Following the development of a value of vaccination (VoV) framework for health technology assessment/cost-effectiveness analysis (HTA/CEA), and identification of three vaccination benefits for near-term inclusion in HTA/CEA, this final paper provides decision makers with methods and examples to consider benefits of health systems strengthening (HSS), equity, and macroeconomic gains. Expert working groups, targeted literature reviews, and case studies were used. Opportunity cost methods were applied for HSS benefits of rotavirus vaccination. Vaccination, with HSS benefits included, reduced the incremental cost-effectiveness ratio (ICER) by 1.4–50.5% (to GBP 11,552–GBP 23,016) depending on alternative conditions considered. Distributional CEA was applied for health equity benefits of meningococcal vaccination. Nearly 80% of prevented cases were among the three most deprived groups. Vaccination, with equity benefits included, reduced the ICER by 22–56% (to GBP 7014–GBP 12,460), depending on equity parameters. Macroeconomic models may inform HTA deliberative processes (e.g., disease impact on the labour force and the wider economy), or macroeconomic outcomes may be assessed for individuals in CEAs (e.g., impact on non-health consumption, leisure time, and income). These case studies show how to assess broader vaccination benefits in current HTA/CEA, providing decision makers with more accurate and complete VoV assessments. More work is needed to refine inputs and methods, especially for macroeconomic gains.

Introduction In the post-pandemic era, people with underlying medical conditions continue to be at increased risk for severe COVID-19 disease, yet COVID-19 vaccination uptake remains low. This study estimated the clinical and economic impact of updated 2023/24 Moderna COVID-19 vaccination among high-risk adults versus no 2023/24 vaccination and versus updated Pfizer/BioNTech vaccination. Methods A static Markov model was adapted for high-risk adults, including immunocompromised (IC), chronic lung disease (CLD), chronic kidney disease (CKD), cardiovascular disease (CVD), and diabetes mellitus (DM) populations in the United States (US). Results Vaccination with the updated Moderna vaccine at current coverage rates was estimated to prevent considerable COVID-19 hospitalizations in CLD (101,309), DM (97,358), CVD (47,830), IC (14,834), and CKD (13,558) populations versus no 2023/24 vaccination. Vaccination also provided net medical cost-savings of US$399 million (M)–2129M (healthcare payer) and $457M–2531M (societal perspective), depending on population. The return-on-investment was positive across all conditions ($1.10–$2.60 gain for every $1 invested). Healthcare savings increased with a relative 10% increase in current vaccination coverage ($439M–$2342M), and from meeting US 2030 targets of 70% coverage ($1096M–$5707M). Based on higher vaccine effectiveness observed in real-world evidence studies, updated Moderna vaccination was estimated to prevent additional COVID-19 hospitalizations in DM (13,105), CLD (10,359), CVD (6241), IC (1979), and CKD (942) versus Pfizer/BioNTech’s updated vaccine, with healthcare payer and societal cost-savings, making it the dominant strategy. Healthcare savings per patient vaccinated with Moderna versus Pfizer/BioNTech’s updated vaccine were $31.00–$59.00, depending on population. Results were robust across sensitivity/scenario analyses. Conclusions Updated 2023/24 Moderna COVID-19 vaccination was estimated to provide significant health benefits through prevention of COVID-19 in high-risk populations, and cost-savings to healthcare payers and society, versus no 2023/24 vaccination and updated Pfizer/BioNTech vaccination. Increasing current low COVID-19 vaccination coverage rates was estimated to be cost-saving while preventing many more severe infections and hospitalizations in these high-risk populations. A graphical abstract is available with this article. Graphical Abstract

