Journal of Medical Economics

ObjectiveThe main objective was to estimate the potential public health impact and cost-effectiveness of an annual dose of mRNA-1273 (2025/2026 formula) in the United States (US) for the 2025-2026 season compared with no vaccination in the mRNA-1273 licensed population (6 months-64 years with underlying medical conditions and all [&ge;]65 years). mRNA-1273 was also compared to BNT162b2 in high-risk adults ages 18-64 years and all [&ge;]65 years. MethodsAnalyses were conducted using a previously developed static decision-analytic model (1-year horizon) from the societal cost perspective. Vaccine effectiveness (VE) against infection and hospitalization for mRNA-1273 versus no vaccination was based on a 2024-2025 real world effectiveness study. VE estimates for mRNA-1273 versus BNT162b2 were based on systematic literature reviews and meta-analyses. Cost-effectiveness was assessed in terms of incremental cost per quality-adjusted life-year (QALY) gained and the benefit cost ratio (BCR) in the licensed target population as well as age-specific subgroups. Sensitivity and scenario analyses were performed. ResultsThe incremental cost per QALY gained for mRNA-1273 compared to no vaccine was $23,265. For every 1 USD of mRNA-1273 vaccine related costs, there is a return of 1.91-7.90 dollars in societal perspective cost savings and monetized health benefit gained. In the subgroup of high-risk individuals 6 months-4 years, mRNA-1273 was associated with lower costs and improved health outcomes, resulting in mRNA-1273 dominating no vaccine. Study results are sensitive to COVID-19 incidence, percentage hospitalized, post-discharge mortality, and VE assumptions. Compared to BNT162b2, given improved clinical outcomes, combined with a lower vaccine unit cost, mRNA-1273 was shown to dominate BNT162b2. ConclusionsmRNA-1273, the only licensed vaccine for those <5 years of age at high risk of severe COVID-19 related outcomes, could substantially reduce the clinical and economic burden of COVID-19 among US high-risk populations and older adults. These benefits were observed both in comparison to no vaccination and the BNT162b2 vaccine.

AimsCOVID-19 disease burden in United States (US) adults [&ge;]65 years and persons with underlying medical conditions remains high. This modeling study estimates the cost-effectiveness of the next-generation COVID-19 mRNA-1283 vaccine in those ages 12-64 at high-risk of severe COVID-19 outcomes and all adults [&ge;]65 years. MethodsmRNA-1283 was compared to no annual vaccination and originally licensed mRNA vaccines mRNA-1273 and BNT162b2. Analyses were conducted using a static decision-analytic model (1-year horizon). Vaccine effectiveness (VE) against infection and hospitalization for mRNA-1283 versus no vaccination was based on relative VE (rVE) from the Phase 3 pivotal randomized controlled trial comparing mRNA-1283 against mRNA-1273 and mRNA-1273 real-world data. rVE estimates for mRNA-1283 versus BNT162b2 were based on an indirect treatment comparison. The societal incremental cost per quality-adjusted life-year (QALY) gained and the benefit cost ratio (BCR) were calculated. ResultsDuring the 2025/2026 season, a single dose of mRNA-1283 was estimated to yield an incremental cost per QALY gained of $16,241 compared to no vaccine. The BCR for the base case strategy ranged from 2.16-9.74 USD returned for one dollar spent for mRNA-1283. mRNA-1283 was shown to dominate originally licensed COVID-19 vaccines in analyses of the target population. Results are sensitive to COVID-19 incidence, hospitalization rates, post-discharge mortality rates, and VE. LimitationsThe real-world effectiveness and safety of mRNA-1283 have not yet been established and relative VE estimates should be validated with real-world data. 2025/2026 COVID-19 incidence and vaccine uptake in the US is uncertain. ConclusionsStudy results suggest mRNA-1283 represents a highly cost-effective strategy (considering a $100,000-150,000 per QALY willingness-to-pay threshold) to reduce burden of COVID-19 among the target population. Given the finding of mRNA-1283 dominance in this population compared to originally approved mRNA vaccines, mRNA-1283 provides a valuable option to optimize US COVID-19 immunization programs and protect those most vulnerable.

