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South Korea's National Immunization Program administers the quadrivalent influenza vaccine (QIV) to manage seasonal influenza, with a particular focus on the elderly. After reviewing the safety and immune response triggered by the adjuvanted QIV (aQIV) in individuals aged 65 and older, the Ministry of Food and Drug Safety in Korea approved its use. However, the extensive impact of aQIV on public health is yet to be fully understood. This study assessed the cost-effectiveness of replacing QIV with aQIV in South Korean adults aged 65 years and older. A dynamic transmission model, calibrated with national influenza data, was applied to compare the influence of aQIV and QIV on older adults and the broader population throughout a single influenza season. This study considered both the direct and indirect effects of vaccination on the elderly. We derived the incremental cost-effectiveness ratios (ICERs) from quality-adjusted life-years (QALYs) and costs incurred, validated through a probabilistic sensitivity analysis with 5,000 simulations. Findings suggest that transitioning to aQIV from QIV in the elderly would be cost-effective, particularly if aQIV's efficacy reaches or exceeds 56.1%. With an ICER of $29,267/QALY, considerably lower than the $34,998/QALY willingness-to-pay threshold, aQIV presents as a cost-effective option. Thus, implementing aQIV with at least 56.1% efficacy is beneficial from both financial and public health perspectives in mitigating seasonal influenza in South Korea.

Seasonal influenza significantly affects both health and economic costs in children and adults. This narrative review summarizes published cost-effectiveness analyses (CEAs) of cell-based influenza vaccines in children and adults <65 years of age, critically assesses the assumptions and approaches used in these analyses, and considers the role of cell-based influenza vaccines for children and adults. CEAs from multiple countries demonstrated the cost-effectiveness of cell-based quadrivalent influenza vaccines (QIVc) compared with egg-based trivalent/quadrivalent influenza vaccines (TIVe/QIVe). CEA findings were consistent across models relying on different relative vaccine effectiveness (rVE) estimate inputs, with the rVE of QIVc versus QIVe ranging from 8.1% to 36.2% in favor of QIVc. Across multiple scenarios and types of analyses, QIVc was consistently cost-effective compared with QIVe, including in children and adults across different regions of the world.

Introduction: Annual influenza vaccination reduces disease burden but vaccination rates are suboptimal, with persistent disparities among subpopulations. The purpose of this trial is to evaluate multicomponent behavioural economic nudge interventions to clinicians and patients to increase influenza vaccination. This trial also includes an intensification nudge to reduce disparities in vaccination among older adult, primary care patients., Methods: This is a two-part, multisite cluster randomised, pragmatic clinical trial. In the first part, a multicomponent nudge intervention will be tested over approximately 6 months (September 2023-February 2024). The second part consists of a replication trial conducted at an additional site during the following influenza season (September 2024-February 2025). Primary care clinics will be randomised to the nudge intervention or usual care. Eligible clinicians and patients at intervention clinics will receive the intervention, and patients deemed high risk for not receiving a vaccine will be further randomised to receive an intensification nudge. The primary outcome is vaccine completion during the eligible visit and the secondary outcome is vaccine completion within 3 months of the eligible visit., Analysis: The effect of the clinic-level nudge intervention on the primary and secondary outcomes will be evaluated using generalised estimating equations (GEEs) with a clinic-level exchangeable working correlation to account for clustering of observations within the clinic. GEE models with an independent working correlation will be used to evaluate the impact of the additional intensification nudge on the primary and secondary outcomes., Ethics and Dissemination: The University of Pennsylvania Institutional Review Board (IRB) approved this trial and serves as the single IRB of record (IRB #851838). Results will be disseminated via peer-reviewed publication and conference presentations., Trial Registration Number: NCT06057727., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Thailand was one of the first low- and middle-income countries to publicly fund seasonal influenza vaccines, but the lack of predictability in the timing of epidemics and difficulty in predicting the dominant influenza subtypes present a challenge for existing vaccines. Next-generation influenza vaccines (NGIVs) are being developed with the dual aims of broadening the strain coverage and conferring longer-lasting immunity. However, there are no economic evaluations of NGIVs in Thailand., Methods: We estimated the health impact and cost-effectiveness of NGIVs in Thailand between 2005 and 2009 using a combined epidemiological and economic model. We fitted the model to data on laboratory-confirmed influenza cases and then simulated the number of influenza infections, symptomatic cases, hospitalisations and deaths under different vaccination scenarios based on WHO-preferred product characteristics for NGIVs. We used previous estimates of costs and disability adjusted life years (DALYs) for influenza health outcomes to estimate incremental net monetary benefit, vaccine threshold prices and budget impact., Results: With the current vaccine programme, there were an estimated 61 million influenza infections. Increasing coverage to 50% using improved vaccines reduced infections to between 23 and 57 million, and with universal vaccines to between 21 and 49 million, depending on the age groups targeted. Depending on the comparator, threshold prices for NGIVs ranged from US$2.80 to US$12.90 per dose for minimally improved vaccines and US$24.60 to US$69.90 for universal vaccines., Conclusion: Influenza immunisation programmes using NGIVs are anticipated to provide considerable health benefits and be cost-effective in Thailand. However, although NGIVs might even be cost-saving in the long run, there could be significant budget implications for the Thai government even if the vaccines can be procured at a substantial discount to the maximum threshold price., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: In older populations admitted for diabetes, limited evidence suggests that influenza vaccination protects against hospitalization outcomes., Methods: This study pooled 27,620 hospitalizations recorded for elderly diabetes patients from the Beijing Elderly Influenza Vaccination Information Registration Database (2013-2018) and the Beijing Urban Employee Basic Medical Insurance Database (2013-2018). Generalized linear regression and propensity score matching were conducted to estimate the effects of influenza vaccination on hospitalization outcomes (in-hospital all-cause mortality, readmission, length and costs of hospitalization), adjusting for measurable confounding factors. The low influenza period (May-July) was used as a reference period to adjust for unmeasured confounding factors during the peak influenza period (November-January)., Results: In propensity score matching, influenza vaccination in peak influenza period could reduce the risk of in-hospital death (OR: 0.47[0.22,0.97]) and readmission (OR: 0.70[0.60,0.81]), length of hospitalization (β: -1.32[-1.47, -1.17]) and medical costs (GMR: 0.90[0.88,0.92]). After adjusting for unmeasured confounding factors, influenza vaccination was associated with 17% (ratio of ORs: 0.83 [0.69, 1.02]) lower risk of readmission and shorter length of hospitalization (difference in β: -0.23 [-0.62, 0.16]). The subgroup analyses showed that male patients with older age and poorer health conditions could benefit more after influenza vaccination., Conclusion: Influenza vaccination could significantly improve hospitalization outcomes in elderly diabetic patients. This provides evidence supporting free influenza vaccination policies for vulnerable populations in low- and middle-income countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite the substantial global impact of influenza, there are limited economic data to guide influenza vaccination programs investments in middle-income countries. We measured the costs of influenza and the costs of an influenza vaccination program in Armenia, using a societal perspective., Methods: During December 2022 through March 2023, retrospective cost data were collected from case-patients and healthcare providers through structured questionnaires at 15 healthcare facilities selected through stratified sampling. Medical costs included medications, laboratory costs, laboratory and diagnostic tests, and routine health care service costs and direct and indirect societal costs were included. Vaccination program costs from the 2021-2022 influenza season were identified using accounting records and categorized as: planning, distribution, training, social mobilization and outreach, supervision and monitoring, procurement, and national- and facility-level administration and storage., Results: The mean costs per episode for SARI and ILI case-patients were $US 823.6 and $US 616.57, respectively. Healthcare service costs were the largest direct expenses for ILI and SARI case-patients. Total costs of the 2021-2022 influenza vaccination program to the government were $US 4,353,738, with the largest costs associated with national- and facility-level administration and storage (30% and 65% respectively). The total cost per dose administered was $US 25.61 ($US 7.73 per dose for procurement and $US 17.88 for the marginal administration cost per dose)., Conclusions: These data on the costs of seasonal influenza prevention programs and the societal costs of influenza illness in Armenia may inform national vaccine policy decisions in Armenia and may be useful for other middle-income countries. Influenza vaccines, like other vaccine programs, are recognized as substantially contributing to the reduction disease burden and associated mortality and further driving economic growth. However, a formal cost-effectiveness analysis should be performed once burden of disease data are available., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP's preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults., Methods: We used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18-64 years old. Model inputs included 2018-2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019-2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season., Results: Among adults ages 18-64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50-64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18-64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18-64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50-64-year-olds., Conclusions: While RIV4 was effective and cost-effective relative to SD-IIV4 for both 50-64-year-old and 18-64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18-64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50-64 year olds) to maximize their cost-benefit ratios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jonathan M Raviotta reports financial support was provided by Sanofi Pasteur Inc. Richard K Zimmerman reports a relationship with Sanofi Pasteur Inc that includes: funding grants. Mary Patricia Nowalk reports a relationship with Sanofi Pasteur Inc that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: During November 2019-October 2021, a pediatric influenza vaccination demonstration project was conducted in four sub-counties in Kenya. The demonstration piloted two different delivery strategies: year-round vaccination and a four-month vaccination campaign. Our objective was to compare the costs of both delivery strategies., Methods: Cost data were collected using standardized questionnaires and extracted from government and project accounting records. We reported total costs and costs per vaccine dose administered by delivery strategy from the Kenyan government perspective in 2021 US$. Costs were separated into financial costs (monetary expenditures) and economic costs (financial costs plus the value of existing resources). We also separated costs by administrative level (national, regional, county, sub-county, and health facility) and program activity (advocacy and social mobilization; training; distribution, storage, and waste management; service delivery; monitoring; and supervision)., Results: The total estimated cost of the pediatric influenza demonstration project was US$ 225,269 (financial) and US$ 326,691 (economic) for the year-round delivery strategy (30,397 vaccine doses administered), compared with US$ 214,753 (financial) and US$ 242,385 (economic) for the campaign strategy (25,404 doses administered). Vaccine purchase represented the largest proportion of costs for both strategies. Excluding vaccine purchase, the cost per dose administered was US$ 1.58 (financial) and US$ 5.84 (economic) for the year-round strategy and US$ 2.89 (financial) and US$ 4.56 (economic) for the campaign strategy., Conclusions: The financial cost per dose was 83% higher for the campaign strategy than the year-round strategy due to larger expenditures for advocacy and social mobilization, training, and hiring of surge staff for service delivery. However, the economic cost per dose was more comparable for both strategies (year-round 22% higher than campaign), balanced by higher costs of operating equipment and monitoring activities for the year-round strategy. These delivery cost data provide real-world evidence to inform pediatric influenza vaccine introduction in Kenya., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Seasonal influenza epidemics result in high levels of healthcare utilization. Vaccination is an effective strategy to reduce the influenza-related burden of disease. However, reporting vaccine effectiveness does not convey the population impacts of influenza vaccination. We aimed to calculate the burden of influenza-related hospitalizations and emergency department (ED) attendance averted by influenza vaccination in Victoria, Australia, from 2017 to 2019, and associated economic savings. We applied a compartmental model to hospitalizations and ED attendances with influenza-specific, and pneumonia and influenza (P&I) with the International Classification of Diseases, 10 th Revision, Australian Modification (ICD-10-AM) diagnostic codes of J09-J11 and J09-J18, respectively. We estimated an annual average of 7657 (120 per 100000 population) hospitalizations and 20560 (322 per 100000 population) ED attendances over the study period, associated with A$85 million hospital expenditure. We estimated that influenza vaccination averted an annual average of 1182 [range: 556 - 2277] hospitalizations and 3286 [range: 1554 - 6257] ED attendances and reduced the demand for healthcare services at the influenza season peak. This equated to approximately A13 [range: A6 - A25] million of savings over the study period. Calculating the burden averted is feasible in Australia and auseful approach to demonstrate the health and economic benefits of influenza vaccination.