Introduction: In the post-pandemic era, people with underlying medical conditions continue to be at increased risk for severe COVID-19 disease, yet COVID-19 vaccination uptake remains low. This study estimated the clinical and economic impact of updated 2023/24 Moderna COVID-19 vaccination among high-risk adults versus no updated vaccination and versus updated Pfizer/BioNTech vaccination. Methods: A static Markov model was adapted for high-risk adults, including immunocompromised (IC), chronic lung disease (CLD), chronic kidney disease (CKD), cardiovascular disease (CVD), and diabetes mellitus (DM) populations in the United States. Results: Vaccination with the updated Moderna vaccine at current coverage rates was estimated to prevent considerable COVID-19 hospitalizations in CLD (101,309), DM (97,358), CVD (47,830), IC (14,834) and CKD (13,558) populations versus no updated vaccination. Vaccination also provided net medical cost savings of $399M–2,129M (healthcare payer) and $457M–2,531M (societal perspective), depending on population. The return-on-investment was positive across all conditions ($1.10–$2.60 gain for every $1 invested). Healthcare savings increased with a relative 10% increase in current vaccination coverage ($439M–$2,342M), and from meeting US 2030 targets of 70% coverage ($1,096M–$5,707M). Based on higher vaccine effectiveness observed in real-world evidence studies, updated Moderna vaccination was estimated to prevent additional COVID-19 hospitalizations in DM (13,105), CLD (10,359), CVD (6,241), IC (1,979), and CKD (942) versus Pfizer/BioNTech’s updated vaccine, with healthcare payer and societal cost savings, making it the dominant strategy. Healthcare savings per patient vaccinated with Moderna versus Pfizer/BioNTech’s updated vaccine were $31-59, depending on population. Results were robust across sensitivity/scenario analyses. Conclusions: Updated 2023/24 Moderna COVID-19 vaccination was estimated to provide significant health benefits through prevention of COVID-19 in high-risk populations, and cost-savings to healthcare payers and society, versus no vaccination and updated Pfizer/BioNTech vaccination. Increasing current low COVID-19 vaccination coverage rates was estimated to be cost-saving while preventing many more severe infections and hospitalizations in these high-risk populations. Key Summary Points: Why carry out this study?: In the US, people with underlying medical conditions continue to be at high risk of severe COVID-19, yet vaccination rates are low. The CDC recommends an updated 2024/25 COVID-19 vaccination for everyone aged >6 months. The objective of this study was to estimate the clinical benefits and cost-effectiveness of updated 2023/24 Moderna COVID-19 vaccination in people with high-risk conditions, versus no updated vaccination, and versus updated Pfizer/BioNTech COVID-19 vaccination. What was learned from the study?: COVID-19 vaccination with the updated Moderna mRNA vaccine of people with underlying medical conditions at high-risk of severe COVID-19 was cost-saving versus no updated vaccination. It also provided more health gains with cost savings versus Pfizer/BioNTech, making it the dominant strategy. For every $1 spent on vaccination, the updated Moderna vaccination provided a return-on-investment of $1.10–$2.60 versus no updated vaccination, depending on the high-risk population. Healthcare cost savings were $31-59 per patient vaccinated with Moderna’s versus Pfizer/BioNTech’s updated vaccination, depending on the high-risk population. A relative 10% increase in vaccination coverage rates prevented 10% more hospitalizations and deaths, and increased healthcare and societal cost savings in all high-risk populations, with the potential for significant health and financial benefits with greater vaccine coverage rates.

Introduction Influenza is a highly transmissible respiratory viral infection, with a risk of severe complications and excess respiratory mortality. Clinical trial data showed that baloxavir was more effective than oseltamivir for reducing duration of virus shedding, which is a key predictor of transmission. Consideration of the effect of treatments on transmission rates is important to ensure that the value of treatments is captured. This study assessed the cost-effectiveness of different treatment strategies with baloxavir and oseltamivir, considering their impact on influenza transmission. Methods The analysis used two models: a dynamic transmission model to estimate influenza incidence, with outputs incorporated in a static population-level decision tree model, in order to evaluate the clinical outcomes and cost-effectiveness of treatment strategies with different shares of baloxavir and oseltamivir from the healthcare payer’s perspective in Japan. Clinical data were sourced from phase 3 trials, and cost inputs were informed by the Ministry of Health, Labour and Welfare, as well as JammNet. Sensitivity and scenario analyses were also conducted. Results Increasing the use of baloxavir in adults from 40% to 50% reduces the number of influenza cases by 17%, hospitalizations by 18%, and deaths by 23%, with cost savings of JPY (Japanese yen) 16,280 million and 10,486 quality-adjusted life years (QALYs) gained, in the total population in Japan. Across all risk and age subgroups, increasing the share of baloxavir was cost-saving and more effective, and, therefore, was considered dominant, which was also confirmed by the sensitivity analysis. Conclusion Treatment of influenza with baloxavir is anticipated to offer value for money within Japan’s healthcare system, delivering significant clinical benefits both for the general population and for all age and risk groups. Accounting for the treatment’s impact on influenza transmission adds another dimension of value and further reinforces the evidence supporting the growing use of baloxavir in Japan.