AimsCOVID-19 disease burden in United States (US) older adults [&ge;]65 years and persons with underlying medical conditions remains high. This modeling study provides an interim estimate of the anticipated public health impact of the next-generation COVID-19 mRNA-1283 vaccine in these populations at high-risk of severe COVID-19 outcomes. MethodsmRNA-1283 was compared to no vaccination and originally licensed mRNA COVID-19 vaccines mRNA-1273 and BNT162b2. Analyses were conducted using a static decision-analytic model (1-year horizon). Vaccine effectiveness (VE) against infection and hospitalization for mRNA-1283 versus no vaccination was based on the relative VE (rVE) from the Phase 3 pivotal randomized controlled trial comparing mRNA-1283 against mRNA-1273 and mRNA-1273 real-world data. rVE estimates for mRNA-1283 versus BNT162b2 were based on an indirect treatment comparison. Clinical outcomes calculated included total numbers of symptomatic infections, outpatient and long COVID cases, hospitalizations, and deaths. Sensitivity and scenario analyses were performed. ResultsDuring the 2024/2025 season in the US, a single dose of the mRNA-1283 vaccine was estimated to prevent approximately 2.9 (1.3-4.3) million symptomatic infections, 171,000 (77,000-260,000) hospitalizations, and 22,350 (10,050-33,480) deaths compared to no vaccination. Compared to BNT162b2, mRNA-1283 was estimated to avert an additional 0.79 million symptomatic infections, 58,000 hospitalizations, and 7,565 deaths. Compared to mRNA-1273, mRNA-1283 was estimated to avert an additional 0.56 million symptomatic infections, 46,000 hospitalizations, and 5,920 deaths. Across all scenarios the majority of severe COVID-19 cases (i.e., hospitalizations and deaths) were prevented among older adults [&ge;]65 years. LimitationsThe real-world effectiveness and safety of mRNA-1283 have not yet been established and the relative VE estimates should be validated with real-world data. Future COVID-19 incidence and incidence pattern throughout the season is uncertain. ConclusionsInterim results suggest that the next-generation COVID-19 mRNA-1283 vaccine could substantially reduce the clinical burden of COVID-19 among those at high risk of severe disease. Compared to no vaccination and originally approved mRNA vaccines, mRNA-1283 provides a valuable option to potentially enhance COVID-19 immunization programmes and protection of those most vulnerable.

Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically-attended COVID-19 with 2 doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically-attended COVID-19 among IC adults in the US. The HealthVerity (HV) medical and pharmacy claims database, which contains data from >330 million patients, was the data source. Both subgroup and sensitivity analyses were conducted in addition to the core comparisons noted. In propensity score-adjusted analyses, receiving mRNA-1273 vs BNT162b2 as third dose was associated with 32% (relative risk [RR] 0.68; 95% confidence interval [CI] 0.51-0.89), 29% (0.71; 0.57-0.86), and 23% (0.77; 0.62-0.93) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically-attended COVID-19 were 8% (0.92; 0.86-0.98), 6% (0.94; 0.90-0.98), and 2% (0.98; 0.94-1.02), respectively. Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically-attended COVID-19 among IC adults in the US.

Background Immunocompromised (IC) individuals are at increased risk of COVID-19 infection-related severe outcomes. Moderna and Pfizer-BioNTech COVID-19 mRNA vaccines are available in Canada, and differences in vaccine effectiveness (VE) have been found between the two in IC individuals. The objective of this analysis was to compare the clinical and economic impact of a Moderna XBB.1.5 updated COVID-19 mRNA Fall 2023 vaccine to a Pfizer-BioNTech XBB.1.5 updated COVID-19 mRNA Fall 2023 vaccine in Canadian IC individuals aged [&ge;]18 years. MethodsA static decision-analytic model estimated the number of COVID-19 infections, hospitalizations, deaths, and resulting quality-adjusted life years (QALYs) over a one-year time horizon (September 2023-August 2024) in the Canadian IC adult population (n=894,580). Costs associated with COVID-19 infection were estimated from health care and societal perspectives. The predicted VE of the updated Moderna vaccine was based on prior variant versions, which were well-matched to the circulating variant. Pfizer-BioNTech VE was calculated based on a meta-analysis of comparative effectiveness between both vaccines (relative risk for Moderna vaccine: infection=0.85 [95%CI 0.75-0.97], hospitalization=0.88 [95%CI 0.79-0.97]). The model combined VE estimates with COVID-19 incidence and probability of COVID-19 related severe outcomes. Sensitivity analyses tested the impact of uncertainty surrounding incidence, hospitalization and mortality rates, costs, and QALYs. ResultsGiven the expected higher VE against infection and hospitalizations with the Moderna Fall 2023 vaccine, its use is predicted to prevent an additional 2,411 infections (3.6%), 275 hospitalizations (3.7%), and 47 deaths (4.0%) compared to the Pfizer-BioNTech Fall 2023 vaccine, resulting in 330 QALYs gained, and savings of $7.4M in infection treatment costs, and $0.9M in productivity loss costs. Results were most sensitive to variations in VE parameters, specifically the relative risk of infection and hospitalizations between the vaccines, and waning rates. ConclusionsIf the Moderna and Pfizer-BioNTech Fall 2023 vaccines protect against infection and hospitalizations similar to previous vaccines, using the Moderna Fall 2023 vaccine would result in substantial public health benefits in IC individuals, as well as provide health care and societal cost savings.