Purpose: Influenza infection induces cardiovascular events in heart failure (HF) patients, with potential risk reduction through vaccination. This study aims to evaluate the cost-effectiveness of influenza vaccination for HF patients in China., Methods: We developed a Markov model with a 3-month cycle to simulate the cost-effectiveness of administering the influenza vaccine to patients with HF over a 3-year period. Patients in the model received either the influenza vaccine or a placebo, in addition to standard HF treatment. Cost data, sourced from the China Healthcare Statistic Yearbook and other public records, and effectiveness data from the IVVE (Influenza Vaccine to Prevent Adverse Vascular Events in HF) trial, were incorporated. Specifically, the cost of the influenza vaccine was 75 Chinese Yuan (CNY) (11 USD), the cost of hospitalization for heart failure (HHF) was 9,326 CNY (1,386 USD), and the cost of treatment for pneumonia was 5,984 CNY (889 USD). The study's primary outcome, the incremental cost-effectiveness ratio (ICER), quantifies the incremental cost (CNY and USD) per incremental quality-adjusted life year (QALY). Additional outcomes included total cost, total effectiveness, incremental cost, and incremental effectiveness. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess certainty and uncertainty, respectively. Scenario analysis, considering various situations, was performed to evaluate the robustness of the results., Results: In the base case analysis, influenza vaccine, compared to placebo, among Chinese HF patients, resulted in a cost increase from 21,004 CNY (3,121 USD) to 21,062 CNY (3,130 USD) and in QALYs from 1.89 to 1.92 (2.55 life years vs. 2.57 life years) per patient. The resulting ICER was 2,331 CNY (346 USD) per QALY [2,080 CNY (309 USD) per life year], falling below the willingness-to-pay threshold based on per capita GDP. One-way sensitivity analysis revealed that disparities in HHF and cardiovascular death rates between groups had the most significant impact on the ICER, while the cost of vaccines had a marginal impact. PSA and scenario analysis collectively affirmed the robustness of our findings., Conclusion: This study suggests that adding the influenza vaccine to standard treatment regimens for Chinese patients with HF may represent a highly cost-effective option. Further real-world data studies are essential to validate these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Liu, Wang and Chen.)

