenza vaccination were most sensitive to changes in probability of influenza illness, vaccine effectiveness, probability of systematic reactions for adults aged 18–49 years with non-high risk status, while were most sensitive to changes in probability of influenza illness, cost of hospitalization, probability of death for adults aged 18–49 years with high risk status (Fig. 2–3). Cost-effectiveness acceptability curves were depicted using probabilistic sensitivity analyses (Fig. 4). Cost-effectiveness acceptability curves characterize uncertainty in economic evaluations and represent the probability that an intervention is cost-effective under a range of cost-effectiveness thresholds. Under the threshold of $ 5000/QALY, the probability that annual influenza vaccination strategy would range from 7.51% (children aged from 6 months to 4 years) to 81.12% (adults aged 50–64 years) for non-high risk subgroups, and ranged from 34.32% (children aged from 6 months to 4 years) to 99.87% (older person aged ≥ 65 years) for high risk subgroups. 4. Discussion Seasonal influenza imposes a significant health and economic burden in China, particularly in elders with high risk for severe consequences of infection. We evaluated the cost-effectiveness of annual IIV3 universal vaccination strategy among population aged ≥ 6 months, under the Zhejiang province-specific demographic data. The highest benefit of annual IIV vaccination program was observed in elders aged ≥ 65 years with high risk, and this strategy could also induce the net health gains for all other subgroups, with net cost incurred simultaneously. In terms of health gains from IIV3, our findings were consistent with results from previous reports[ 32 – 37 ], which demonstrated IIV3 could reducing the number of influenza cases, hospitalizations, and deaths, and being cost saving. Our analysis indicated that the ICER was cost-saving among elders aged ≥ 65 years with high risk. We assumed that it would be associated with the high incidence of death or complication due to influenza infection among this vulnerable subgroup and more death or severe cases would be averted from IIV3 vaccination. Influenza vaccination strategy required a net investment to produce health benefits for most subgroups in this study. Previous reports had indicated that, comparing with no intervention, IIV3 was cost-effective when used in healthy children, healthy adults aged 50–64 years and the elderly[ 38 – 40 ]. In our study, the ICER ranged from $ 6268/QALY to $ 11260/QALY for age groups with non-high risk, and ranged from cost-saving to $ 5260/QALY for age groups with high risk. In 2023, the Gross Domestic Product (GDP) per capita of Zhejiang province was $ 17745, which was higher than the ICERs for all age group with or not with high risk. It demonstrated the annual IIV3 vaccination strategy was still cost-effective if we used one time of the GDP per capita. The vaccine effectiveness for elders aged ≥ 65 years used in our model was lower than previously assumed[ 41 ], which might influence the economic value of influenza vaccination strategy. In the base-case analysis, we found influenza vaccination for elders aged ≥ 65 years was cost-saving, assuming the vaccine effectiveness was at 27%. Given the substantial burden of influenza illness in elders, our results provided important information demonstrating influenza vaccination for the older age group even if vaccine effectiveness was lower than previously assumed. Studies on the cost-effectiveness of influenza vaccination program among healthy working-age (18–49 years) adults in the China were very limited. Among the small number of health economic studies from other countries, influenza vaccination was generally favorable for this age group[ 42 – 43 ]. However, these reports assumed that the vaccination scenario was in low-cost settings and the outcomes varied. These reports also found that parameters including incidence of influenza, cost of vaccination, vaccination effectiveness, productivity loss and daily productivity would significantly influence the cost-effectiveness results, which were similar with the findings in our analysis. The cost-effectiveness thresholds of $ 5000/ QALY for this subgroup were applied in our sensitive analysis, which were lower than the commonly used effectiveness thresholds used in previous studies. For example, the threshold range of GB€20000 to 30000 was considered as cost-effective in a report from Great Britain[ 44 ]. Canadian Agency for Drugs and Technologies in Health used a threshold of CAD $ 50000–100000 in the pharmaceutical health economics evaluation[ 45 ]. Also, a threshold of US $ 50000 was commonly used in similar studies in US[ 46 ]. There were several reasons for the difference in the threshold settings. First, it might be due to the lower probability of influenza case and influenza-related complication, underscoring the potential economic value of influenza vaccination in different countries, especially for high-risk individuals. For example, a cost-effectiveness study of influenza vaccination among pregnant women found the influenza vaccination resulted in an ICER of $ 260000/QALY during a very low incidence season[ 47 ]. Second, it would be related to the difference in social and economic development between Zhejiang province and these developed countries. The second panel on cost-effectiveness in health and medicine recommended that productivity cost should be included in the numerator of the formula of calculating ICER as a monetary term[ 48 ]. However, other reports would not include the productivity loss into cost since it would be captured in the QALY loss with influenza health states, and causing double counting if including it as an additional cost[ 49 – 50 ]. However, we assumed that the loss in QALYs associated with influenza only considered the life and adjusted life losses due to the disease itself when these data came from field investigation, which might not include the indirect cost. Moreover, the annual influenza vaccination program would be more attractive from the social perspective if the productivity losses included in the analysis. There were several limitations to this study. First, indirect effects of reduced transmission were not included in this study because assumptions about the effectiveness of vaccines to reduce transmission were still uncertain for seasonal influenza. If these indirect effects were included, the results would be more favorable for vaccination. Second, our model did not include family spillover effects of illness, such as the burden of informal caregiving. If these effects were included, the cost-effectiveness of vaccination would also be more favorable. Third, the difference in the probability of experiencing symptomatic influenza among individuals with or without high risk was not considered in this analysis, and if a high risk individual was at greater risk of experiencing symptomatic compared to a non-high risk individual, then vaccination would be more favorable for high risk subgroups. Lastly, the analysis did not include the differences in duration of symptoms and complications from influenza between vaccinated versus unvaccinated individual. If vaccinated individual experienced a shorter duration of illness compared to unvaccinated individual, then vaccination would be more economically attractive. 