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.

ObjectivesTo assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for Fall 2023 in adults [&ge;]18 years over a 1-year analytic time horizon (September 2023-August 2024). MethodsA compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 in summer 2023. Numbers of symptomatic infections, COVID-19 related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA Fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech Fall 2023 vaccines were examined. ResultsBase case results suggest the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to No Vaccine, yielding an ICER of $7,700 per QALY gained. Using a societal cost perspective, the ICER is $2,100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates and costs drive cost-effectiveness. With a relative vaccine effectiveness (rVE) of Moderna versus Pfizer-BioNTech of 5.1% for infection and 9.8% for hospitalization, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3,300 more deaths than the Pfizer-BioNTech vaccine. Limitations and ConclusionsAs COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. Vaccine effectiveness of Fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, the Moderna Fall 2023 vaccine can be considered cost-effective relative to no vaccine.

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.

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.

BackgroundPediatric cardiology requires extensive training, yet the long-term financial implications across academic subspecialties and private practice remain poorly defined. Clearer understanding is essential for career decisions and workforce planning. MethodsWe used a net present value (NPV) framework to model lifetime earnings for pediatric cardiologists across three academic subspecialties (diagnostic, cardiac intensive care, interventional) under five promotion trajectories, comparing them with private practice. Compensation data came from the Association of Academic Administrators in Pediatrics, the Association of American Medical Colleges, and the Medical Group Management Association. Monte Carlo simulations and sensitivity analyses accounted for variation in salary percentile, discount rate, and career length. ResultsLifetime earnings were substantial across all pediatric cardiology pathways, with NPVs exceeding $7 million(M) in nearly all scenarios. Interventional cardiology yielded the highest NPV at the 50th percentile under a typical academic promotion trajectory ($7.99M), followed by cardiac intensive care ($7.76M) and diagnostic cardiology ($7.00M). Private practice produced an NPV of $7.08M at the 50th percentile, with a ramp-up model increasing this to $7.30M; still below interventional and CICU academic tracks. Academic earnings increased by up to $2.44M through early promotion compared to no promotion, and by up to $867,000 through leadership roles, depending on subspecialty. Salary percentile was the most influential NPV driver; interventional cardiology at the 90th percentile exceeded $10.4M, and private practice reached $10.76 million. Private practice exhibited the widest lifetime earnings range. ConclusionsPediatric cardiologists, particularly those in interventional subspecialties or academic leadership, achieve substantial lifetime earnings. At the 50th percentile, academic and private practice careers offer comparable financial outcomes, but private practice shows greater variability. Optimizing academic pathways through early promotion, high-percentile salaries, or leadership roles can match or exceed private practice. These findings can guide trainees and inform institutional strategies for recruitment, and compensation equity in pediatric cardiology. What is KnownO_LIPediatric subspecialists, including cardiologists, have historically reported lower compensation than adult medicine counterparts. C_LIO_LILifetime earning disparities across the pediatric workforce are documented, but subspecialty-specific financial outcomes within pediatric cardiology remain uncharacterized. C_LI What the Study AddsO_LIApplies a net present value framework with Monte Carlo simulations to model lifetime earnings across academic pediatric cardiology subspecialties and private practice. C_LIO_LIDemonstrates that academic pediatric cardiology, especially interventional and CICU tracks, can achieve lifetime earnings comparable to or greater than private practice. C_LIO_LIIdentifies promotion timing, leadership roles, and higher salary percentiles as major modifiable drivers of lifetime earnings, providing actionable insights for trainees and institutions. C_LI

ObjectiveThis study aims to assess the cost-effectiveness of the Fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine. MethodsA one-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no Fall 2023 vaccination, BNT162b2 vaccination and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness. ResultsIn the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 ICU admissions), 207 deaths, and 2,124 post-COVID cases. Societal cost savings were {euro}12.9million (excluding vaccination costs), with 1,506 QALYs gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was {euro}16.72 or {euro}34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained. ConclusionThis study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization programme in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most {euro}34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.

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.

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.

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.