BackgroundSotrovimab, a recombinant human monoclonal antibody (mAb) against SARS-CoV-2 had US FDA Emergency Use Authorization (EUA) for the treatment of high-risk outpatients with mild- to-moderate COVID-19 from May 26, 2021 to April 5, 2022. The study objective was to evaluate the real-world effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality during the time period when the prevalence of circulating SARS-CoV-2 variants was changing between Delta and Omicron sub-lineages in the US. MethodsA retrospective analysis was conducted on de-identified claims data for 1,530,501 patients diagnosed with COVID-19 (ICD-10: U07.1) from September 1, 2021, to April 30, 2022, in the FAIR Health National Private Insurance Claims (FH NPIC(R)) database. Patients meeting EUA high-risk criteria were identified via pre-specified ICD-10-CM diagnoses in records [&le;]24 months prior to their first COVID-19 diagnosis and divided into two cohorts based on claimed procedural codes: treated with sotrovimab ("sotrovimab") and not treated with a mAb ("no mAb"). All-cause hospitalizations and facility-reported all-cause mortality within 30 days of diagnosis ("30-day hospitalization or mortality") were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality among those treated with sotrovimab compared with those not treated with a mAb. ResultsOf the high-risk COVID-19 patients identified, 15,633 were treated with sotrovimab and 1,514,868 were not treated with a mAb. Compared with the no mAb cohort, the sotrovimab cohort was older and had a higher proportion of patients across the majority of high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8,167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, high-risk COVID-19 patients treated with sotrovimab had a 55% relative risk reduction of 30-day hospitalization or mortality (RR: 0.45, 95% CI: 0.41,0.49) and an 85% relative risk reduction of 30-day mortality (RR: 0.15, 95% CI: 0.08, 0.29) compared with high-risk patients not treated with a mAb. From September 2021 to April 2022, sotrovimab maintained clinical effectiveness with relative risk reductions of 30-day hospitalization or mortality ranging from 46% to 71%. Stratifying by high-risk condition, sotrovimab-treated patients exhibited statistically significant relative risk reductions of 30-day hospitalization or mortality compared with the no mAb cohort across all high-risk conditions (P<0.0001), ranging from 44% among pregnant women to 70% among patients 65 years and older. ConclusionIn this large, US real-world, observational study of high-risk COVID-19 patients with reported diagnosis between September 2021 and April 2022 during the Delta and early Omicron variant waves, treatment with sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and facility-reported mortality compared with no mAb treatment. Sotrovimab clinical effectiveness persisted throughout the months when Delta and early Omicron sub-lineages were the predominant circulating variants in the US, though there was an uncertain RR estimate in April 2022 with wide confidence intervals due to the small sample size. Sotrovimab clinical effectiveness also persisted among all high-risk subgroups assessed.

Background & ObjectivesIn a previous analysis, a decision-analytic model was used to analyze the clinical and economic impact of the differences in effectiveness between the two licensed mRNA COVID-19 booster vaccines, mRNA-1273 and BNT162b2, in 2022 for adults aged 18 years and older in the United States (US). In this analysis, the same model was used to estimate the impact that administering first booster doses with mRNA-1273 could have had on COVID-related hospitalizations and costs over a 6-month period in 10 developed countries (Australia, Canada, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom [UK], and US), considering updated effectiveness data. MethodsThe model was used to estimate number of hospitalizations and related costs using the actual vaccine distribution for the first COVID-19 booster from each country. These estimates were compared to a scenario where 100% of doses for that 6-month period was assumed to be mRNA-1273. The effectiveness of mRNA-1273 compared to BNT162b2 was estimated from real world data from the UK. ResultsThe total number of doses switched to the mRNA-1273 booster would range from 4.3 million in Spain to 39.4 million in Japan. The number of hospitalizations and associated hospitalization costs would be expected to fall in all countries, with the proportional decrease ranging from 1.1% (16,800 fewer) in Germany to 8.8% (25,100 fewer) in Australia. ConclusionsReal-world effectiveness data suggest that a booster dose of the mRNA-1273 vaccine may be more effective compared to other vaccines used for booster doses. Given this difference in effectiveness, results of this analysis demonstrate that switching to 100% mRNA-1273 boosters would have reduced the number of hospitalizations and associated costs in each country during the first 6 months of the omicron period.