5. Conclusions This study provided the crucial information for policy-makers assessing the universal influenza vaccination recommendation. Our findings indicated that influenza vaccination produces cost-effectiveness ratios that were less than commonly used cost-effectiveness thresholds for all subgroups. After incorporating updated epidemiologic and vaccine effectiveness data, annual influenza vaccination remained cost-effective for all-age and different risk status groups from a societal perspective. Declarations Ethics approval and consent to participate: This study was exempted for ethics approval as it did not contain any personal information and include no human research participants. Clinical Trial: Not applicable. Consent for publication: Not applicable. Availability of data and material: Data was provided within the manuscript. Competing interests: The authors declare that they have no competing interests. Funding: This study was funded by medical and health science and technology project of Zhejiang province (Grant number: 2023KY633). Author Contributions: YH and ZY developed the specific study protocol, constructed the model for cost effectiveness analysis. CJ collaborated in the study protocol and in the construction and refinement of the model. JZ and YX contributed to the collection of data required for the input parameters. YH and ZY initiated the study design, supervised the project, and directed the analysis and manuscript writing. All authors had carefully revised the draft of the manuscript. Acknowledgments: We would like to thank the following representatives of various organizations who formed our local expert panel and participated in our consultative meetings and interviews and contributed technical support and expert opinions. References Budd AP, Beacham L, Smith CB, Garten RJ, Reed C, Kniss K, Mustaquim D, Ahmad FB, Cummings CN, Garg S, Levine MZ, Fry AM, Brammer L. Birth Cohort Effects in Influenza Surveillance Data: Evidence That First Influenza Infection Affects Later Influenza-Associated Illness. J Infect Dis. 2019 Jul 31;220(5):820-829. doi: 10.1093/infdis/jiz201. PMID: 31053844; PMCID: PMC6669091. 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The economic burden of influenza-associated outpatient visits and hospitalizations in China: a retrospective survey. Infect Dis Poverty. 2015 Oct 6;4:44. doi: 10.1186/s40249-015-0077-6. PMID: 26445412; PMCID: PMC4595124. Zhang H, Garcia C, Yu W, Knoll MD, Lai X, Xu T, Jing R, Qin Y, Yin Z, Wahl B, Fang H. National and provincial impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in China: a modeling analysis. BMC Med. 2021 Aug 11;19(1):181. doi: 10.1186/s12916-021-02049-7. PMID: 34376214; PMCID: PMC8356460. Yu W, Lu M, Wang H, Rodewald L, Ji S, Ma C, Li Y, Zheng J, Song Y, Wang M, Wang Y, Wu D, Cao L, Fan C, Zhang X, Liu Y. Routine immunization services costs and financing in China, 2015. Vaccine. 2018 May 17;36(21):3041-3047. doi: 10.1016/j.vaccine.2018.04.008. Epub 2018 Apr 20. PMID: 29685593. Hart RJ, Stevenson MD, Smith MJ, LaJoie AS, Cross K. Cost-effectiveness of Strategies for Offering Influenza Vaccine in the Pediatric Emergency Department. JAMA Pediatr. 2018 Jan 2;172(1):e173879. doi: 10.1001/jamapediatrics.2017.3879. Epub 2018 Jan 2. PMID: 29114729; PMCID: PMC6583269. Yang J, Jit M, Zheng Y, Feng L, Liu X, Wu JT, Yu H. The impact of influenza on the health related quality of life in China: an EQ-5D survey. BMC Infect Dis. 2017 Oct 16;17(1):686. doi: 10.1186/s12879-017-2801-2. PMID: 29037172; PMCID: PMC5644056. Prosser LA, Payne K, Rusinak D, Shi P, Uyeki T, Messonnier M. Valuing health across the lifespan: health state preferences for seasonal influenza illnesses in patients of different ages. Value Health. 2011 Jan;14(1):135-43. doi: 10.1016/j.jval.2010.10.026. PMID: 21211495. Yang S, Wang Q, Li T, Long J, Xiong Y, Feng L, Wang Q, Zhao Y, Yang J, Tang W, Zhang H, Qi L. Effectiveness of influenza vaccine among the population in Chongqing, China, 2018-2022: A test negative design-based evaluation. Hum Vaccin Immunother. 2024 Dec 31;20(1):2376821. doi: 10.1080/21645515.2024.2376821. Epub 2024 Jul 18. PMID: 39025479; PMCID: PMC11259055. Procter SR, Waterlow NR, Radhakrishnan S, van Leeuwen E, Meeyai A, Cooper BS, Chuenkitmongkol S, Teerawattananon Y, Eggo RM, Jit M. Health impact and cost-effectiveness of vaccination using potential next-generation influenza vaccines in Thailand: a modelling study. BMJ Glob Health. 2024 Nov 18;9(11):e015837. doi: 10.1136/bmjgh-2024-015837. PMID: 39557448; PMCID: PMC11574519. Barbieri E, Wang Y, Cantarutti A, Scamarcia A, Cantarutti L, Corrao G, Torbica A, Giaquinto C. Cost-Effectiveness of Influenza Vaccination in Healthy Children: A 10-Year Population-Based Study. Vaccines (Basel). 2024 Sep 28;12(10):1113. doi: 10.3390/vaccines12101113. PMID: 39460280; PMCID: PMC11511569. Brydak L, Roiz J, Faivre P, Reygrobellet C. Implementing an influenza vaccination programme for adults aged ≥65 years in Poland: a cost-effectiveness analysis. Clin Drug Investig. 2012 Feb 1;32(2):73-85. doi: 10.2165/11594030-000000000-00000. PMID: 22201294. Postma MJ, Bos JM, van Gennep M, Jager JC, Baltussen R, Sprenger MJ. Economic evaluation of influenza vaccination. Assessment for The Netherlands. Pharmacoeconomics. 1999;16 Suppl 1:33-40. doi: 10.2165/00019053-199916001-00005. PMID: 10623374. Hassan MZ, Jubayer Biswas MAA, Shirin T, Rahman M, Chowdhury F, Azziz-Baumgartner E, Davis WW, Hussain M. Cost-effectiveness of seasonal influenza vaccination in WHO-defined high-risk populations in Bangladesh. J Glob Health. 2024 Jul 19;14:04126. doi: 10.7189/jogh.14.04126. PMID: 39024624; PMCID: PMC11257706. Salo H, Kilpi T, Sintonen H, Linna M, Peltola V, Heikkinen T. Cost-effectiveness of influenza vaccination of healthy children. Vaccine. 2006 Jun 5;24(23):4934-41. doi: 10.1016/j.vaccine.2006.03.057. Epub 2006 Apr 7. PMID: 16678945. Newall AT, Scuffham PA, Kelly H, Harsley S, Macintyre CR. The cost-effectiveness of a universal influenza vaccination program for adults aged 50-64 years in Australia. Vaccine. 2008 Apr 16;26(17):2142-53. doi: 10.1016/j.vaccine.2008.01.050. Epub 2008 Feb 20. PMID: 18343537. Aballéa S, De Juanes JR, Barbieri M, Martin M, Chancellor J, Oyagüez I, Verwee B, Largeron N. The cost effectiveness of influenza vaccination for adults aged 50 to 64 years: a model-based analysis for Spain. Vaccine. 2007 Sep 28;25(39-40):6900-10. doi: 10.1016/j.vaccine.2007.07.033. Epub 2007 Aug 6. PMID: 17764790.. Jackson LA, Jackson ML, Nelson JC, Neuzil KM, Weiss NS. Evidence of bias in estimates of influenza vaccine effectiveness in seniors. Int J Epidemiol. 2006 Apr;35(2):337-44. doi: 10.1093/ije/dyi274. Epub 2005 Dec 20. PMID: 16368725. Rothberg MB, Rose DN. Vaccination versus treatment of influenza in working adults: a cost-effectiveness analysis. Am J Med. 2005 Jan;118(1):68-77. doi: 10.1016/j.amjmed.2004.03.044. PMID: 15639212. Lee PY, Matchar DB, Clements DA, Huber J, Hamilton JD, Peterson ED. Economic analysis of influenza vaccination and antiviral treatment for healthy working adults. Ann Intern Med. 2002 Aug 20;137(4):225-31. doi: 10.7326/0003-4819-137-4-200208200-00005. PMID: 12186512. Devlin N, Parkin D. Does NICE have a cost-effectiveness threshold and what other factors influence its decisions? A binary choice analysis. Health Economics 2004; 13:437-52; PMID:15127424. George B, Harris A, Mitchell A. Cost effectiveness analysis and the consistency of decision making - Evidence from pharmaceutical reimbursement in Australia (1991 to 1996). Pharmacoeconomics 2001; 19:1103-9; PMID:11735677. Bridges JFP, Onukwugha E, Mullins CD. Healthcare Rationing by Proxy Cost-Effectiveness Analysis and the Misuse of the $50 000 Threshold in the US. Pharmacoeconomics 2010; 28:175-84; PMID:20067332. Xu J, Zhou F, Reed C, Chaves SS, Messonnier M, Kim IK. Cost-effectiveness of seasonal inactivated influenza vaccination among pregnant women. Vaccine. 2016 Jun 8;34(27):3149-3155. doi: 10.1016/j.vaccine.2016.04.057. Epub 2016 May 6. PMID: 27161997; PMCID: PMC8721743. Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, Kuntz KM, Meltzer DO, Owens DK, Prosser LA, Salomon JA, Sculpher MJ, Trikalinos TA, Russell LB, Siegel JE, Ganiats TG. Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016 Sep 13;316(10):1093-103. doi: 10.1001/jama.2016.12195. Erratum in: JAMA. 2016 Nov 8;316(18):1924. doi: 10.1001/jama.2016.15518. PMID: 27623463. Avritscher EB, Cooksley CD, Geraci JM, Bekele BN, Cantor SB, Rolston KV, Elting LS. Cost-effectiveness of influenza vaccination in working-age cancer patients. Cancer. 2007 Jun 1;109(11):2357-64. doi: 10.1002/cncr.22670. PMID: 17457827. Maciosek MV, Solberg LI, Coffield AB, Edwards NM, Goodman MJ. Influenza vaccination health impact and cost effectiveness among adults aged 50 to 64 and 65 and older. Am J Prev Med. 2006 Jul;31(1):72-9. doi: 10.1016/j.amepre.2006.03.008. PMID: 16777545. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5969159","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":412536998,"identity":"42a03be0-86d9-48a3-900b-a6dbde28f07e","order_by":0,"name":"Zilian Yu","email":"","orcid":"","institution":"Yinzhou district center for disease control and prevention","correspondingAuthor":false,"prefix":"","firstName":"Zilian","middleName":"","lastName":"Yu","suffix":""},{"id":412537000,"identity":"3746a6f9-b66e-468d-9368-f03b9a13bd20","order_by":1,"name":"Changzheng Jiang","email":"","orcid":"","institution":"Yinzhou district center for disease control and prevention","correspondingAuthor":false,"prefix":"","firstName":"Changzheng","middleName":"","lastName":"Jiang","suffix":""},{"id":412537002,"identity":"0093b067-53c9-40a3-9708-93a675af3e71","order_by":2,"name":"Junfeng Zhang","email":"","orcid":"","institution":"Yinzhou district center for disease control and prevention","correspondingAuthor":false,"prefix":"","firstName":"Junfeng","middleName":"","lastName":"Zhang","suffix":""},{"id":412537005,"identity":"d150bbda-e36f-404d-ac1b-38899369565b","order_by":3,"name":"Yi Xiang","email":"","orcid":"","institution":"Yinzhou district center for disease control and prevention","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Xiang","suffix":""},{"id":412537008,"identity":"ed03e0a9-a58d-4dbc-97c1-335f8b4edc6c","order_by":4,"name":"Yu Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAnklEQVRIiWNgGAWjYBACAyA+wFAhISdPopYzFsaGDaRoYWBsq0gEaiQSmEukPzzMO08igbGB+eGjG8RosZyRY3Bw5jaJPHYGNmPjHKIcdiOH4cDHbRLFjA08bNJEakl/cCBxjkRiwwHitSQYHPjYQJKWM28MDs44JmFs2Ey0X46nP/7MU1MnJ8/e/PAxUVoQgJk05aNgFIyCUTAK8AEAu6Qxnx5T5esAAAAASUVORK5CYII=","orcid":"","institution":"Zhejiang Center for Disease Control and Prevention","correspondingAuthor":true,"prefix":"","firstName":"Yu","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2025-02-06 01:53:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5969159/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5969159/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75900012,"identity":"69bb9350-603e-450b-bc54-b39631ef6996","added_by":"auto","created_at":"2025-02-10 10:59:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":162549,"visible":true,"origin":"","legend":"\u003cp\u003eAnnul influenza vaccination cost-effectiveness simulation model\u003c/p\u003e","description":"","filename":"FIGURE1.png","url":"https://assets-eu.researchsquare.com/files/rs-5969159/v1/6026534799eb474443826967.png"},{"id":75898060,"identity":"7ba755ee-31a0-4fd3-a398-90938afb2b1c","added_by":"auto","created_at":"2025-02-10 10:43:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":154497,"visible":true,"origin":"","legend":"\u003cp\u003eOne-way sensitivity analysis for vaccination compared to no vaccination for adults aged 18-49 years with non-high risk status. Base-case= $9705 /QALY gained\u003c/p\u003e","description":"","filename":"FIGURE2.png","url":"https://assets-eu.researchsquare.com/files/rs-5969159/v1/f96dad306e566075dcf6ade5.png"},{"id":75900014,"identity":"7756d198-4745-446a-967d-be3503dba59a","added_by":"auto","created_at":"2025-02-10 10:59:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":152378,"visible":true,"origin":"","legend":"\u003cp\u003eOne-way sensitivity analysis for vaccination compared to no vaccination for adults aged 18-49 years with high risk status. Base-case= $4385 /QALY gained\u003c/p\u003e","description":"","filename":"FIGURE3.png","url":"https://assets-eu.researchsquare.com/files/rs-5969159/v1/d269c423f25080a16062e945.png"},{"id":75898058,"identity":"dde4b7af-5e6a-4711-b7ac-d3d754c48eeb","added_by":"auto","created_at":"2025-02-10 10:43:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":136066,"visible":true,"origin":"","legend":"\u003cp\u003eProbabilistic sensitivity analyses for non-high risk groups\u003c/p\u003e","description":"","filename":"FIGURE4.png","url":"https://assets-eu.researchsquare.com/files/rs-5969159/v1/e15ae14ed4477305b8044d1f.png"},{"id":75898061,"identity":"e55e3864-45bb-43f6-8957-675586770d2d","added_by":"auto","created_at":"2025-02-10 10:43:53","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":155295,"visible":true,"origin":"","legend":"\u003cp\u003eProbabilistic sensitivity analyses for high risk groups\u003c/p\u003e","description":"","filename":"FIGURE5.png","url":"https://assets-eu.researchsquare.com/files/rs-5969159/v1/71752121c087375df9bf80a5.png"},{"id":77645487,"identity":"3e858cbc-cf36-4e9f-adbd-c8d0e12dded5","added_by":"auto","created_at":"2025-03-03 23:31:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1801459,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5969159/v1/beb4d3f0-c6f8-4dcf-b0c6-38ddaad1753d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-effectiveness of annual trivalent inactivated influenza vaccine program by age and risk status","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eInfluenza circulates annually and causes substantial morbidity and mortality, with the highest burden in adults aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years and children aged\u0026thinsp;\u0026lt;\u0026thinsp;5 years. Influenza caused 3\u0026ndash;5\u0026nbsp;million severe cases and 290,000-650,000 deaths throughout the world annually[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most of the influenza related deaths or hospitalizations occurred in elders aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years and children aged\u0026thinsp;\u0026lt;\u0026thinsp;5 years[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. A meta analysis from mainland China found the influenza-related outpatient visit rate ranged from 0.1 to 7.4 per 1000 persons[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The influenza-related hospitalization rates were also higher among children and adolescents, with 384 per 100,000 children aged\u0026thinsp;\u0026lt;\u0026thinsp;5 years and 112 per 100,000 children aged\u0026thinsp;\u0026lt;\u0026thinsp;15 years[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The influenza-related all-age mortality was 23 per 100,000 persons and the mortality among adults aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years was significantly higher than that for those aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVaccine is one of most effective inters to prevent influenza. Almost one-third of the World Health Organization (WHO) Member States recommended influenza vaccination for the entire population or persons with high risk[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Influenza vaccination had been incorporated into the national immunization program (NIP) of many developed countries and some upper middle-income countries. Vaccination programs in mainland China are categorized into NIP and non-NIP. The former are free of charge but mandatory, while the latter, including influenza vaccine, are self-funded and optional. Since the current self-paid policy, the coverage of influenza vaccination for all-age population is extremely low remaining around 2%[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Chinese vaccine administration law, which was issued in 2019, recommended the gradual incorporation of self-funded vaccines into NIP. In the transitional period, local health authorities were encouraged to introduce new vaccines into the local immunization program and release the free-administration policy before NIP policy at national level. Currently, Zhejiang province provide the trivalent inactivated influenza vaccine (IIV3) to adults aged\u0026thinsp;\u0026gt;\u0026thinsp;70 years and it could significantly improve the vaccination coverage from 2\u0026ndash;37%. A government-funded influenza vaccination policy could not only reduce the disease burden by improving vaccination coverage, but also would improve public trust in vaccines[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince the 2009 pandemic influenza A(H1N1) virus circulated as one of the seasonal influenza viruses, the epidemiologic characteristic of seasonal influenza had been changed[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Prior to 2009, influenza A/H3 predominant seasons were associated with more severe influenza-related health outcomes, but a recent epidemiologic study on influenza observed higher incidence of influenza illness in working-age adults[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Moreover, the surveillance data suggested that younger working-age adults now experience more severe influenza related illness during influenza A/H1 predominant seasons rather than influenza A/H3 predominant seasons[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Since the 2009 pandemic influenza A influenza(H1N1) strain is now circulating as part of the set of seasonal influenza viruses, the pattern of vaccine-averted influenza events across age and risk strata may differ.