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease in older adults. Despite growing recognition of RSV as a public health concern, vaccination options remain limited. This study assessed the potential long-term public health impact of extended mRNA-1345 RSV vaccination campaigns. Methods: A dynamic transmission model, stratified by age, was developed to evaluate the epidemiological and clinical impact of RSV vaccination in the UK over a 20-year time horizon. Eight vaccination strategies were assessed: two reflecting the JCVI recommendation for the 2024–2025 season and its recent extension, and six extended strategies considering broader eligible age groups, higher coverage, and/or revaccination every 2 or 3 years. Two exploratory analyses and extensive model validation versus reported data were also conducted. Results: Strategies combining broader age eligibility (≥60 years), higher coverage (80%), and 2-year revaccination achieved the greatest impact, preventing 310,000 hospitalisations over 20 years in the total UK population. Exploratory analyses showed that the expected public health impact might exceed the estimates presented in this analysis, if an alternative vaccine efficacy profile or the projected demographic shift would be confirmed. Conclusions: Extended RSV vaccination strategies including broader age eligibility and routine revaccination could offer substantial public health benefits in the UK. Targeting adults aged ≥60 years is expected to be particularly efficient in achieving a sustainable reduction in RSV burden. These findings could provide valuable support for national policy discussions on optimising RSV vaccination strategies in older adults, particularly regarding target age groups, revaccination schedules, and long-term programme planning.

Introduction Respiratory syncytial virus (RSV) is an important cause of respiratory disease in older adults and adults with chronic medical conditions, contributing substantially to the healthcare burden in Italy. The availability of effective RSV vaccines provides an opportunity to reduce RSV-related morbidity, mortality, and healthcare costs in populations at high risk of severe disease. This study evaluates the potential public health impact and cost-effectiveness of vaccination using mRNA-1345 administered as a single dose compared with no vaccination in Italian high-risk adults aged 60-74 years and all adults aged ≥75 years. Methods A static decision-analytic model was developed to project clinical and economic outcomes over a 5-year time horizon. Economic outcomes were evaluated from the Italian National Health Service (Servizio Sanitario Nazionale, SSN) perspective. Model inputs were informed by the most recent Italian epidemiological, clinical, and economic evidence, supplemented by published international data when necessary. Deterministic, probabilistic, and scenario analyses were conducted to assess the impact of uncertainty in model inputs and assumptions on the study results. Results Vaccination with mRNA-1345 in high-risk adults aged 60-74 years and all adults aged ≥75 years was projected to avert over 19,800 hospitalizations, 4,000 emergency department visits, 381,000 outpatient visits, 6,000 RSV-attributable deaths, and 212,000 antibiotic prescriptions compared with no vaccination over a 5-year period. The total incremental cost of €1,143 million and the additional 47,477 QALYs gained resulted in an ICER of €24,078, which was below the commonly referenced willingness to-pay range of €33,000-40,000 per QALY gained. Sensitivity analyses confirmed robustness of the analysis results. Conclusions Vaccination with mRNA-1345 is a cost-effective strategy for the prevention of RSV in high-risk adults aged 60-74 years and all adults ≥75 years in Italy and has the potential to provide substantial public health benefits.