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally-licensed COVID-19 vaccines. Its potential public health and economic impact, in adults [&ge;]60 years and high-risk 18-59 years, was modelled versus no vaccination and originally-licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination, and price premiums over existing vaccines, were determined at a willingness-to-pay threshold of {euro}50,000/quality-adjusted life-year (QALY) gained. Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations and 5,300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5,400 hospitalizations, and 1,200 deaths, saving 9,667 QALYs and over {euro}66.5 million in treatment costs. The EJP was {euro}238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1,309 and 1,679 hospitalizations, respectively), and was cost-effective at an incremental EJP of {euro}62 versus mRNA-1273, and {euro}80 versus BNT162b2. The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally-licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

Aims: COVID-19 and influenza continue to impose a substantial burden on the Canadian healthcare system, particularly among adults aged greater than 65 years. This study compared the clinical and economic outcomes of a Stand-alone vaccination strategy with separate influenza and COVID-19 vaccines versus a Combination strategy incorporating mRNA-1083, an investigational vaccine targeting both infections. Methods: The study adopted the public healthcare payer perspective and adapted a previously published static model to predict COVID-19 and influenza infections across a one-year time horizon. Relative vaccine effectiveness (rVE) for mRNA-1083 against COVID-19 compared with the stand-alone vaccine (SPIKEVAX) was based on the pivotal clinical trial of mRNA-1083s COVID-19 component (mRNA-1283). For influenza, no incremental VE was assumed versus the adjuvanted stand-alone vaccine (FLUAD). Infections were modeled independently. Clinical outcomes included symptomatic infections, hospitalizations, and deaths. The economically justifiable price (EJP) was calculated at the willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year (QALY) gained. mRNA-1083 uptake was assumed to yield absolute increases in COVID-19 and influenza coverage by 10% and 3%, respectively. Results: Compared with the Stand-alone strategy, the Combination strategy was projected to reduce the number of COVID-19-related symptomatic infections, hospitalizations, and deaths (n=71,074; 5,008; 935, respectively), and corresponding influenza outcomes (n=3,985; 362; 69, respectively). The use of mRNA-1083 within the Combination strategy generated a cost-savings of $90,440,471 in vaccine administration fees and an EJP of $304 per dose. Results were sensitive to rVE, coverage, administration fees, mortality and incidence. Limitations: mRNA-1083s rVE is being evaluated in clinical trials and the impact of mRNA-1083 on vaccine coverage and administration fees is uncertain. Conclusions: mRNA-1083 may reduce the burden of COVID-19 and influenza in adults aged greater than 65 years in Canada, while offering good economic value because it has the potential to increase coverage and VE while reducing administration fees.

BackgroundWith shifting epidemiology and changes in the vaccine funding landscape, resource use considerations for ongoing COVID-19 vaccination programs are increasingly important. We assessed the cost-effectiveness of COVID-19 vaccination programs, where eligibility is defined by combinations of age and chronic medical conditions, including a strategy similar to current Canadian recommendations, from the health system and societal perspectives. MethodsWe used a static, individual-based probabilistic model simulating medically attended COVID-19 in a population of 1 million people followed over a 15-month time period to estimate costs in 2023 Canadian dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 1.5%. COVID-19 epidemiology, vaccine characteristics, and costs were based on the most recently available data. ResultsAnnual vaccination for adults aged 65 years and older consistently emerged as a cost-effective intervention, with ICERs less than $50,000 per QALY compared to no vaccination for a range of model assumptions. Adding a second dose for adults aged 65 years and older or expanding programs to include vaccination for younger age groups, including those at higher risk of COVID-19 due to chronic medical conditions, generally resulted in ICERs of greater than $50,000 per QALY. Shifting timing of vaccination programs to better align with periods of high COVID-19 case occurrence could result in biannual vaccination for those aged 65 and older being a cost-effective strategy. ConclusionsCOVID-19 vaccination programs may be cost-effective when focused on groups at higher risk of disease. Optimal timing of vaccination could improve the cost-effectiveness of various strategies.

