Journal of Medical Economics

AimsCOVID-19 disease burden in United States (US) adults [≥]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 [≥]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.

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.

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.

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.

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.

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.

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.

Breast cancer was the leading cause of cancer-related mortality among women worldwide in 2022. In Kenya, more than a quarter of breast cancer patients have the aggressive Human Epidermal Growth Factor Receptor 2 positive subtype. Trastuzumab is recommended for its treatment, but high costs have limited access. This study evaluated the cost-effectiveness and affordability of trastuzumab-based regimens to inform their adoption and use in Kenya. A cost-utility analysis was conducted from the healthcare payer perspective over a lifetime horizon. Five trastuzumab-based regimens of varying durations (9-week, 6-month, 9-month, 12-month, and 24-month) were compared with chemotherapy alone. Direct medical costs were estimated using a bottom-up micro-ingredient approach. All costs were reported in 2022 USD. A cohort Markov state-transition model with a monthly cycle length was used to estimate the costs and outcomes for an open hypothetical cohort. Scenario, deterministic sensitivity and probabilistic sensitivity analyses were conducted. A budget impact analysis estimated the financial implications of each regimen. The 9-week regimen had the lowest incremental cost-effectiveness ratio (ICER) of USD 3,230 per QALY, while the remaining regimens had ICERs ranging from USD 4,046 to 9,846 per QALY. The findings were most sensitive to the price and quantity utilized per cycle of trastuzumab. A reimbursement cap of KES 40,000 per cycle reduced ICERs by up to 61%. Over five years, the 9-week regimen would account for 1.2% of the projected insurers budget, whereas the current recommended 12-month regimen would consume 2.82%. Although none of the regimens were cost-effective at Kenyas WTP threshold (USD 1054.80), the 9-week regimen may still be considered by policymakers given its greater affordability. Further cost reductions can be achieved through negotiating lower drug prices, improving access to biosimilars, and implementing vial sharing.

This study analyzed the effects of patent expiration on drug prices in eight countries (US, UK, Cana-da, Australia, Japan, France, Germany, and Switzerland) and the impact of these price dynamics in cost-effectiveness assessments. First, using an event study design, we showed that average prices of drugs substantially decreased eight years after patent expiration. Then, to assess the implications of this finding for cost-effectiveness assessments, a theoretical cost-effectiveness model simulated two real-world scenarios: (1) the comparator drug was a generic and the patent of the new drug expired after market entry; (2) the comparator drug was also under patent protection, but the patent expired prior to the patent of the new drug. Not accounting for genericization or patent expiration of the com-parator drug resulted in an underestimation or overestimation of the incremental cost-effectiveness ratios, respectively. Our pricing dynamic estimates can be applied to base-case analyses of cost-effectiveness models.