\u003c/p\u003e \u003cp\u003eSince 2010, the Advisory Committee on Immunization Practices (ACIP) implemented a universal influenza vaccination recommendation for all persons aged\u0026thinsp;\u0026ge;\u0026thinsp;6 months and encouraged the use of more convenient settings to improve the coverage and reduce the cost[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Given the changes in recommendations from the latest Chinese vaccine administration law and the changes in the epidemiology of influenza, many public health authorities and experts are calling for the influenza vaccine included into NIP, providing free vaccination for all-age group aged\u0026thinsp;\u0026ge;\u0026thinsp;6 months. Importantly, a cost-effectiveness evaluation is needed to inform decision-makers of whether to publicly fund influenza vaccination at local level. Policy decisions at various levels are driven by the uncertainties on disease burden, the unclear picture of demographic structure and socioeconomic level. Hence, the objective of this study was to evaluate the health and economic outcomes related to annual IIV3 program for population aged\u0026thinsp;\u0026ge;\u0026thinsp;6 months by age and risk status based on the new evidence and under the context of Zhejiang province.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design\u003c/h2\u003e \u003cp\u003eThe state-transition simulation model was applied to assessing the health and economic outcomes for annul influenza vaccination. The hypothetical cohorts used in this study were constructed based on the 7th census data in 2020, which could reflect the differences in the influenza epidemiologic characteristics and vaccine effectiveness and would accurately estimate the cost-effectiveness of vaccination among different cohorts. Specifically, the general population were stratified by age as follow: 6 months-4 years, 5\u0026ndash;17 years, 18\u0026ndash;49 years, 50\u0026ndash;64 years and \u0026ge;\u0026thinsp;65 years. Each cohort (age group) was further stratified by risk status as defined by China center for disease control and prevention (CDC): those at higher risk for influenza-related complications (\u0026lsquo;high risk\u0026rsquo;) or not (\u0026lsquo;non-high-risk\u0026rsquo;)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Besides, cohort aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years were all assumed as high risk for influenza-related complications. Finally, there were 9 separate subgroups for the data analysis. The time horizon was set to one year as most influenza cases and complications occurred within a single influenza season (6 months). Permanent outcomes, such as death and sequela following influenza-related hospitalization, were included for the duration of a lifetime. This study was performed from a societal perspective and all model input parameters were derived from published sources, supplemented by expert input where data were scarce. The model was programmed using TreeAge Pro 2019 software.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Model construction\u003c/h2\u003e \u003cp\u003eFigure 1 represented the simulation model, including influenza- and vaccination- related health states. During a given year, a person could experience uncomplicated influenza, influenza-related outpatient visit, influenza-related hospitalization, influenza-related death or no influenza-related health event. For those with an influenza-related hospitalization, some would also experience sequelae associated with influenza. For person been vaccinated, vaccination-related adverse reaction, like injection site reaction and systematic reaction were also included.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Vaccination strategy\u003c/h2\u003e \u003cp\u003eThe vaccination strategy in the model was providing a free IIV3 for all-age group aged\u0026thinsp;\u0026ge;\u0026thinsp;6 months. The vaccination program strategy was defined as vaccination with any available influenza vaccine on the market, although there might be more than ten influenza vaccine manufactures in mainland China. Other types of influenza vaccine, such as quadrivalent inactivated influenza vaccine and trivalent live attenuated influenza vaccine, were not considered into our analysis for two reasons. First, there had been no confirmed detections of circulating B/Yamagata lineage viruses since March 2020 globally. Second, the trivalent live attenuated influenza vaccine was only applied for use among individual aged 3\u0026ndash;17 years, not the all-age population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Parameters\u003c/h2\u003e \u003cp\u003eInfluenza-related outcomes included episodes of influenza illness (outpatient visit or not), influenza-related hospitalization (with and without sequelae), and influenza-related death. We assumed that the incidence of influenza illness would not vary with risk status while the probability of complications following influenza would vary by risk status. This hypothesis was made due to insufficient evidence and we want to make a conservative approach to the results. Incidence of influenza illness, outpatient visits, hospitalizations, and death by both age were derived using published data from 2017-18 influenza seasons[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The incidence of outpatient visits by risk status were estimated based on the proportion of high-risk and non-high risk persons reporting care-seeking studies[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The incidence of hospitalization and death by risk status were derived from a study through using the proportion of influenza confirmed hospitalizations with at least one high-risk condition[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The probability of influenza-related sequelae was based on studies on influenza-related neurological complications[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. As the available IIV3 were made by many manufactures in China, we assumed to use an average vaccine effectiveness estimate to reflect all influenza vaccine types and for different age groups, which was derived from the US Flu Vaccine Effectiveness Network[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Vaccination-related adverse events were also assumed to be similar across all vaccine types from different manufactures, including episodes of injection site reactions and systematic reactions. A very small proportion of vaccinee was assumed to die or experience sequelae after vaccination. The incidence of adverse reactions was extracted from published reports[\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProbability parameters in the model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase Case\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of influenza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.04\u0026ndash;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u0026ndash;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\u0026ndash;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\u0026ndash;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u0026ndash;0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of outpatient visit following influenza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64\u0026ndash;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16,17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u0026ndash;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34\u0026ndash;0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.38\u0026ndash;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75\u0026ndash;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.57\u0026ndash;0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.43\u0026ndash;0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.47\u0026ndash;0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u0026ndash;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncidence of hospitalization following influenza (/10000 population)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.49\u0026ndash;11.