Respiratory syncytial virus (RSV) is a highly infectious virus, and infants and young children are particularly vulnerable to its progression to severe lower respiratory tract illness (LRTI). Nirsevimab, an extended half-life monoclonal antibody, was recently approved in Canada as a passive immunization intervention for the prevention of RSV LRTI. A static decision tree model was utilized to determine the cost-effectiveness of nirsevimab in Canadian infants compared to current standard of care (palivizumab for infants born preterm, and with specific chronic conditions) and generate an optimal price per dose (PPD) at accepted willingness-to-pay (WTP) thresholds. Various health outcomes (including hospitalization, ICU, and mechanical ventilation) and healthcare costs were calculated over one RSV season, with any necessary follow-up prophylaxis in the second season for three infant categories (palivizumab-eligible, preterm, and term). All health-related parameters and costs were tailored to the Canadian environment. Compared to scenarios where only at-risk segments of the infant population received nirsevimab, the base case (administering nirsevimab to all infants in their first RSV season) was the most cost-effective versus standard care: the PPD was $692 at a $40,000/QALY WTP threshold, using average costing data assumptions across all scenarios. Compared to standard care, the base case scenario could avoid 18,249 RSV-related health outcomes (reduction of 9.96%). Variations in discount rate, distribution of monthly RSV infections, nirsevimab coverage rate for infants born at term, and palivizumab cost had the most significant model impact. Passive immunization of all infants with nirsevimab can significantly reduce RSV-related health and economic burden across Canada.

ObjectivesTo assess the clinical and economic impact, and cost-effectiveness, of a 2024 Winter and Summer COVID-19 Vaccination Campaign (2024 Vaccination Campaign) in Australia compared to no 2024 Vaccination Campaign. DesignModelling study using a COVID-19 susceptible-exposed-infect-recovered (SEIR) dynamic transmission model and a COVID-19 vaccination and infections consequences decision analytic model. Setting, Participants: Australia; Winter 2024 COVID-19 vaccination targeting adults aged [&ge;]18 years, with those aged [&ge;] 65 years eligible for an additional Summer 2024 dose. Intervention: 2024 Vaccination Campaign using a Moderna variant-updated mRNA vaccine compared to no 2024 Vaccination Campaign. Main outcome measures: Projected number of symptomatic infections, hospitalisation, deaths, and cases of long COVID prevented; quality-adjusted life-years (QALYs) gained, incremental cost of the 2024 Vaccination Campaign, and incremental cost-effectiveness ratio (ICER) of the campaign compared to No Vaccination Campaign. ResultsCompared to no Vaccination Campaign, a 2024 Vaccination Campaign in Australia is predicted to prevent 241,600 symptomatic infections, 13,500 COVID-19 hospitalisations, 1,200 deaths, and 11,900 cases of long COVID, representing a decrease of 16%, 23%, 26%, and 17%, respectively. This resulted in 19,200 fewer QALYs lost. COVID-19 treatment costs saved with the 2024 Vaccination Campaign was $511.7 million. This partially offset the costs associated with vaccination and adverse event treatment ($1.03 billion), resulting in an incremental 2024 Vaccination Campaign cost of $522 million for a population of 26.3 million, with 4.35 million vaccinations administered. The ICER was $27,100/QALY gained. Increasing the vaccine coverage rate to that observed with influenza vaccination prevented more cases of infection, hospitalisation, and deaths compared to the base case, with an ICER of $34,400/QALY gained. ConclusionEven in the endemic setting with high hybrid immunity, substantial clinical and economic benefits to vaccinating those aged [&ge;]18 years against COVID-19 remain. These benefits may be amplified with increased vaccination coverage. Summary boxThe known: Vaccination campaigns were a cost-effective strategy to battle the clinical and economic impact of COVID-19 during the pandemic. Even in the endemic setting, COVID-19 continues to cause substantial clinical and economic burden to Australia. The new: Even in a population with high hybrid immunity, COVID-19 vaccination campaigns continue to be cost-effective in Australia in the endemic setting. Clinical benefits are increased by improving the vaccination coverage rate, and not narrowing the targeted population. The implications: In Australia, annual COVID-19 vaccination campaigns should continue. Increasing the COVID-19 vaccination coverage rates and including a broader recommended population is feasible with an acceptable incremental cost-effectiveness ratio.