BackgroundIn the United States (US), three vaccines are currently available for primary vaccination and booster doses to prevent coronavirus disease 2019 (COVID-19), including the 2-dose messenger ribonucleic acid (mRNA) BNT162b2 (COMIRNATY(R), Pfizer Inc) and mRNA-1273 (SPIKEVAX(R), Moderna Inc) vaccines, which are preferred by the Centers for Disease Control and Preventions (CDC) Advisory Committee on Immunization Practice (ACIP), and the adenovirus vector Ad26.COV2.S (Johnson & Johnson) vaccine. A substantial body of evidence has now been published on the real-world effectiveness and waning of the primary series and booster doses against specific SARS-CoV2-variants. The study objective was to determine the clinical and economic impact of differences in effectiveness between mRNA-1273 and BNT162b2 booster vaccinations over one year (2022) in US adults [&ge;]18 years. MethodsA decision analytic model was used to compare three mRNA booster market share scenarios: (1) Current Scenario, where the booster mix observed in December 2021 continues throughout 2022; (2) mRNA-1273 Scenario, where the only booster administered in 2022 is mRNA-1273, and (3) BNT162b2 Scenario, where the only booster administered in 2022 is BNT162b2. Analyses were performed from the US healthcare system perspective. Sensitivity analyses were performed to explore the impact of COVID-19 incidence in the unvaccinated population and vaccine effectiveness (VE) on model results. ResultsIn the Current Scenario, the model predicts 65.2 million outpatient visits, 3.4 million hospitalizations, and 636,100 deaths from COVID-19 in 2022. The mRNA-1273 Scenario reduced each of these outcomes compared to the Current Scenario. Specifically, 684,400 fewer outpatient visits, 48,700 fewer hospitalizations and 9,500 fewer deaths would be expected. Exclusive of vaccine costs, the mRNA-1273 Scenario is expected to decrease direct medical costs by $1.3 billion. Conversely, the BNT162b2 Scenario increased outcomes compared to the Current Scenario: specifically, 391,500 more outpatient visits, 34,500 more hospitalizations and 7,200 more deaths would be expected in 2022, costing an additional $946 million in direct medical costs. For both the mRNA-1273 and BNT162b2 booster scenarios, the percent change in direct treatment costs for COVID-19 is similar to the percent change in hospitalizations as the rate of hospitalizations is the driver of the overall costs. Changing the number of projected COVID-19 cases in 2022 by varying the incidence rate has a direct effect on model outcomes. Higher incidence rates leads to higher outpatient visits, hospitalizations and deaths for all scenarios. Varying VE has an inverse effect on model outcomes. All outcomes increase when VE is lower for all vaccines and decrease when VE is higher. In all cases, additional use of mRNA-1273 leads to fewer infection outcomes while additional use of BNT126b2 results to higher infection outcomes. ConclusionAs the real-world effectiveness evidence to date indicates that mRNA-1273 may be more effective at preventing COVID-19 infection and hospitalization over time than BNT-162b2, increasing the proportion of people receiving this as a booster are expected to reduce COVID-19-related outcomes and costs in 2022, regardless of COVID-19 incidence or variant.

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.

BackgroundCell and gene therapies (CGT) represent a transformative class of medical interventions, yet their high production costs limit patient access. Understanding the structure of manufacturing costs is essential for informing policies that can expand access to these therapies. ObjectiveThis study develops and applies a cost-of-goods-sold (COGS) model to analyze the contributors to manufacturing costs for mRNA-based CGT, with application to a wide range of current and future therapies. MethodsAn Excel-based COGS model was constructed based on cost categories for CGT. Two mRNA-based products at commercial scale were used to populate the model: an mRNA vaccine and a therapeutic mRNA gene therapy. Cost inputs were drawn from vendor pricing, peer-reviewed and grey literature, and expert consultation with CGT manufacturing specialists. Three scenarios (worst, base, and best case) were modeled across six cost categories: materials, consumables, capital, labor, licenses, and royalties. A tornado diagram sensitivity analysis was conducted to identify key cost drivers. The mRNA vaccine was used to build and validate the model strucutre using publicly available data sources. The therapeutic mRNA therapy was used as the main use case for illustration and sensitivity analysis. ResultsUnder base-case assumptions, the estimated cost per dose for the therapeutic mRNA product is $56.09, ranging from $3.68 (best case) to $383.22 (worst case). Licensing and royalty fees together account for approximately 83% of total base-case COGS ($6,996,000 and $6,960,000 per production run, respectively, out of $16,825,597 total). Excluding these fees, material costs represent the largest remaining share (61%), followed by consumables (34%), capital (4%), and labor (1%). Sensitivity analysis confirms that licensing and royalty assumptions are the dominant source of uncertainty in the model. ConclusionsLicensing and royalty fees are the primary driver of mRNA-based CGT production costs and represent the greatest opportunity for cost reduction through policy intervention. Strategic priorities for cost reduction should focus on optimizing reagent utilization, increasing platform potency, and expanding use of contract development and manufacturing organizations (CDMOs) to reduce capital and labor costs. Key PointsProducing an example mRNA gene therapy costs about $56 per dose to manufacture, driven almost entirely driven by fees paid to patent holders for the underlying technology. Licensing and royalty fees cost roughly 83 cents of every dollar spent on these new biopharmaceutical products. Until that changes, the gap between what therapies cost to make and what patients and payers are charged will remain very wide.