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16,18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u0026ndash;1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.19\u0026ndash;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.28\u0026ndash;12.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.04-134.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.75\u0026ndash;35.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.55\u0026ndash;48.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.25-104.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.27-205.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncidence of death following influenza (/10000 population)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00-0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16,18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00-0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00-0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y NHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u0026ndash;0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00-2.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00-2.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.09\u0026ndash;4.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34\u0026ndash;7.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.09\u0026ndash;23.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of sequela following influenza-related hospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00-0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine effectiveness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.37\u0026ndash;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.28\u0026ndash;0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\u0026ndash;0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\u0026ndash;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15\u0026ndash;0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of injection site reaction following influenza vaccination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u0026ndash;0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000-0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;18y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000-0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of systematic reaction following influenza vaccination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u0026ndash;0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000-0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;18y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000-0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of death following influenza vaccination(/10000 doses)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbability of sequelae following influenza vaccination(/10000 doses)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiscount rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\u0026ndash;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUniform\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNHR: non-high risk; HR: high risk\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCost estimates included direct medical, direct non-medical, and opportunity costs. The cost of self-medication for influenza was derived from a survey in Jiangsu Province, China [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The cost of outpatient and hospitalizations were based on a national survey[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The cost of sequelae following influenza vaccination or influenza hospitalization was obtained from a previous study[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Vaccination costs included direct vaccine dose cost, administration service costs, syringe cost, which were derived from a national survey[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Children aged 6\u0026ndash;35 months were given 2 doses of influenza vaccine as recommended China CDC. The cost due to adverse reactions following IIV3 vaccination was obtained from published literature[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The productivity loss was calculated by multiplying the time loss due to influenza illness by the average daily productivity in 2023 in Zhejiang province, only for individual aged 18\u0026ndash;59 years. Where appropriate, unit costs were converted into 2024 US dollars (\u003cspan\u003e$\u003c/span\u003e1\u0026thinsp;=\u0026thinsp;CNY7.10). All costs and utility were adjusted to 2024 values by using the discount rate of 3% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCost parameters in the model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBase Case\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOTC medications for minor influenza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e4.01\u0026ndash;6.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutpatient visit for influenza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e137.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization for influenza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1384.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSequelae following influenza-related hospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e749958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e0-1543176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfluenza vaccine price/dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e2.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSyringe price/dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eService cost/dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e3.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician visit for injection site reaction following influenza vaccination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician visit for systematic reaction following influenza vaccination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost for sequelae following influenza vaccination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e749958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase\u0026thinsp;\u0026plusmn;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLognormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProductivity losses for non-medically attended influenza*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProductivity losses for medically attended influenza*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProductivity losses for influenza-related hospitalization*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.8d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProductivity losses for systematic reaction following influenza vaccination*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDaily productivity*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e52.