ObjectiveTo assess knowledge and confidence in COVID-19 vaccine counseling among practitioners who provide care to pregnant persons and to describe factors associated with confidence in counseling. Study DesignA web-based anonymous survey was distributed via email to a cross-sectional convenience sample of OB/GYN, Primary Care, and Internal Medicine faculty at three hospitals in a single healthcare network in Massachusetts. Individual demographics and institution-specific variables were included in the survey along with questions assessing both attitudes toward COVID-19 illness in pregnancy as well as confidence in counseling regarding the use of the vaccine for pregnant patients. ResultsAlmost all providers (151, 98.1%) reported already receiving or being scheduled to receive a COVID-19 vaccine, and a majority of providers (111, 72.1%) reported that they believe the benefits of the mRNA COVID-19 vaccine in pregnancy outweigh the risks. Forty-one (26.6%) reported feeling very confident in counseling patients who primarily speak English about the evidence for mRNA vaccination in pregnancy, and 36 (23%) reported feeling very confident in counseling patients who are not primarily English-speaking. Forty-three providers (28.1%) expressed strong confidence in their comfort talking to individuals with vaccine hesitancy based on historic and continued racism and systemic injustices. The sources that survey respondents most commonly used to find information regarding COVID-19 vaccination in pregnancy were the CDC (112, 74.2%), hospital-specific resources (94, 62.3%) and ACOG (82, 54.3%). ConclusionWhile providers reported high personal uptake of COVID-19 vaccination and felt that the benefits of vaccination outweigh the risks in pregnancy, less than one-third felt very confident in counseling pregnant patients about available evidence for mRNA vaccine safety in pregnancy. Ensuring that providers feel comfortable bridging the gap between their belief that the vaccine is beneficial for pregnant patients and their comfort with holding conversations with patients regarding vaccination is paramount in order to ensure equitable access to vaccines for pregnant patients.

BackgroundThe cost-effectiveness of immunisation strategies with a long-acting monoclonal antibody (nirsevimab) and/or a protein-based maternal vaccine (RSVpreF) for protecting infants from Respiratory Syncytial Virus (RSV)-associated illness has not been previously determined for Canada. We estimated the health benefits and cost-effectiveness of nirsevimab for immunising the entire birth cohort regardless of gestational age or other risk factors. Additionally, we evaluated a combined strategy of year-round vaccination of pregnant women with RSVpreF and immunisation of high-risk infants with nirsevimab during RSV season. MethodsWe developed a discrete-event simulation model, parameterized with the data on RSV incidence, outpatient care, hospitalisations, and deaths. Intervention scenarios targeting twelve monthly birth cohorts and pregnant women were evaluated over a time horizon of one year. Taking into account the costs associated with RSV-related outcomes, we calculated the net monetary benefit using the quality-adjusted life-year (QALY) gained. Further, we determined the range of price-per-dose (PPD) for nirsevimab and RSVpreF within which the program was cost-effective. Cost-effectiveness analyses were conducted from both healthcare and societal perspectives. FindingsUsing a willingness-to-pay of CAD$50,000 per QALY gained, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a PPD of up to $290, with an annual budget impact of $83,978 for 1,113 infants per 100,000 population. An alternative, combined strategy of vaccinating pregnant women and immunising only high-risk infants would lead to a lower budget impact of $49,473 per 100,000 population with a PPD of $290 and $195 for nirsevimab and RSVpreF, respectively. This combined strategy would reduce infant mortality by 76% to 85%, comparable to 78% reduction achieved through a nirsevimab-only program for immunising the entire birth cohort. PPD for cost-effective programs with nirsevimab was sensitive to the target population among infants. InterpretationPassive immunisation of infants under 6 months of age with nirsevimab and vaccination of pregnant women with RSVpreF could be a cost-effective strategy for protecting infants during their first RSV season. FundingThis study was supported by the Canadian Immunisation Research Network (CIRN) and the Canadian Institutes of Health Research (CIHR). Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada (MfPH and Discovery grants). Alison P. Galvani acknowledges support from the The Notsew Orm Sands Foundation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevention of RSV disease in infants under 1 year of age has relied on palivizumab, a short-acting monoclonal antibody, administered monthly to high-risk infants during the period in which RSV is circulating in annual epidemics. New preventive measures including nirsevimab (a long-acting monoclonal antibody for immunising infants) and RSVpreF (a protein-based vaccine for immunising pregnant women) have been developed to reduce the risk of severe RSV illness in the first six months of life. However, no prior study has evaluated cost-effectiveness of these interventions in Canada with recently available efficacy estimates from randomised controlled clinical trials. Added value of this studyUsing a discrete-event simulation model, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a price per dose of up to $290. Year-round vaccination of pregnant women with RSVpreF, followed by immunising infants at high-risk of severe RSV disease with nirsevimab as a combined strategy required a lower budget impact compared to the nirsevimab-only program for the entire birth cohort during the RSV season, while averting similar RSV-related infant mortality. Implications of all the available evidencePrevention strategies against RSV disease in infants using nirsevimab and RSVpreF vaccine could be cost-effective. A combined strategy of these interventions could reduce the budget impact to the healthcare system.