Although various COVID-19 vaccines have shown efficacy against placebo in randomized clinical trials, no head-to-head comparisons are yet available. This study aims to compare the efficacy of available COVID-19 vaccines. Vaccine trials searched in May 2021 were included. Data were extracted from Kaplan-Meier (KM) curves using the WebPlotDigitizer program for the individual participant (IP) data simulation. A mixed-effect acceleration failure model with log-logistic and Weibull distributions was used to estimate relative effects for individual vaccines as well as grouped by class: inactivated virus, mRNA, and viral vector. Primary studies were considered as the random effect in the model. Hazard ratios (HR) were estimated and compared across vaccine groups. All vaccines were efficacious in lowering symptomatic infection compared to placebo. CoronaVac, Ad26.COV2.S, ChAdOx1 nCoV-19, rAd26/rAd5, WIV04, HB02, and BNT162b2 showed 7.61 (4.50, 12.87), 6.77 (4.08, 11.24), 5.01 (2.93, 8.57), 4.50 (2.52, 8.01), 3.90 (2.04, 7.45), 3.18 (1.62, 6.21), and 2.15 (1.22, 3.78) times significantly higher risk of infection than mRNA-1273. mRNA vaccines were the most efficacious vaccine group compared to inactivated virus and viral vectors with HRs (95% CI) of 0.27 (0.20, 0.37) and 0.28 (0.21, 0.37), respectively. Although all vaccines showed significant protection compared to no vaccination. mRNA vaccines, including mRNA-1273 and BNT162b2, showed the highest efficacy in preventing symptomatic COVID-19 infection. Simulated IP data from the KM curve might allow treatment comparison when there is no primary study comparing active treatments.

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 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.

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.

BackgroundThe United Nations General Assembly High-level Meeting on Antimicrobial Resistance (UNGA HLM-AMR) committed to a target that 70% of global human antibiotic use (ABU) should be from the Access group of the WHO AWaRe system. MethodsWe used 2019 IQVIA MIDAS(R) global ABU Quarterly value sales, volumes (kg/SU) and average ex-manufacturer prices to evaluate price per daily defined dose (DDD) by AWaRe group across countries. IQVIA MIDAS volumes/value data reflect public, private, or mixed sectors. We estimated potential national pharmaceutical expenditure savings if i) the UNGA 70% Access target was met, and ii) national ABU aligned with the WHO Model List of Essential Medicines (EML). We evaluated 7-day treatment prices for common oral and parenteral antibiotics across AWaRe groups. We measured affordability in middle-income countries (MICs) by income group, as the percentage of the population at risk of falling below national poverty lines if paying out-of-pocket, using income distributions and generalised beta distributions of the second kind. Prices were reported in 2019 international dollars (I$). ResultsVolume-weighted ex-manufacturer prices per DDD were lower for Access (I$1{middle dot}2, IQR I$0{middle dot}7) than Watch (I$2{middle dot}6, IQR I$2{middle dot}1) and highest (I$83{middle dot}8, IQR I$80{middle dot}9) for Reserve antibiotics. Lower prices were seen in high-income countries for Access antibiotics. Meeting the 70% Access target could save countries I$0{middle dot}1 million-I$4{middle dot}9 billion annually. Global savings could reach I$10{middle dot}4 billion if only WHO EML-listed antibiotics were used. Seven-day parenteral meropenem could put 7% (IQR 9%) of the population in MICs at risk of impoverishment. ConclusionAntibiotic policies focused on achieving the UNGA-AMR 70% Access target could generate significant potential national and global expenditure savings. FundingThis work was supported by the Wellcome Trust (304681/Z/23/Z) as part of the Antibiotic Data to Inform Local Action (ADILA) project and the Global Antibiotic Policy initiative (GAPi) project (RES 2024-495).