Background: Bangladesh carries a substantial health and economic burden of seasonal influenza, particularly among the World Health Organization (WHO)-defined high-risk populations. We implemented a modelling study to determine the cost-effectiveness of influenza vaccination in each of five high-risk groups (pregnant women, children under five years of age, adults with underlying health conditions, older adults (≥60 years), and healthcare personnel) to inform policy decisions on risk group prioritisation for influenza vaccination in Bangladesh., Methods: We implemented a Markov decision-analytic model to estimate the impact of influenza vaccination for each target risk group. We obtained model inputs from hospital-based influenza surveillance data, unpublished surveys, and published literature (preferentially from studies in Bangladesh, followed by regional and global ones). We used quality-adjusted life years (QALY) as the health outcome of interest. We also estimated incremental cost-effectiveness ratios (ICERs) for each risk group by comparing the costs and QALY of vaccinating compared to not vaccinating each group, where the ICER represents the additional cost needed to achieve one year of additional QALY from a given intervention. We considered a willingness-to-pay threshold (ICER) of less than one gross domestic product (GDP) per capita as highly cost-effective and of one to three times GDP per capita as cost-effective (per WHO standard). For Bangladesh, this threshold ranges between USD 2462 and USD 7386., Results: The estimated ICERs were USD -99, USD -87, USD -4, USD 792, and USD 229 per QALY gained for healthcare personnel, older adults (≥60), children aged less than five years, adults with comorbid conditions, and pregnant women, respectively. For all risk groups, ICERs were below the WHO willingness-to-pay threshold for Bangladesh. Vaccinating pregnant women and adults with comorbid conditions was highly cost-effective per additional life year gained, while vaccinating healthcare personnel, older adults (≥60), and children under five years were cost-saving per additional life year gained., Conclusions: Influenza vaccination to all target risk groups in Bangladesh would be either cost-saving or cost-effective, per WHO guidelines of GDP-based thresholds., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclosed no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Objectives: To investigate the short-term and long-term effectiveness of different levels of financial incentives on increasing the willingness to vaccinate and vaccine uptake., Methods: A randomized controlled trial was conducted to investigate the effectiveness of financial incentives of three groups with monetary incentives (CNY 20, CNY 40, and CNY 60; 1 CNY = 0.13 EUR) vs. a control group-CNY 0-on influenza vaccine uptake among 720 older adults (≥60 years) in Beijing, China. The primary outcome was vaccine uptake, and the secondary outcomes were intention to vaccinate and length of time to immunization., Results: Financial incentive significantly promoted higher intention to influenza vaccination (120/178 [67.42%] vs. 442/542 [81.55%]; Relative Risk [RR], 1.21; 95% CI, 1.02-1.42) and higher vaccination participation (74/178 [41.57%] vs. 316/542 [58.30%]; RR, 1.39; 95% CI, 1.10-1.75). CNY 60 had the largest impact on the intention to vaccinate (15.00% vs. 13.48% and 13.90%) and vaccination uptake (19.42% vs. 14.05% and 16.67%) compared with CNY 20 and CNY 40. Time to vaccination was significantly lower among participants receiving incentives than those without ([37.21 days; 95% CI, 34.33-39.99] vs. [48.27 days; 95% CI, 43.47-53.07]; Hazard Ratio [HR] 1.57, 95% CI 1.22-2.03). We found no long-term influence of financial incentives on vaccination decisions in the following year (217/542, 40.04% vs. 65/178, 36.52%; RR 1.08, 95% CI 0.82-1.42)., Discussion: Our study suggests that modest financial incentives will boost short-term influenza vaccination rates and shorten the length of time to immunization in China. No one single-time financial incentive had a long-term effect on future vaccination behaviours or helped establish regular vaccination behaviours., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: We assess the cost-effectiveness of switching from standard-dose quadrivalent influenza vaccination (SD-QIV) to high-dose vaccination (HD-QIV) for Dutch adults aged 60 years and older., Methods: A health-economic model was used to compare the scenario where HD-QIV was implemented compared to the current standard, SD-QIV. This model used a lifetime horizon and assessed the cost-effectiveness from a societal perspective. A recently published meta-analysis was used to incorporate the benefits of HD-QIV, including cardiorespiratory hospitalizations, in analyses considering RCT only or combining RCT and RWE estimates in a scenario analysis., Results: Implementing HD-QIV is cost effective at its list price, with an ICER of €5,400 per QALY gained. The main driver of these results is the prevention of cardiorespiratory hospitalizations. Other public health benefits are the prevention of GP consults and deaths. HD-QIV is highly likely to be cost-effective, reaching a 100% probability of being cost effective at the Dutch willingness-to-pay threshold of €20,000 per QALY., Conclusions: Implementing HD-QIV for adults aged 60 and over within the existing influenza vaccination campaign is highly cost effective. HD-QIV may support alleviating potential capacity issues in Dutch hospitals in the winter respiratory season., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Dr. Maarten J. Postma and Prof. Dr. Cornelis Boersma received grants and honoraria from various pharmaceutical companies, inclusive those developing, producing and marketing influenza vaccines. The other authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Seasonal influenza epidemics have a substantial public health and economic burden, which can be alleviated through vaccination. The World Health Organization (WHO) recommends a 75% vaccination coverage rate (VCR) in: older adults (aged ≥ 65 years), individuals with chronic conditions, pregnant women, children aged 6-24 months and healthcare workers. However, no European country achieves this target in all risk groups. In this study, potential public health and economic benefits achieved by reaching 75% influenza VCR was estimated in risk groups across four European countries: France, Italy, Spain, and the UK., Methods: A static epidemiological model was used to estimate the averted public health and economic burden of increasing the 2021/2022 season VCR to 75%, using the efficacy data of standard-dose quadrivalent influenza vaccine. For each country and risk group, the most recent data on population size, VCR, pre-pandemic influenza epidemiology, direct medical costs and absenteeism were identified through a systematic literature review, supplemented by manual searching. Outcomes were: averted influenza cases, general practitioner (GP) visits, hospitalisations, case fatalities, number of days of work lost, direct medical costs and absenteeism-related costs., Results: As of the 2021/2022 season, the UK achieved the highest weighted VCR across risk groups (65%), followed by Spain (47%), France (44%) and Italy (44%). Based on modelling, the 2021/2022 VCR prevented an estimated 1.9 million influenza cases, avoiding 375,200 GP visits, 73,200 hospitalisations and 38,400 deaths. To achieve the WHO 75% VCR target, an additional 24 million at-risk individuals would need to be vaccinated, most of which being older adults and patients with chronic conditions. It was estimated that this could avoid a further 918,200 influenza cases, 332,000 GP visits, 16,300 hospitalisations and 6,300 deaths across the four countries, with older adults accounting for 52% of hospitalisations and 80% of deaths. An additional €84 million in direct medical costs and €79 million in absenteeism costs would be saved in total, with most economic benefits delivered in France., Conclusions: Older adults represent most vaccine-preventable influenza cases and deaths, followed by individuals with chronic conditions. Health authorities should prioritise vaccinating these populations for maximum public health and economic benefits., (© 2024. The Author(s).)

A website with vaccine information and interactive social media was reported to improve maternal influenza vaccine uptake. This study aimed to evaluate cost-effectiveness of a web-based intervention on influenza vaccine uptake among pregnant women from the perspective of US healthcare providers. A one-year decision-analytic model estimated outcomes in a hypothetical cohort of pregnant women with: (1) website with vaccine information and interactive social media (intervention group), and (2) usual care (usual care group). Primary measures included influenza infection, influenza-related hospitalization, mortality, direct medical cost, and quality-adjusted life-year (QALY) loss. In base-case analysis, intervention group reduced cost (by USD28), infection (by 28 per 1,000 pregnant women), hospitalization (by 1.226 per 1,000 pregnant women), mortality (by 0.0036 per 1,000 pregnant women), and saved 0.000305 QALYs versus usual care group. Relative improvement of vaccine uptake by the intervention and number of pregnant women in the healthcare system were two influential factors identified in deterministic sensitivity analysis. The intervention was cost-effective in 99.5% of 10,000 Monte Carlo simulations (at willingness-to-pay threshold 50,000 USD/QALY). A website with vaccine information and interactive social media to promote influenza vaccination for pregnant women appears to reduce direct medical costs and gain QALYs from the perspective of US healthcare providers.

Introduction: Adults aged ≥ 65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥ 65 years., Methods: An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient-related outcomes in adults aged ≥ 65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, the UK, USA, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa., Results: Thirty-eight studies reported on the economic and humanistic burden of influenza in adults aged ≥ 65 years. Higher direct costs were reported for people at increased risk of influenza-related complications compared to those at low risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms., Conclusion: Despite the limited data identified, results show that influenza exerts a high humanistic and economic burden in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines., (© 2024. The Author(s).)