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

BackgroundThe Most Favored Nation (MFN) policy is a mechanism that incorporates foreign prices to determine the maximum allowable net price for any branded drug within US government-funded healthcare. Two proposed rules, the Global Benchmark for Efficient Drug Pricing ("GLOBE") (90 Fed. Reg. 60,244) for Medicare Part B and the Guarding US Medicare Against Rising Drug Costs ("GUARD") (90 Fed. Reg. 60,338) for Medicare Part D, invoke the Center for Medicare and Medicaid Innovation Centers payment and service model demonstration and waiver authority, under Section 1115A of the Social Security Act (42 U.S.C. [&#167;] 1315a), to calculate the US MFN price which is the lowest average price within a basket of specified foreign countries. Unlike voluntary manufacturer agreements, GLOBE and GUARD would mandate participation from all applicable manufacturers. MethodsWe derive MFNs potential impact on Medicare pricing from a proprietary dataset provided by IQVIA which contained net prices for the top 37 oncology products by total US sales from January 1, 2019 through June 30, 2025 ranked by total US sales in the following countries: Australia, Belgium, France, Germany, Ireland, Italy, South Africa, Spain, Switzerland, the UK, and the US. For each drug, we select the lowest GDP-adjusted international price from a basket of those countries within 60% of the US GDP per capita, adjusted for purchasing power parity, and calculate the reduction in US price required to match its MFN price, and hence the corresponding reduction in revenues under MFN. A retrospective Net Present Value (NPV) analysis is then used to address the counterfactual question of whether each drug would have been developed had MFN pricing been in place at the time of its FDA approval. ResultsUnder MFN, the average reduction in US prices across our drug cohort was 67%. Eighty-four percent of the 37 cancer drugs in our cohort evidenced a negative NPV if MFN had been in place at the time of their FDA approval and the commercial market is impacted. When the analysis is restricted to MFNs impact on Medicare, the indications for these lost drugs have a total US population of 2.4 million patients. When the analysis is combined across the Medicare and commercial markets, the loss of lead indications impacts over 15 million US patients. ConclusionsMandatory MFN policies reduce the financial incentives required to develop cancer medicines; our projections show a substantial decline in new cancer drug launches and will likely lead companies to pursue indications for populations outside Medicares authority. If so, MFN will reduce the number of new therapies for the very population the Executive Orders are allegedly designed to aid: the Medicare-aged population who require effective new therapies in areas of high unmet medical need, such as late-stage cancers. This creates the perverse outcome of a policy nominally designed to help Medicare beneficiaries by instead redirecting innovation away from their most urgent therapeutic needs.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections and hospitalizations among infants in Canada. New long-acting monoclonal antibodies (mAbs) and vaccines administered during pregnancy have expanded prevention options, yet the most cost-effective immunization program remains uncertain. MethodsWe updated a Canadian cost-utility model to evaluate seven seasonal RSV prevention strategies over one year (with a lifetime horizon for mortality impacts), from health system and societal perspectives. Strategies included RSVpreF vaccination in late pregnancy; targeted or universal infant mAb programs using nirsevimab or clesrovimab; and combination programs in which infants could receive protection from either RSVpreF or mAbs. Sequential incremental cost-effectiveness ratios (ICERs) were estimated in 2024 Canadian dollars per quality-adjusted life year (QALY), using a $50,000/QALY threshold. The primary analysis used immunization product list prices. FindingsThe most cost-effective strategy was a seasonal combination program: RSVpreF vaccination for pregnancies due during RSV season with mAb for infants at high risk (<32 weeks gestation), including catch-up for infants at high-risk born before the season. This strategy had an ICER of $35,408/QALY compared to seasonal mAb for infants at moderate risk (320/7 to 366/7 weeks gestation) or high-risk with catch-up. Expanding mAb to unimmunized non-high-risk infants born in-season increased the ICER to $132,131/QALY. Universal infant protection (mAb alone or combined with RSVpreF in pregnancy) was not cost-effective across analyses. RSVpreF alone was dominated. Results were most sensitive to product prices, target populations, age at administration, and RSV burden. ConclusionsA seasonal combination program with RSVpreF for in-season deliveries and mAb for infants at high-risk offers the best value for money for protecting Canadian infants from RSV disease. Broader infant immunization programs may be cost-effective with substantial price reductions or in regions with higher disease burden and healthcare costs.