BackgroundFierce debate about the health and financial tradeoffs presented by different COVID-19 pandemic mitigation strategies highlights the need for rigorous quantitative evaluation of policy options. ObjectiveTo quantify the economic value of the costs and benefits of a policy of continued limited reopening with social distancing relative to alternative COVID-19 response strategies in the United States. DesignWe estimate the number and value of quality-adjusted life-years (QALY) gained from mortality averted, with a value of $125,000 per QALY, and compare these benefits to the associated costs in terms of plausible effects on US GDP under a policy of continued limited reopening with social distancing relative to a policy of full reopening toward herd immunity. Using the same QALY value assumptions, we further evaluate cost-effectiveness of a return to Shelter-in-Place relative to a policy of limited reopening. SettingUnited States MeasurementsQALY and cost as percent of GDP of limited reopening with continued social distancing relative to a strategy of full reopening aimed at achieving herd immunity; a limited reopening "budget" measured in the number of months before this strategy fails to demonstrate cost-effectiveness relative to a full reopening; a shelter-in-place "threshold" measured in the number of lives saved at which a month of sheltering in place demonstrates cost effectiveness relative to the limited reopening strategy. ResultsQALY benefits from mortality averted by continued social distancing and limited reopening relative to a policy of full reopening exceed projected GDP costs if an effective vaccine or therapeutic can be developed within 11.1 months from late May 2020. White House vaccine projections fall within this date, supporting a partial reopening strategy. One month of shelter-in-place restrictions provides QALY benefits from averted mortality that exceed the associated GDP costs relative to limited reopening if the restrictions prevent at least 154,586 additional COVID-19 deaths over the course of the pandemic. Current models of disease progression suggest that limited reopening will not cause this many additional deaths, again supporting a limited reopening strategy. LimitationLimited horizon of COVID-19 mortality projections; infection fatality ratio stable across strategies, ignoring both the potential for ICU overload to increase mortality and the deployment of partially effective therapeutics to decrease mortality; effect on GDP modeled as constant within a given phase of the pandemic; accounts for age and sex distribution of QALYs, but not effect of comorbidities; only considers impact from QALY lost due to mortality and from changes in GDP, excluding numerous other considerations, such as non-fatal COVID-19 morbidity, reduced quality of life caused by prolonged social distancing, or educational regression associated with prolonged school closures and restrictions. ConclusionsA limited reopening to achieve partial mitigation of COVID-19 is cost effective relative to a full reopening if an effective therapeutic or vaccine can be deployed within 11.1 months of late May 2020. One additional month of shelter-in-place restrictions should only be imposed if it saves at least 154,586 lives per month before the development of an effective therapeutic or vaccine relative to limited reopening. FundingThis work was supported in part by grant K01AI119603 from the National Institute of Allergy and Infectious Diseases (NIAID). This work does not necessarily represent the opinions of the NIAID, the NIH, or the United States Government.

Background Catch-up vaccination will be pivotal for achieving WHOs cervical cancer elimination goals in low- and middle-income countries (LMICs). We assessed the health-economic impact of catch-up HPV vaccination for females in LMICs. Methods Using IARCs METHIS modelling platform and data from 132 LMICs, we simulated HPV catch-up vaccination beyond the primary target age, varying the maximum age up to 30 years. Budget impact was expressed as a share of national five-year immunization budgets and current health expenditure. We conducted cost-effectiveness analyses for a smaller subset of countries for which high-quality cervical cancer treatment costs were available. Findings Catch-up HPV vaccination up to age 30 in LMICs could prevent 9.2 million cervical cancer cases over the lifetime among females aged 9-30 years. Across countries, budget impact ranged from 0.007%-2.24% of five-year health expenditure and 0.002%-236.65% of immunization budgets, with vaccine procurement comprising about 70% of costs. Gavi support could reduce costs by nearly 70% for catch-up up to age 18. Catch-up vaccination up to age 30 was cost-effective in almost all evaluated countries, except in one where cost-effectiveness was achieved up to age 21. Interpretation In LMICs, after achieving adequate coverage in the primary target group (9-14 years), expanding HPV catch-up vaccination would be impactful and cost-effective. Sustainable financing, Gavi support, and cost-minimization strategies are crucial for successful catch-up programmes and progress toward cervical cancer elimination.

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.