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLocal data\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*: Productivity losses parameters only for individuals aged 18-59y\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNHR: non-high risk; HR: high risk\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe health utility was assessed by the quality-adjusted life years (QALYs), which were the main measure of health benefits. Health states in the model were primarily temporary except for sequelae or death. Each temporary health state would cause a loss in QALYs that was subtracted from the total QALYs, which were estimated through the discounted life expectancy for every subgroup. The utility weight associated with each health state and the duration of influenza illness were derived from an EQ-5D survey and a trade-off survey of US adults [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. QALYs loss for each health state were calculated by multiplying the utility weight for the health state by the duration of the health state. For example, QALYs loss for permanent sequelae were calculated by multiplying the relevant utility weight by the remaining life expectancy (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuality parameters in the model\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase Case\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAge Weights\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eUtility decrement for influenza illness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.7x\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e7d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e30,31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.0x\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.008\u0026ndash;0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9x\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.6x\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eUtility decrement for hospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.2x\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e11.8d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e30,31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.7x\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u0026ndash;0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.0x\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.5x\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUtility decrement for systematic reaction following influenza vaccination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u0026ndash;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUtility for sequelae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.018\u0026ndash;0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30,31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUtility for death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eLife expectancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.52y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLocal data\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.67y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.37y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.12y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.51y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Data analysis\u003c/h2\u003e \u003cp\u003eThe primary outcome was the incremental cost-effectiveness ratio (ICER), calculated by dividing the discounted net costs by discounted net QALYs. Secondary outcomes included the number of influenza cases averted, hospitalizations averted, deaths averted, adverse reactions occurred, QALYs gained, and net costs. The base-case analysis compared the vaccination program strategy to no vaccination using the societal perspective. One-way sensitivity analyses were conducted for most parameters among cohort aged 18\u0026ndash;49 years by different risk status, in which each parameter value was varied over a plausible range to determine the impact from each parameter on the ICER. The plausible ranges were estimated by using confidence intervals (CI) from relevant studies or \u0026plusmn;\u0026thinsp;20% of base values if the confidence interval was not available. Probabilistic sensitivity analysis (PSA) was also implemented to assess the effects of parameter uncertainty by defining parameters using a distribution of possible values and running the model for 10,000 iterations to derive 95% CI.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Base-case analysis\u003c/h2\u003e \u003cp\u003eThe results of base-case analysis were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The number of influenza cases averted compared to no vaccination varied by age but was highest for children aged from 6 months to 4 years, with 60 influenza cases averted per 1000 vaccinated. The avert case number did not varied by risk status as we assumed the probability of influenza illness was the same among different risk status. On the other hand, the number averted hospitalization and death varied with age group and risk status. Hospitalizations averted were highest among children aged from 6 months to 4 years (2.89 hospitalizations averted per 1000 vaccinated), followed by older persons aged\u0026thinsp;\u0026ge;\u0026thinsp;65 yeas (2.04 hospitalizations averted per 1000 vaccinated). The number of averted deaths were highest for older persons aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years, with 0.22 deaths averted per 1000 vaccinated.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProjected net costs health benefits and risks of influenza vaccination by age and risk status (per 1000 vaccinated)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNet cost\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQALYs gained\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases averted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHospitalizations averted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDeaths averted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAdverse events incurred\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eNon-high risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e11260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e10205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e9705\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e6268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e4385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e2207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003cspan\u003e$\u003c/span\u003e904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe incidence of adverse reactions related to influenza vaccine was highest among children aged from 6 months to 4 years, with 21 adverse reactions occurred per 1000 vaccinated. The incidence also did not vary between different risk status as we assumed its probability was same.\u003c/p\u003e \u003cp\u003eBased on 1000 persons being vaccinated, annual influenza vaccination strategy was to be cost-saving for older persons aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years with high-risk status. The net cost of annual influenza vaccination for other subgroups ranged from \u003cspan\u003e$\u003c/span\u003e2207 per 1000 vaccinated for adults aged 50\u0026ndash;64 years to \u003cspan\u003e$\u003c/span\u003e11260 per 1000 vaccinated for children aged from 6 months to 4 years.\u003c/p\u003e \u003cp\u003eAnnual influenza vaccination could yield net positive QALYs for all subgroups, indicating health benefits of vaccination exceeded the risk of adverse reactions related to vaccine. The net QALYs gained were highest for children aged from 6 months to 4 years with high risk status (4.1 QALYs per 1000 vaccinated), followed by older persons aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years with high-risk status (3.9 QALYs per 1000 vaccinated).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e indicated the ICER of annual influenza vaccination varied by age and risk status. In non-high risk subgroups, the ICER ranged from \u003cspan\u003e$\u003c/span\u003e6268/QALY (adults aged 50\u0026ndash;64 years) to \u003cspan\u003e$\u003c/span\u003e11260/QALY (children aged from 6 months to 4 years), and was most favorable for adults aged 50\u0026ndash;64 years (\u003cspan\u003e$\u003c/span\u003e6268/QALY). In high risk subgroups, influenza vaccination was cost-saving for adults aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years. For the remaining high-risk subgroups, influenza vaccination yielded ICERs that ranged from \u003cspan\u003e$\u003c/span\u003e2207/QALY (adults aged 50\u0026ndash;64 years) to \u003cspan\u003e$\u003c/span\u003e5260/QALY (children aged from 6 months to 4 years).