We discuss tradeoffs and errors associated with approaches to modeling health economic decisions. Through an application in pharmacogenomic (PGx) testing to guide drug selection for individuals with a genetic variant, we assessed model accuracy, optimal decisions and computation time for an identical decision scenario modeled four ways: using (1) coupled-time differential equations [DEQ]; (2) a cohort-based discrete-time state transition model [MARKOV]; (3) an individual discrete-time state transition microsimulation model [MICROSIM]; and (4) discrete event simulation [DES]. Relative to DEQ, the Net Monetary Benefit for PGx testing (vs. a reference strategy of no testing) based on MARKOV with rate-to-probability conversions using commonly used formulas resulted in different optimal decisions. MARKOV was nearly identical to DEQ when transition probabilities were embedded using a transition intensity matrix. Among stochastic models, DES model outputs converged to DEQ with substantially fewer simulated patients (1 million) vs. MICROSIM (1 billion). Overall, properly embedded Markov models provided the most favorable mix of accuracy and run-time, but introduced additional complexity for calculating cost and quality-adjusted life year outcomes due to the inclusion of "jumpover" states after proper embedding of transition probabilities. Among stochastic models, DES offered the most favorable mix of accuracy, reliability, and speed.

This note estimates the costs and benefits of a nationwide COVID-19 screening testing program in the presence of vaccine distribution. Even for an optimistic vaccine rollout scenario, a well-designed federally-funded screening testing program, coupled with self-isolation of those who test positive, pays for itself in terms of increased GDP and is projected to save 20,000 or more lives. The sooner the testing program is put in place, the greater are its net economic benefits. This note updates the December 9, 2020 version to include updated deaths data, later dates for rolling out the screening testing program, and the spread of more contagious variants such as the B.1.1. 7 variant.

ObjectiveTo evaluate the impact of implementing pediatric medication pathways on operational management under the DRG/DIP payment model in a specialized childrens hospital, using DRG as a case study. MethodsAll medical records with DRG codes DT13 and GW15 from 2023 (pre-implementation control group) and 2024 (post-implementation observation group) were included. A systematic comparative analysis of clinical data was performed to assess the effects on hospital operational metrics. ResultsThe observation group exhibited a significantly lower average cost per case (DT13: 17.82%; GW15: 26.05%) and a higher medical insurance payment margin (DT13: {yen}186,500; GW15: {yen}89,000) compared to the control group. The examination cost proportion and total hospitalization expenses decreased significantly (P < 0.05), whereas the drug cost proportion showed a non-significant decreasing trend (P > 0.05). Regarding efficiency, the average length of stay and number of drug varieties were significantly reduced (P < 0.05). Quality indicators, including antibiotic usage rate, antibiotic use intensity, and adverse drug reaction incidence, were significantly improved (P < 0.05), alongside an increased rational prescription review rate. Furthermore, the number of high-cost cases decreased while low-cost cases increased for both disease groups post-implementation, with all case distributions remaining within clinically acceptable bounds. ConclusionPediatric medication pathways represent an effective strategy for balancing cost-containment with the unique clinical demands of pediatric care within the DRG/DIP framework. They provide a practical reference for precision management in pediatric hospitals and empirical evidence to inform pediatric-sensitive medical insurance payment policies.

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.

BackgroundTwo prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against Respiratory Syncytial Virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines. MethodsWe developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the US. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-years (QALY) gained as a measure of effectiveness, and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective. ResultsUsing a willingness-to-pay of $95,000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD under $120 with Arexvy and $111 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the US, the budget impact of these programs at the maximum PPD ranged from $5.74 to $6.10 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $250 for Arexvy and $233 for Abrysvo, with two-year budget impacts of $11.59 and $10.89 billion, respectively. ConclusionsVaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population.

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.

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.

Executive summaryThe paper presents the methodology and modeling results for COVID-19 vaccines portfolio forecasting, including R&D output (rate and likelihood of approvals at a vaccine technology platform level) and manufacturing production output to meet worldwide demand. In order to minimize the time and risk of global vaccination, scaling up of Operation Warp Speed (OWS) and other programs could be very beneficial, leading to increased financing for additional vaccine development programs, in both Phase III clinical trials and in manufacturing. It would also lead to a reduction of the global production time for world vaccination, from 75 months for a baseline scenario to 36 months, reducing potential global GDP loss by as much as US$4.2 trillion (US [~] $1 trillion) when compared to the baseline scenario.

AimTo explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared to children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs). MethodsIn 34,214 children aged 1 month to 5 years who were registered with one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 (N=128), RSV infection (N=4,009), or other RTIs (N=34,458) from 2017-2021, we used a difference-in-differences study design to investigate the individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified on infants (1-12 months) and children (1-5 years). ResultsWe found a slight increase in primary health care use in the first four weeks after the hospital visit for infants with COVID-19 when compared to infants with RSV infection (6 [95%CI=2 to 13] per 10,000, 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared to infants with RSV infection, which lasted for 12 weeks. ConclusionsOur findings imply slightly increased health care use among infants after hospital visit for COVID-19 than among infants with other respiratory tract infections, for which potential etiological mechanisms deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services.