BackgroundNorovirus vaccines are currently undergoing advanced clinical trials. Acute kidney injury (AKI) is a serious sequelae of norovirus infection. This study evaluated the health and economic impact of implementing a norovirus vaccination programme in England and assessed the contribution of AKI. MethodsWe constructed a deterministic age-stratified dynamic-transmission compartmental model. Three single-dose norovirus vaccination strategies were compared to a no-vaccination strategy: targeting children under 5 years of age, targeting adults aged 65 years or older, and targeting both age groups simultaneously. We estimated the impact on preventing primary care attendances, hospitalisations, and mortality from symptomatic norovirus, as well as hospitalisations and mortality due to norovirus-related AKI in adults aged 65 years or older. We evaluated the cost effectiveness over a 10-year time horizon, from a healthcare payer perspective, and discounted costs and quality adjusted life years (QALYs) at 3.5%. We performed probabilistic sensitivity analysis. In one-way sensitivity analysis, we varied the vaccine prices and the proportion of AKI-linked norovirus hospitalisations. ResultsA combined vaccination strategy of targeting children and older adults reduced symptomatic infections by 59% (37-84%) and 64% (39-87%) in these age groups, respectively. When including AKI outcomes, all vaccination strategies were cost-effective at {pound}35 per dose and 60% efficacy. At a willingness-to-pay of {pound}20,000 per QALY gained, the combined vaccination strategy had a 96% probability of being the most cost-effective option. Even with a norovirus-related AKI hospitalisation rate as low as 3% among symptomatic norovirus-infected adults, the strategy remained cost-effective. When excluding AKI outcomes, all strategies were not cost-effective. ConclusionsIntroducing a norovirus vaccine could be cost-effective in England when accounting for the AKI-related sequelae, which are critical for the health economic evaluation.

AimsIntravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) who are unresponsive to oral iron treatment or require rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of Chinese patients with IDA. Materials and methodsA previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with bodyweight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life was obtained from SF-36v2 data from the PHOSPHARE-IBD RCT. ResultsOver the five-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 versus 6.79). This resulted in iron procurement and administration cost savings of RMB 206 with FDI (RMB 3,519 versus RMB 3,312). Reduced incidence of hypophosphatemia resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over five years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention. ConclusionsResults showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.

BackgroundThe US Food and Drug Administration (FDA) plays a critical role in bolstering public confidence in vaccines and the vaccine review process. An important tool for enhancing transparency and public trust is the FDAs Vaccine and Biological Related Products Advisory Committee (VRBPAC), a group of external experts that advises on scientific issues related to the licensure of vaccines. ObjectiveTo analyze key features of VRBPAC meetings convened over 20 years; estimate the probability of advisory committee review of newly approved vaccines, focusing on vaccines targeting emerging diseases; and examine the speed of and variance in approval times as a function of VRBPAC review. MethodsCross-sectional study of VRBPAC meetings convened and new vaccine licensure applications approved between January 1, 2000, and December 31, 2019. We analyzed the frequency of VRBPAC meetings and sessions; the percentage of newly licensed vaccines reviewed by VRBPAC; and the number of days between the submission of the licensure application and the date of FDA approval. ResultsBetween 2000 and 2019, VRBPAC convened for a mean of 4.1 sessions per year. One-quarter of sessions was devoted to the review of specific vaccine products. During the same period, 44 new vaccine licensures were approved, 20% of which were for vaccines targeting emerging diseases. Almost half (48%) of successful new vaccine applications were reviewed by VRBPAC (n=21), a rate lower than for therapeutic applications. Among new applications targeting emerging diseases, 29% of non-influenza vaccines were reviewed by VRBPAC. There was no difference in the median time to approval as a function of VRBPAC review (364 days with VRBAC review vs. 365 days with no review, p=0.870). ConclusionThe FDA has convened VRBPAC for reviews of about half of its vaccine products, less frequently for vaccines against non-influenza emerging diseases. There is considerable scope for the FDA to increase VRBPAC engagement in the vaccine review process.