Objectives: Annually in France, influenza results in over one million GP consultations, around 20,000 hospitalizations, and approximately 9,000 deaths. This study assesses the cost-effectiveness of cell-based quadrivalent influenza vaccine (QIVc) for those under 65, which enhances effectiveness avoiding egg-adaptation, compared to egg-based quadrivalent influenza vaccine (QIVe)., Methods: An age-structured susceptible-exposed-infected-recovered (SEIR) transmission model, calibrated to represent an average influenza season based on French data from 2011 to 2019, integrates a contact matrix estimating intergroup contact rates. Evaluating epidemiological, economic and utility outcomes, the model includes vaccine effectiveness and medical costs from the existing literature and French national data. Adjustments to quality of life due to infection and hospitalization are also included. Uncertainty is explored through scenario and sensitivity analyses., Results: Compared to QIVe, QIVc significantly reduces healthcare utilization and mortality, preventing 49,946 GP consultations, 1,087 hospitalizations, and 231 deaths in France. Despite an initial investment of 7.6 million euros, QIVc achieves a net saving of 12 million euros in healthcare expenditures, making it a dominant cost-saving strategy. Probabilistic sensitivity analyses indicate dominance in 78% of 10,000 simulations., Conclusions: Introducing cell-based influenza vaccines in the French immunization program prevents influenza cases, hospitalizations, death, while reducing costs versus egg-based influenza vaccines.

Background: In 2003, the WHO aimed for a 75% or higher influenza vaccination rate among at-risk populations. However, this target was achieved in a few groups during selected seasons in some European countries, and never in Germany. Adults with underlying conditions (UCs) are a critical negleted group for influenza vaccination. This study aimed to identify data gaps in influenza burden and vaccination coverage among adults under 60 with UCs in Germany and bridge these gaps using real-world data., Material and Methods: We conducted systematic research and analyses using German administrative and claims databases from June 2016 to April 2024. We report on epidemiology, direct care costs, indirect costs from work incapacity, vaccination coverage rates, and describe data gaps., Results: Influenza data for high-risk populations are limited. Comprehensive data on influenza epidemiology and vaccination coverage rates (VCR) is available, though with a delay in data availability. Before and after the pandemic, individuals aged 50-59 had the highest rates of influenza-related hospitalization and ICU admission compared to younger age groups. Across all age groups and seasons, individuals with UC experienced higher rates of medically attended influenza cases, hospitalizations, and healthcare costs, with those aged 35-59 being particularly vulnerable. Vaccine coverage was higher in adults aged 35-59 compared to those aged 18-24, and in females compared to males., Limitations: Discrepancies of vaccination status, limited data availability, and variations among the extent of UCs., Conclusion: In Germany, recent policy measures have mainly targeted those aged 60 and above. While this elderly population experiences the highest disease-related impact, influenza can also lead to substantial healthcare resource utilization (HCRU) and costs in younger populations with chronic UCs; Facilitating vaccination access for this group, such as through pharmacies, is essential. Definition of quantifiable vaccination targets and measures to increase vaccination rates based on these targets are required.

Background: Seasonal influenza outbreaks in France cause a surge in patients, exacerbating the overburdened healthcare system each winter. Older adults are particularly vulnerable to serious events related to influenza. Quadrivalent influenza high dose (QIV HD) vaccines have been developed to offer better clinical protection in older adults, who often exhibit suboptimal immune response to quadrivalent influenza standard dose vaccines (QIV SD). This study aims to evaluate the public health impact and cost-effectiveness of administering HD versus SD vaccines to individuals aged 65+ in France., Methodology: Using a static model and decision-tree approach, the study analyzed health outcomes such as influenza cases, GP (general practitioner) visits, hospitalizations, and mortality; relative vaccine efficacy (rVE) estimates were derived from a pivotal randomized-controlled trial and a meta-analysis comparing HD to SD vaccines. Two approaches were implemented to model hospitalizations (conditional on influenza or not), and analyses on bed occupancy were performed., Results: Results showed that using QIV HD instead of QIV SD during an average influenza season in France led to the prevention of 57,209 additional cases of influenza, 13,704 GP visits, and 764 influenza-related deaths. Moreover, switching to QIV HD resulted in an additional 1,728-15,970 hospitalizations avoided and 15,124-138,367 reduced days of hospitalization depending on the hospitalization approach used. The cost-utility analysis showed a cost per quality-adjusted life year (QALY) gained ranging from 24,020 €/QALY to 5,036 €/QALY., Conclusions: Switching to QIV HD in older adults was shown to be cost-effective, with even greater public health benefits at a higher coverage rate, regardless of the season severity.

Objective: To compare healthcare resource utilization (HCRU) and all-cause medical costs among individuals aged ≥50 years who received influenza and COVID-19 vaccines on the same day and those who received influenza vaccine only., Methods: We conducted a retrospective cohort study leveraging Optum's de-identified Clinformatics DataMart from 8/31/2021 to 7/31/2023. Individuals aged ≥50 years continuously enrolled in health plans for 1 year prior and until 7/31/2023 were included. Two cohorts were formed based on vaccination status between 8/31/2022 and 1/31/2023: co-administered influenza and COVID-19 vaccines (co-admin cohort) and influenza vaccine only (influenza cohort). Associations between vaccination status and all-cause, influenza-related, COVID-related, pneumonia-related, and cardiorespiratory-related hospitalization, outpatient or emergency room visits and all-cause medical costs were estimated by weighted generalized linear models, adjusting for confounding by stabilized inverse probability of treatment weighting., Results: 613,156 (mean age: 71) and 1,340,011 (mean age: 72) individuals were included in the co-admin and influenza cohorts, respectively. After weighting, the baseline characteristics were balanced between cohorts. The co-admin cohort was at statistically significant lower risk of all-cause (RR: 0.95, 95% CI: 0.93-0.96), COVID-19-related (RR: 0.59, 95% CI: 0.56-0.63), cardiorespiratory-related (RR: 0.94, 95% CI: 0.93-0.96) and pneumonia-related (RR: 0.86, 95% CI: 0.83-0.90) hospitalization but not influenza-related hospitalizations (RR: 0.91, 95% CI: 0.81, 1.04) compared with the influenza cohort. Co-administration was associated with 3% lower all-cause medical cost (cost ratio: 0.974, 95% CI: 0.968, 0.979) during the follow-up period compared to receiving influenza vaccine only., Limitations: Limitations include the potential residual confounding bias in observational data, measurement errors from claims data, and that the cohort was followed for a single season., Conclusion: Receiving co-administered COVID-19 and influenza vaccines versus only receiving influenza vaccination reduced the risk of HCRU, especially COVID-19-related hospitalization and all-cause medical costs. Increasing vaccine coverage, particularly for COVID-19, might have public health and economic benefits.

In Japan, influenza vaccination is offered to children and pregnant women at clinics or hospitals as an elective, self-funded treatment, as the vaccination is not included in the national vaccination subsidy program. However, some Japanese municipalities offer a discretionary subsidy for seasonal influenza vaccination of children and pregnant women as a local policy. We identified these local subsidy programs during 2019/2020 seasonal influenza season by conducting a cross-sectional survey across Japan. Out of a total of 1741 municipalities, responses were received from 1732; therefore, the response rate was 99.5%. The local influenza vaccine subsidy programs for children were offered in 45.7%, and for pregnant women in 10.2%, of Japanese municipalities. This is the first survey of subsidy programs for pregnant women. While policy diffusion of subsidy programs for children was observed during the 9 years since a previous study, such programs for pregnant women remain limited. Despite many municipalities having subsidy programs, we found that their provision still remains limited when viewed as a whole.