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncremental cost-effectiveness ratios by age and risk status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e/QALY gained\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e/Cases averted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e/Hospitalizations averted\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e/Deaths averted\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eNon-high risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e11260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e4504\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e187.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e38828\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e10205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e242.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e145786\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e9705\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e4853\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e388.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e194100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e6268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e12536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e120.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e15288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6m-4y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1283\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e87.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1820\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5-17y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e121.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e7187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18-49y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e4385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e175.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e5481\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50-64y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e2207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e42.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan\u003e$\u003c/span\u003e1314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003cspan\u003e$\u003c/span\u003e904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003cspan\u003e$\u003c/span\u003e232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-\u003cspan\u003e$\u003c/span\u003e43.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003cspan\u003e$\u003c/span\u003e443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Sensitivity analyses\u003c/h2\u003e \u003cp\u003eIn one-way sensitivity analyses, the ICERs for influenza vaccination were most sensitive to changes in probability of influenza illness, vaccine effectiveness, probability of systematic reactions for adults aged 18\u0026ndash;49 years with non-high risk status, while were most sensitive to changes in probability of influenza illness, cost of hospitalization, probability of death for adults aged 18\u0026ndash;49 years with high risk status (Fig.\u0026nbsp;2\u0026ndash;3).\u003c/p\u003e \u003cp\u003e Cost-effectiveness acceptability curves were depicted using probabilistic sensitivity analyses (Fig.\u0026nbsp;4). Cost-effectiveness acceptability curves characterize uncertainty in economic evaluations and represent the probability that an intervention is cost-effective under a range of cost-effectiveness thresholds. Under the threshold of \u003cspan\u003e$\u003c/span\u003e5000/QALY, the probability that annual influenza vaccination strategy would range from 7.51% (children aged from 6 months to 4 years) to 81.12% (adults aged 50\u0026ndash;64 years) for non-high risk subgroups, and ranged from 34.32% (children aged from 6 months to 4 years) to 99.87% (older person aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years) for high risk subgroups.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eSeasonal influenza imposes a significant health and economic burden in China, particularly in elders with high risk for severe consequences of infection. We evaluated the cost-effectiveness of annual IIV3 universal vaccination strategy among population aged\u0026thinsp;\u0026ge;\u0026thinsp;6 months, under the Zhejiang province-specific demographic data. The highest benefit of annual IIV vaccination program was observed in elders aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years with high risk, and this strategy could also induce the net health gains for all other subgroups, with net cost incurred simultaneously. In terms of health gains from IIV3, our findings were consistent with results from previous reports[\u003cspan additionalcitationids=\"CR33 CR34 CR35 CR36\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], which demonstrated IIV3 could reducing the number of influenza cases, hospitalizations, and deaths, and being cost saving. Our analysis indicated that the ICER was cost-saving among elders aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years with high risk. We assumed that it would be associated with the high incidence of death or complication due to influenza infection among this vulnerable subgroup and more death or severe cases would be averted from IIV3 vaccination.\u003c/p\u003e \u003cp\u003eInfluenza vaccination strategy required a net investment to produce health benefits for most subgroups in this study. Previous reports had indicated that, comparing with no intervention, IIV3 was cost-effective when used in healthy children, healthy adults aged 50\u0026ndash;64 years and the elderly[\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. In our study, the ICER ranged from \u003cspan\u003e$\u003c/span\u003e6268/QALY to \u003cspan\u003e$\u003c/span\u003e11260/QALY for age groups with non-high risk, and ranged from cost-saving to \u003cspan\u003e$\u003c/span\u003e5260/QALY for age groups with high risk. In 2023, the Gross Domestic Product (GDP) per capita of Zhejiang province was \u003cspan\u003e$\u003c/span\u003e17745, which was higher than the ICERs for all age group with or not with high risk. It demonstrated the annual IIV3 vaccination strategy was still cost-effective if we used one time of the GDP per capita.\u003c/p\u003e \u003cp\u003eThe vaccine effectiveness for elders aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years used in our model was lower than previously assumed[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], which might influence the economic value of influenza vaccination strategy. In the base-case analysis, we found influenza vaccination for elders aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years was cost-saving, assuming the vaccine effectiveness was at 27%. Given the substantial burden of influenza illness in elders, our results provided important information demonstrating influenza vaccination for the older age group even if vaccine effectiveness was lower than previously assumed.\u003c/p\u003e \u003cp\u003eStudies on the cost-effectiveness of influenza vaccination program among healthy working-age (18\u0026ndash;49 years) adults in the China were very limited. Among the small number of health economic studies from other countries, influenza vaccination was generally favorable for this age group[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. However, these reports assumed that the vaccination scenario was in low-cost settings and the outcomes varied. These reports also found that parameters including incidence of influenza, cost of vaccination, vaccination effectiveness, productivity loss and daily productivity would significantly influence the cost-effectiveness results, which were similar with the findings in our analysis.