Objective: We aimed to determine how municipal subsidies for seasonal influenza vaccines for the elderly affected vaccination coverage and health outcomes and how responses to vaccine prices changed during the COVID-19 pandemic., Study Design and Methods: This ecological study includes 1245 municipalities in Japan between 2019 and 2020. Fixed-effects regression analysis was performed to evaluate the effect of influenza vaccine cost subsidy for people aged 65 years or older on vaccination coverage, all-cause mortality, and influenza-related mortality., Results: The vaccination rate increased when patients' copayments decreased, and reducing the copayment by 1000 Japanese Yen (JPY) was estimated to increase the vaccination rate by 6.3% (95% confidence interval [CI] 4.5-8.2%) in the adjusted model. When examining the additional effect of a zero price compared to a nearly zero price, we found that a zero price increased the immunization rate by 6.4% (95% CI 1.4-11.5%). The effect of copayment on the increase in vaccination coverage was significantly lower during the pandemic than in the pre-pandemic period. The municipal and prefectural analyses found no association between influenza vaccine copayments and all-cause, influenza, or pneumonia mortality., Conclusion: Cost subsidies and the zero-price effect were shown to increase vaccination coverage but were not associated with relevant mortality measures. Although the impact was attenuated under pandemic conditions, cost subsidy effectively increases the vaccination rate., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: China has a high burden of influenza-associated illness among children. We aimed to evaluate the cost-effectiveness of introducing government-funded influenza vaccination to children in China (fully-funded policy) compared with the status quo (self-paid policy)., Methods: A decision tree model was developed to calculate the economic and health outcomes, from a societal perspective, using national- and provincial-level data. The incremental cost-effectiveness ratio (ICER) [incremental costs per quality-adjusted life year (QALY) gained] was used to compare the fully-funded policy with the self-paid policy under the willingness-to-pay threshold equivalent to national and provincial GDP per capita. Sensitivity analyses were performed and various scenarios were explored based on real-world conditions, including incorporating indirect effect into the analysis., Results: Compared to the self-paid policy, implementation of a fully-funded policy could prevent 1,444,768 [95% uncertainty range (UR): 1,203,446-1,719,761] symptomatic cases, 92,110 (95% UR: 66,953-122,226) influenza-related hospitalizations, and 6494 (95% UR: 4590-8962) influenza-related death per season. The fully-funded policy was cost-effective nationally (7964 USD per QALY gained) and provincially for 13 of 31 provincial-level administrative divisions (PLADs). The probability of a funded vaccination policy being cost-effective was 56.5% nationally, and the probability in 9 of 31 PLADs was above 75%. The result was most sensitive to the symptomatic influenza rate among children under 5 years [ICER ranging from - 25,612 (cost-saving) to 14,532 USD per QALY gained]. The ICER of the fully-funded policy was substantially lower (becoming cost-saving) if the indirect effects of vaccination were considered., Conclusions: Introducing a government-funded influenza policy for children is cost-effective in China nationally and in many PLADs. PLADs with high symptomatic influenza rate and influenza-associated mortality would benefit the most from a government-funded influenza vaccination program., (© 2023. National Institute of Parasitic Diseases.)

BACKGROUND: The health and economic benefits of the annual influenza vaccine are well documented, yet vaccination rates in the United States missed the Healthy People 2020 goal and remain a focus of Healthy People 2030 efforts. By identifying underlying reasons for low annual influenza vaccination, social elements that need targeting may be identified and could guide future interventions or policy development to achieve vaccination goals and improve overall public health. OBJECTIVE: To determine the influence of certain social determinants of health on adherence to annual influenza vaccination in American adults. METHODS: This was a retrospective cohort analysis using data from IBM MarketScan Commercial Claims and Encounters Database and national Medicare 5% sample data from 2013 to 2016. Study eligibility criteria included adults (aged 18 years and older) who were continuously enrolled for 3 influenza seasons between 2013 and 2016. Receipt of the influenza vaccine was counted over 3 consecutive influenza seasons, and select social determinants were extracted from publicly available sources. Patient characteristics, health resource utilization, and selected social determinants of health were included in bivariate and multivariate logistic regression analyses to determine their association with annual influenza vaccination. RESULTS: 6,694,571 adults across employer-sponsored and Medicare coverage groups were analyzed, of which 14.7% of Medicare-enrolled adults and 9.2% of commercially enrolled adults were vaccinated in all 3 seasons. Higher proportions of vaccine adherence (ie, all 3 seasons) were observed among females (9.6% vs 8.7% [commercial], 15.0% vs 14.4% [Medicare]), the immunocompromised (11.8% vs 8.3% [commercial], 15.9% vs 13.6% [Medicare]), rural residents (10.5% vs 9.0% [commercial], 15.4% vs 14.6% [Medicare]; all P < 0.0001), and those enrolled in a high-deductible health plan (10.3%). Multivariable logistic regression models indicated that the odds of vaccine adherence tended to be higher in areas of higher poverty (OR=1.012; 95% CI = 1.01-1.02 [commercial], OR=1.01; 95% CI = 1.01-1.01 [Medicare]) yet lower in areas with higher proportions of Democratic voters (OR=0.998; 95% CI = 0.998-0.998 [commercial], OR = 0.996; 95% CI = 0.996-0.997 [Medicare]). Among commercially insured adults, the odds of vaccine adherence were higher in areas of higher health literacy (OR=1.036; 95% CI = 1.036-1.037), but this effect was not observed among Medicare members. Conversely, the odds of vaccine adherence increased as the proportion of those residing in areas of limited Internet access increased (OR=1.007; 95% CI = 1.004-1.010) among Medicare members only. CONCLUSIONS: Key social determinants of health are important factors of vaccine adherence and can guide policy and intervention efforts toward addressing potential hesitancy. A deeper assessment of other contributing social factors is needed in seasonal influenza and other vaccines to better interpret the vaccine-seeking behaviors of adults. DISCLOSURES: This study received no outside funding. Gatwood, Hagemann, Hohmeier, and Chiu declare vaccine-related grant funding from Merck & Co. and GlaxoSmithKline for vaccine research unrelated to the current study. Ramachandran declares vaccine-related grant funding from Glaxo-SmithKline for research unrelated to the current study. Shuvo and Behal have nothing to disclose. Findings described in this study were presented as a poster and podium at the Academy of Managed Care Pharmacy Nexus 2020 Virtual meeting, October 19-23, 2020.

Introduction : Influenza can be a significant public health problem. Nevertheless, it is preventable through vaccination. Concerning the pediatric population, the recommendation of influenza vaccination is under-represented in many European countries. The aim of this systematic review is to evaluate the cost-effectiveness of universal childhood vaccination against influenza in Europe. Areas covered : We conducted a systematic review of original article assessing the cost-effectiveness of influenza vaccination by searching PubMed, Embase and Scopus databases for studies in English, starting from January 1 st , 2010 up to October 21 st , 2020. Expert opinion : Our literature review showed that all studies identified highlight that pediatric vaccinations using a live vaccine, especially in the quadrivalent formulation, are cost-effective compared to current vaccinations (elderly and at-risk groups) with TIV or no vaccination. A significant contribution to this positive economic profile is due to the indirect protection. Already many clinical data report the relevant direct and indirect impact of vaccination against influenza for younger subjects. The recent studies collected in this review showed also that the pediatric vaccination is also cost-effective. Therefore, decision-makers should now consider this new favorable evidence.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare: RR is an employee of the Veterans Health Administration, but the views expressed do not necessarily reflect those of the US Department of Veteran Affairs or the US government. She is a board member for Universities Allied for Essential Medicines North America and the American Medical Student Association Foundation and co-chairs the Doctors for America Drug Affordability Action Team, which is supported by the Laura and John Arnold Foundation. MD and JSR receive research support from the FDA for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation programme. JSR also currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, and from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology, the Agency for Healthcare Research and Quality, the National Heart, Lung and Blood Institute of the National Institutes of Health, and the Laura and John Arnold Foundation. He is an associate research editor at The BMJ. JLS receives research support from the Greenwall Foundation for work related to the topic of this article.

Background: Timely knowledge of which influenza vaccine brands are procured and where is of interest to inform site-selection for brand-specific influenza vaccine effectiveness (VE) studies. Vaccine procurement is a key determinant of brand availability. We therefore sought to understand how the procurement for seasonal influenza vaccine in Europe is organized, how this drives brand availability and how procurement data could enable to determine brand availability pre-season., Methods: Structured telephone interviews were conducted with 15 experts in 16 European countries between 2017 and 2019 to collect information on the influenza vaccine procurement systems. Sources of (brand-specific) procurement data were identified and assessed on public accessibility. Vaccine type and brand availability and timelines were determined for the 2019-20 season to understand how procurement systems drive brand availability and diversity., Results: Four main types of procurement systems for seasonal influenza vaccination campaigns were identified: national public tenders (Croatia, Denmark, Finland, Ireland, Lithuania, Netherlands, Norway, Scotland, Slovenia), regional public tenders (Italy, Spain, Sweden), direct purchase of vaccines by GPs (England, Wales) or pharmacies (Belgium, France, Germany, Greece) from manufacturers or wholesalers. National public tender outcomes are publicly available and timely; brand availability at clinic level can generally be deduced or narrowed down to two brands. Regional tender outcomes are more difficult to find, known very late or not available. In Italian and Spanish regions tenders may be awarded only a few weeks before the seasonal campaign. No public procurement information is available for countries with direct purchase., Conclusion: At the country-level, brand diversity is generally lower for countries with national public tenders than for countries with regional public tenders or direct purchase. In only a few countries, procurement data at the brand level is both publicly available and timely. Therefore the usefulness of procurement data for prospective site-selection for brand-specific VE studies is limited., Competing Interests: MH is an employee of Seqirus. AS is an employee of P95 Epidemiology and Pharmacovigilance. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Pregnant women and new mothers are among the most vulnerable to seasonal influenza; however, little is known about their preferences for flu vaccination. We examined the rural-urban differences in uptake, demand and willingness to pay (WTP) for influenza vaccination among women of childbearing age, to assess the feasibility of implementing locally produced vaccines in Vietnam., Methods: A cross-sectional study was performed in both urban and rural areas of Hanoi in 2018. Socio-demographic characteristics, history of vaccination, demand and WTP for influenza vaccines were obtained. A multivariate logistic regression model was employed to identify the associated factors., Results: Of 750 participants, 29.9% had had flu shots in the current or previous flu season and 64.3% indicated demand for this vaccine. The median of the maximum amount of WTP for influenza vaccination services was US$ 8.5 (IQR: 8.5-17.0). Women living in rural areas had a significantly lower uptake and higher demand, and were willing to pay less than women in urban locations (21.1% vs. 36.6%; 69% vs. 60.2%; and US $8.5 vs. US $11.7, respectively). For urban participants, factors associated with higher demand and WTP for flu shots included having ANC in health facilities and having been vaccinated against influenza in the past; for rural women, these factors were having suffered from influenza and hearing about it., Conclusions: This study informs the feasibility of implementing locally produced influenza vaccines in Vietnam. Educational programs, along with counselling services and government subsidies, should be implemented to improve the coverage, demand and WTP for the vaccine., (© 2020 John Wiley & Sons Ltd.)

Background: Pandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output., Methods: We convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection., Results: Thirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10-2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable., Conclusions: In the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To estimate the general practitioner (GP) consultation rate attributable to influenza in The Netherlands., Methods: Regression analysis was performed on the weekly numbers of influenza-like illness (ILI) GP consultations and laboratory reports for influenza virus types A and B and 8 other pathogens over the period 2003-2014 (11 influenza seasons; week 40-20 of the following year)., Results: In an average influenza season, 27% and 11% of ILI GP consultations were attributed to infection by influenza virus types A and B, respectively. Influenza is therefore responsible for approximately 107 000 GP consultations (651/100 000) each year in The Netherlands. GP consultation rates associated with influenza infection were highest in children under 5 years of age, at 667 of 100 000 for influenza A and 258 of 100 000 for influenza B. Influenza virus infection was found to be the predominant cause of ILI-related GP visits in all age groups except children under 5, in which respiratory syncytial virus (RSV) infection was found to be the main contributor., Conclusions: The burden of influenza in terms of GP consultations is considerable. Overall, influenza is the main contributor to ILI. Although ILI symptoms in children under 5 years of age are most often associated with RSV infection, the majority of visits related to influenza occur among children under 5 years of age., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: The main objective of this study was to estimate the efficacy of influenza vaccination in reducing influenza-attributable hospitalization and emergency room (ER) admission for severe complications and influenza-attributable excess mortality in individuals ≥65 years of age., Methods: We analyzed the ≥65 years-old community (n = 952,822) afferent to the Brescia (Northern Italy) Health Protection Agency, considered an Italian population reference, to evaluate the efficacy of influenza vaccination (seasons 2014-17) in reducing deaths, ER-admissions, and hospitalizations for influenza-related complications in the elderly., Results: A protective effect of influenza vaccination emerged in reducing hospitalization and ER admission for diseases of the respiratory system and for death from all causes in people ≥65 years. The major effect of influenza vaccination was the reduction in risk of death from all causes, increasing with age and comorbidity., Conclusion: Influenza vaccination has reduced the number of ER admissions and hospitalizations caused by influenza-related complications and has prevented death among high-risk groups in elderly ≥65 years, resulting in social and public health cost savings. Stronger or new vaccination strategies are needed to improve vaccination rates among the elderly.

Objectives: As of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 60+ years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of €20 000 per quality-adjusted life-year (QALY)., Methods: An age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of €20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes., Results: Retrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of €431 527 direct and €2 388 810 indirect costs could have been saved each year., Conclusion: Using QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally €3.81 (95% confidence interval, €3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: This study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account., Methods: An age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually., Results: At an assumed coverage of 50%, adding pediatric vaccination for 2- to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2- to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and €1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2- to 6-year-olds or 2- to 12-year-olds or strategies with trivalent inactivated vaccine., Conclusion: Modeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: In Germany, routine influenza vaccination with quadrivalent influenza vaccines (QIV) is recommended and reimbursed for individuals ≥60 years of age and individuals with underlying chronic conditions. The present study examines the cost-effectiveness of a possible extension of the recommendation to include strategies of childhood vaccination against seasonal influenza using QIV., Methods: A dynamic transmission model was used to examine the epidemiological impact of different childhood vaccination strategies. The outputs were used in a health economic decision tree to calculate the costs per quality-adjusted life year (QALY) gained from a societal and a third-party payer (TPP) perspective. Strain-specific epidemiology, vaccine uptake, and vaccine efficacy data from the 10 non-pandemic seasons from 2003/2004 to 2013/2014 were used, and cost data were drawn mainly from a health insurance claims data analysis and supplemented by estimates from literature. Uncertainty is explored via scenario, deterministic, and probabilistic sensitivity analyses., Results: Vaccinating 2- to 9-year-olds with QIV assuming a vaccine uptake of 40% is cost-saving with a benefit-cost ratio of 1.66 from a societal perspective and an incremental cost-effectiveness ratio of €998/QALY from a TPP perspective. Lower and higher vaccine uptakes show marginal effects, while extending the target group to 2- to 17-year-olds further increases the health benefits while still being below the willingness-to-pay (WTP) threshold. Assuming no vaccine-induced herd protection has a negative effect on the cost-effectiveness ratio, but childhood vaccination remains cost-effective., Conclusion: Routine childhood vaccination against seasonal influenza in Germany is most likely to be cost-saving from a societal perspective and highly cost-effective from a TPP perspective., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Every year in the United States, influenza-related infection causes thousands of deaths, the complications of which require millions of dollars in hospital-related care. The influenza vaccine is proven to effectively reduce incidence of infection and complications from influenza viruses., Local Problem: A clinic in southeast Florida for the uninsured offered influenza immunization at no cost to its patients, yet the immunization rate was still low., Methods: A quality improvement project was conducted to determine whether the use of evidenced-based bundled interventions would increase the rate of the influenza vaccination at the clinic., Interventions: The bundled interventions included mass communication, leadership, improved work flow, and improved access., Results: Evidence-based interventions led to a 597% increase in the influenza uptake rate. Trends were analyzed by using data gathered from the electronic medical record regarding patient demographics, influenza immunization uptake rate, type of visit for the immunizations, and reason for declining. Overcoming the access barrier led to great improvements in this clinic. Initially more vaccines were given in nurse visits; as the season progressed, more vaccines were given by providers in the clinic. Common reasons for patient refusal of the vaccine were fear of side effects and fear of contracting the influenza virus. Streamlined documentation could promote continued staff compliance over time., Conclusions: To reduce influenza-related costs and improve health outcomes, it is imperative that nurse practitioners use evidence-based interventions in the practice setting to increase influenza uptake rates in the adult uninsured population.