\u003c/p\u003e \u003cp\u003eThe cost-effectiveness thresholds of \u003cspan\u003e$\u003c/span\u003e5000/ QALY for this subgroup were applied in our sensitive analysis, which were lower than the commonly used effectiveness thresholds used in previous studies. For example, the threshold range of GB\u0026euro;20000 to 30000 was considered as cost-effective in a report from Great Britain[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Canadian Agency for Drugs and Technologies in Health used a threshold of CAD\u003cspan\u003e$\u003c/span\u003e50000\u0026ndash;100000 in the pharmaceutical health economics evaluation[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Also, a threshold of US\u003cspan\u003e$\u003c/span\u003e50000 was commonly used in similar studies in US[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. There were several reasons for the difference in the threshold settings. First, it might be due to the lower probability of influenza case and influenza-related complication, underscoring the potential economic value of influenza vaccination in different countries, especially for high-risk individuals. For example, a cost-effectiveness study of influenza vaccination among pregnant women found the influenza vaccination resulted in an ICER of \u003cspan\u003e$\u003c/span\u003e260000/QALY during a very low incidence season[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Second, it would be related to the difference in social and economic development between Zhejiang province and these developed countries.\u003c/p\u003e \u003cp\u003eThe second panel on cost-effectiveness in health and medicine recommended that productivity cost should be included in the numerator of the formula of calculating ICER as a monetary term[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. However, other reports would not include the productivity loss into cost since it would be captured in the QALY loss with influenza health states, and causing double counting if including it as an additional cost[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. However, we assumed that the loss in QALYs associated with influenza only considered the life and adjusted life losses due to the disease itself when these data came from field investigation, which might not include the indirect cost. Moreover, the annual influenza vaccination program would be more attractive from the social perspective if the productivity losses included in the analysis.\u003c/p\u003e \u003cp\u003eThere were several limitations to this study. First, indirect effects of reduced transmission were not included in this study because assumptions about the effectiveness of vaccines to reduce transmission were still uncertain for seasonal influenza. If these indirect effects were included, the results would be more favorable for vaccination. Second, our model did not include family spillover effects of illness, such as the burden of informal caregiving. If these effects were included, the cost-effectiveness of vaccination would also be more favorable. Third, the difference in the probability of experiencing symptomatic influenza among individuals with or without high risk was not considered in this analysis, and if a high risk individual was at greater risk of experiencing symptomatic compared to a non-high risk individual, then vaccination would be more favorable for high risk subgroups. Lastly, the analysis did not include the differences in duration of symptoms and complications from influenza between vaccinated versus unvaccinated individual. If vaccinated individual experienced a shorter duration of illness compared to unvaccinated individual, then vaccination would be more economically attractive.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis study provided the crucial information for policy-makers assessing the universal influenza vaccination recommendation. Our findings indicated that influenza vaccination produces cost-effectiveness ratios that were less than commonly used cost-effectiveness thresholds for all subgroups. After incorporating updated epidemiologic and vaccine effectiveness data, annual influenza vaccination remained cost-effective for all-age and different risk status groups from a societal perspective.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate: This study was exempted for ethics approval as it did not contain any personal information and include no human research participants.\u003c/p\u003e\n\u003cp\u003eClinical Trial: Not applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material: Data was provided within the manuscript.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding:\u0026nbsp;This study was funded by medical and health science and technology project of Zhejiang province\u0026nbsp;(Grant number: 2023KY633).\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: YH and ZY developed the specific study protocol, constructed the model for cost effectiveness analysis. CJ collaborated in the study protocol and in the construction and refinement of the model. JZ and YX contributed to the collection of data required for the input parameters. YH and ZY initiated the study design, supervised the project, and directed the analysis and manuscript writing. All authors had carefully revised the draft of the manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgments: We would like to thank the following representatives of various organizations who formed our local expert panel and participated in our consultative meetings and interviews and contributed technical support and expert opinions.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBudd AP, Beacham L, Smith CB, Garten RJ, Reed C, Kniss K, Mustaquim D, Ahmad FB, Cummings CN, Garg S, Levine MZ, Fry AM, Brammer L. Birth Cohort Effects in Influenza Surveillance Data: Evidence That First Influenza Infection Affects Later Influenza-Associated Illness. 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PMID: 16777545.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Influenza, Vaccination, Cost-effectiveness, Trivalent inactivated influenza vaccine, Risk","lastPublishedDoi":"10.21203/rs.3.rs-5969159/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5969159/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe study was aimed to evaluate the cost-effectiveness of annual trivalent inactivated influenza vaccine (IIV3) under the context of Zhejiang province.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA state transition simulation model was constructed to estimate the health and economic outcomes of IIV3 vaccination compared to no vaccination for hypothetical cohorts of Zhejiang province stratified by age and risk status. Model input parameters were derived from multiple sources. The analysis used societal perspectives and a one-year time horizon, and permanent outcomes were also included. The primary outcome was the incremental cost-effectiveness ratio (ICER), with expression of US dollars per quality adjusted life years (QALYs) gained.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn non-high risk subgroups, the ICER ranged from \u003cspan\u003e$\u003c/span\u003e6268/QALY(adults aged 50\u0026ndash;64 years) to \u003cspan\u003e$\u003c/span\u003e11260/QALY (children aged from 6 months to 4 years). In high risk subgroups, the ICER ranged from cost-saving (adults aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years) to \u003cspan\u003e$\u003c/span\u003e5260/QALY (children aged from 6 months to 4 years). Results were most sensitive to changes in the probability of influenza illness, vaccine effectiveness, probability of systematic reactions for adults aged 18\u0026ndash;49 years with non-high risk status, while were most sensitive to changes in probability of influenza illness, cost of hospitalization, probability of death for the same subgroup.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings indicated the ICERs of annual influenza vaccination varied by age and risk status but was less than one time of the Gross Domestic Product (GDP) per capita of Zhejiang province (\u003cspan\u003e$\u003c/span\u003e17745 in 2023), which remained cost-effective for all-age and different risk status groups from a societal perspective.\u003c/p\u003e","manuscriptTitle":"Cost-effectiveness of annual trivalent inactivated influenza vaccine program by age and risk status","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-10 10:43:48","doi":"10.21203/rs.3.rs-5969159/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"68d7cb15-68f5-4144-9ecd-e725a5e95b84","owner":[],"postedDate":"February 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-03T23:23:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-10 10:43:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5969159","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5969159","identity":"rs-5969159","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}