For infectious disease prevention, policy-makers are typically required to base policy decisions in light of operational and monetary restrictions, prohibiting implementation of all candidate interventions. To inform the evidence-base underpinning policy decision making, mathematical and health economic modelling can be a valuable constituent. Applied to England, this study aims to identify the optimal target age groups when extending a seasonal influenza vaccination programme of at-risk individuals to those individuals at low risk of developing complications following infection. To perform this analysis, we utilise an age- and strain-structured transmission model that includes immunity propagation mechanisms which link prior season epidemiological outcomes to immunity at the beginning of the following season. Making use of surveillance data from the past decade in conjunction with our dynamic model, we simulate transmission dynamics of seasonal influenza in England from 2012 to 2018. We infer that modified susceptibility due to natural infection in the previous influenza season is the only immunity propagation mechanism to deliver a non-negligible impact on the transmission dynamics. Further, we discerned case ascertainment to be higher for young infants compared to adults under 65 years old, and uncovered a decrease in case ascertainment as age increased from 65 to 85 years of age. Our health economic appraisal sweeps vaccination age space to determine threshold vaccine dose prices achieving cost-effectiveness under differing paired strategies. In particular, we model offering vaccination to all those low-risk individuals younger than a given age (but no younger than two years old) and all low-risk individuals older than a given age, while maintaining vaccination of at-risk individuals of any age. All posited strategies were deemed cost-effective. In general, the addition of low-risk vaccination programmes whose coverage encompassed children and young adults (aged 20 and below) were highly cost-effective. The inclusion of elder age-groups to the low-risk programme typically lessened the cost-effectiveness. Notably, elderly-centric programmes vaccinating from 65-75 years and above had the least permitted expense per vaccine., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Although not directly related to this study, Simon de Lusignan has received funding through his University for membership of advisory boards for Sanofi and Sequirus, and funding for influenza vaccine studies from GSK and Seqirus. All other authors declare that they have no competing interests.

Objective: To determine the costs and reimbursement associated with running a vaccine program in 5 obstetrics/gynecology practices in Colorado that had participated in a 3-year randomized, controlled trial focused on increasing vaccination in this setting., Materials and Methods: This was a secondary analysis on costs from 5 clinics participating in a cluster-randomized controlled trial that assessed the effectiveness of a multimodal intervention to improve vaccination rates in outpatient obstetrics/gynecology clinics in central Colorado. The intervention included designation of an immunization champion within the practice, purchasing recommended vaccines for the practice, guidance on storage and management, implementing practices for routine identification of eligible patients for vaccination using the medical record, implementation of standing orders for vaccination, and vaccine administration to patients. Data on costs were gathered from office invoices, claims data, surveys and in-person observations during the course of the trial. These data incorporated supply and personnel costs for administering vaccines to individual patients that were derived from a combination of time-motion studies of staff and provider clinical activity, and practice reports, as well as costs related to maintaining the vaccination program at the practice level, which were derived from practice reports and invoices. Cost data for personnel time during visits in which vaccination was assessed and/or discussed, but no vaccine was given to the patient were also included in the main analysis. Data on practice revenue were derived from practice reimbursement records. All costs were described in 2014 dollars. The primary analysis was the proportion of costs for the program that were reimbursed, aggregated over all years of the study and combining all vaccines and practices, separated by obstetrics vs gynecology patients., Results: Collectively the 5 clinics served >40,000 patient during the study period and served a population that was 16% Medicaid. Over the 3-year observation period, there were 6573 vaccination claims made collectively by the practices (4657 for obstetric patients, 1916 for gynecology patients). The most expensive component of the program was the material costs of the vaccines themselves, which ranged from a low of $9.67 for influenza vaccines, to a high of $141.40 for human papillomavirus vaccine. Staff costs for assessing and delivering vaccines during patient visits were minimal ($0.09-$1.24 per patient visit depending on the practice and whether an obstetrics or gynecology visit was being assessed) compared with staff costs for maintaining the program at a practice level (ie, assessing inventory, ordering and stocking vaccines; $0.89-$105.89 per vaccine dose given). When assessing all costs compared with all reimbursement, we found that vaccines for obstetrics patients were reimbursed at 159% of the costs over the study period, and for gynecology patients at 97% of the costs. Overall, the vaccination program was financially favorable across the practices, averaging 125% reimbursement of costs across the three study years., Conclusion: Providing routine vaccines to patients in the ambulatory obstetrics/gynecology setting is generally not financially prohibitive for practices, and may even be financially beneficial, though there is variability between practices that can affect the overall reimbursement margin., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Influenza epidemics significantly weight on the Brazilian healthcare system and its society. Public health authorities have progressively expanded recommendations for vaccination against influenza, particularly to the pediatric population. However, the potential mismatch between the trivalent influenza vaccine (TIV) strains and those circulating during the season remains an issue. Quadrivalent vaccines improves vaccines effectiveness by preventing any potential mismatch on influenza B lineages., Methods: We evaluate the public health and economic benefits of the switch from TIV to QIV for the pediatric influenza recommendation (6mo-5yo) by using a dynamic epidemiological model able to consider the indirect impact of vaccination. Results of the epidemiological model are then imputed in a health-economic model adapted to the Brazilian context. We perform deterministic and probabilistic sensitivity analysis to account for both epidemiological and economical sources of uncertainty., Results: Our results show that switching from TIV to QIV in the Brazilian pediatric population would prevent 406,600 symptomatic cases, 11,300 hospitalizations and almost 400 deaths by influenza season. This strategy would save 3400 life-years yearly for an incremental direct cost of R$169 million per year, down to R$86 million from a societal perspective. Incremental cost-effectiveness ratios for the switch would be R$49,700 per life-year saved and R$26,800 per quality-adjusted life-year gained from a public payer perspective, and even more cost-effective from a societal perspective. Our results are qualitatively similar in our sensitivity analysis., Conclusions: Our analysis shows that switching from TIV to QIV to protect children aged 6mo to 5yo in the Brazilian influenza epidemiological context could have a strong public health impact and represent a cost-effective strategy from a public payer perspective, and a highly cost-effective one from a societal perspective.

Background: The protection that an influenza vaccine offers can vary significantly from person to person due to differences in immune systems, body types, and other factors. The question, then, is what is the value of efforts to reduce this variability such as making vaccines more personalized and tailored to individuals., Methods: We developed a compartment model of the United States to simulate different influenza seasons and the impact of reducing the variability in responses to the influenza vaccine across the population., Results: Going from a vaccine that varied in efficacy (0-30%) to one that had a uniform 30% efficacy for everyone averted 16.0-31.2 million cases, $1.9-$3.6 billion in direct medical costs, and $16.1-$42.7 billion in productivity losses. Going from 0-50% in efficacy to just 50% for everyone averted 27.7-38.6 million cases, $3.3-$4.6 billion in direct medical costs, and $28.8-$57.4 billion in productivity losses. Going from 0-70% to 70% averted 33.6-54.1 million cases, $4.0-$6.5 billion in direct medical costs, and $44.8-$64.7 billion in productivity losses., Conclusions: This study quantifies for policy makers, funders, and vaccine developers and manufacturers the potential impact of efforts to reduce variability in the protection that influenza vaccines offer (eg, developing vaccines that are more personalized to different individual factors)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya., Methods: We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872)., Results: The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit., Conclusion: Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.

Background: Influenza is an infectious disease causing a high annual economic and public health burden. The most efficient management of the disease is through prevention with vaccination. Many influenza vaccines are available, with varying efficacy and cost, targeting different age groups. Therefore, strategic decision-making about which vaccine to deliver to whom is warranted to improve efficiency., Objective: We present the use of a constrained optimization (CO) model to evaluate targeted strategies for providing influenza vaccines in three adult age groups in the USA., Methods: CO was considered for identifying an influenza vaccine provision strategy that maximizes the benefits at constrained annual budgets, by prioritizing vaccines based on return on investment. The approach optimizes a set of predefined outcome measures over several years resulting from an increasing investment using the best combination of influenza vaccines., Results: Results indicate the importance of understanding the relative differences in benefits for each vaccine type within and across age groups. Scenario and threshold analyses demonstrate the impact of changing budget distribution over time, price setting per vaccine type, and selection of outcome measure to optimize., Conclusion: Significant gains in cost efficiency can be realized for a decision maker using a CO model, especially for a disease like influenza with many vaccine options. Testing the model under different scenarios offers powerful insights into maximum achievable benefit overall and per age group within the predefined constraints of a vaccine budget.

Purpose: Quadrivalent influenza vaccine (QIV) includes the same strains as trivalent influenza vaccine (TIV) plus an additional B strain of the other B lineage. The aim of the study was to analyse the public health and economic impact of replacing TIV with QIV in different scenarios in Spain., Methods: A dynamic transmission model was developed to estimate the number of influenza B cases prevented under TIV and QIV strategies (<65 years (high risk) and ≥65 years). This model considers cross-protective immunity induced by different lineages of influenza B. The output of the transmission model was used as input for a decision tree model that estimated the economic impact of switching TIV to QIV. The models were populated with Spanish data whenever possible. Deterministic univariate and probabilistic multivariate sensitivity analyses were performed., Results: Replacing TIV with QIV in all eligible patients with current vaccine coverage in Spain may have prevented 138,707 influenza B cases per season and, therefore avoided 10,748 outpatient visits, 3,179 hospitalizations and 192 deaths. The replacement could save €532,768 in outpatient visit costs, €13 million in hospitalization costs, and €3 million in costs of influenza-related deaths per year. An additional €5 million costs associated with productivity loss could be saved per year, from the societal perspective. The budget impact from societal perspective would be €6.5 million, and the incremental cost-effectiveness ratio (ICER) €1,527 per quality-adjusted life year (QALY). Sensitivity analyses showed robust results. In additional scenarios, QIV also showed an impact at public health level reducing influenza B related cases, outpatient visits, hospitalizations and deaths., Conclusions: Our results show public health and economic benefits for influenza prevention with QIV. It would be an efficient intervention for the Spanish National Health Service with major health benefits especially in the population ≥65-year., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: PC has received scientific consultancy from Sanofi Pasteur. ER has received funding for scientific consultancy and speaker fees, as well as congress attendance grants from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme and Pfizer. JD has received funding for scientific consultancy and speaker fees from Sanofi Pasteur and Seqirus. RO has received funding for scientific consultancy and speaker fees from Sanofi Pasteur, GlaxoSmithKline and Seqirus. FM and his institution have received funding for consultancy and research and speaker fees from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme, Pfizer, Astrazeneca, Janssen, Seqirus and Ablynx. AG has received funding for scientific consultancy and speaker fees from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme y Pfizer. JLLB, FPA and HB are employed by the commercial Sanofi Pasteur. MS is employed by the commercial IQVIA and works in consultancy projects with Sanofi Pasteur and other Pharmaceutical Companies. JLLB, FPA, HB and MS were involved in the design of the study, data collection and the decision to publish the results. The manuscript was reviewed by the study sponsor prior to submission. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Background: Seasonal influenza is a highly contagious infection that might lead to serious clinical complications and incurs a conspicuous socio-economic impact. Influenza vaccination is currently recommended only for specific groups of healthy adults (such as healthcare workers) even though it was demonstrated to be effective in reducing absenteeism and decreased workers' productivity during flu epidemic period. The main purpose of this study is to analyse the extent of absences due to illness following a voluntary flu immunization program among the Komatsu Italia Manufacturing company's personnel during the flu season 2017-2018. Secondly, we aimed at performing a cost-benefit analysis of the vaccination campaign from the company's perspective., Study Design: This is an observational cohort study conducted during the period between the 14th week of 2017 and the 13th week of 2018 (from 03/04/2017 to 01/04/2018). The study population was the personnel of Komatsu Italia Manufacturing S.p.A. on duty during the study period., Methods: For each subject the following data were collected: sex, date of birth, professional profile, seasonal influenza immunization status and sick-leave days. Sick-leave days were compared among the influenza epidemic period and the previous one between vaccinated and unvaccinated and any difference in days of absence was considered to be caused by seasonal influenza., Results: Out of 408 employees, 60 (14.7%) accepted the voluntary influenza vaccination. In multivariate analysis (logistic model) an age ≥ 50 years was the only predictor for vaccination acceptance (ORM 3.11 p<0.001). During the flu period, the monthly mean of sick-leave days per employee was significantly lower among the vaccinated than the unvaccinated, respectively of 0.328 days/person vs 0.752 days/person (p = 0.022). Unvaccinated employees reported a higher average of sick-leave days during the flu period compared to the previous non-influenza period (0.752 days/month/person vs 0.337 days/month/person p <0.001). The monthly mean cost for sickness absences per employee was significantly higher for an unvaccinated subject compared to one vaccinated, respectively € 129.00 and € 54.00 (p = 0.028). The overall net saving estimated was € 314.00 per person vaccinated., Conclusions: Influenza vaccination proved to be an extraordinary preventive tool and a cost-effective intervention. However, influenza immunization seems to be unappealing among healthy adults and higher flu vaccination coverages could be achieved through educational interventions possibly addressing young employees who showed little interest in vaccination. Finally, among health promotion interventions, companies should point out the importance of flu vaccination both for the individual wellbeing and the company environment.

Introduction: Influenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy., Methods: A decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature., Results: Switching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74-7721.67., Conclusion: Introducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [HR and CM are permanent employees of the Seqirus group of companies. All other authors have no potential conflicts of interest to declare]., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In many countries, annual immunization with inactivated influenza vaccine (IIV) is recommended for children with medical risk conditions. Prior cost-effectiveness analyses found such immunization to be cost saving, but assumed effectiveness against non-severe influenza outcomes and a higher effectiveness against severe influenza outcomes than recent studies would suggest. However, recent vaccine studies do not indicate any reduction in community or outpatient disease episodes in IIV immunized individuals. We therefore evaluated cost-effectiveness of IIV immunization in children with medical risk conditions in the Netherlands, assuming that IIV reduces influenza-related hospitalization and death, but has no meaningful impact on non-severe health outcomes., Methods: A health economic decision tree model was developed to evaluate health effects and costs of annual IIV immunization versus no immunization. Model inputs were based on our study on influenza-related primary care visits and other literature. Immunization was considered cost effective if associated costs were less than €20,000 per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analyses were performed to assess robustness of results, and one-way sensitivity analyses and scenario analyses were done to assess the influence of individual parameters., Results: Annual IIV prevents an average of 1.59 influenza-related hospitalizations and 0.02 deaths per 1,000 children with medical risk conditions. This results in an expected QALY gain of 0.43 at incremental costs of €21,564 per 1,000 children, corresponding to an incremental cost-effectiveness ratio (ICER) of €50,297/QALY compared to no immunization. Under base case assumptions, immunization had a 5% probability of being cost effective. Results were most influenced by vaccine efficacy against fatal influenza, QALY loss due to death, and mortality rate., Conclusions: If IIV only reduces severe disease outcomes, as current evidence suggests, annual immunization of medical risk children is unlikely to be cost effective. Results should however be interpreted with caution as cost-effectiveness is largely dependent on incidence and QALY losses for fatal influenza, for which evidence is scarce., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)