Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France (preprint)

An economic evaluation was conducted to predict the economic and clinical burden of vaccinating immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines in Fall 2023 and Spring 2024 versus BNT162b2 variant-adapted vaccines in France. The number of symptomatic COVID-19 infections, hospitalizations, deaths, and long COVID cases, costs and quality-adjusted life years (QALYs) was estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from prior versions, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were tested in sensitivity analyses. The mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs saved. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.

The potential economic impact of the updated COVID-19 mRNA fall 2023 vaccines in Japan (preprint)

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults at least 18 years in Japan. A previously developed Susceptible Exposed Infected Recovered (SEIR) model with a 1 year analytic time horizon (September 2023 to August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID19 related hospitalizations, deaths, quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was 1,300,000 Yen/QALY gained ($9,400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID 19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2,600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost effective at a 5 million Yen willingness to pay threshold across a wide range of scenarios.

Clinical and Economic impact of updated Fall 2023 COVID-19 vaccines in the Immunocompromised Population in Canada (preprint)

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 [≥]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.

Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 Vaccine (preprint)

Background: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a Fall 2023 COVID-19 vaccine for adults 18 years and older on these outcomes. Methods: A previously developed Susceptible Exposed Infected Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19 related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. Results: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial vaccine effectiveness (VE) against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. Conclusions: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19 related infections, hospitalizations, and deaths.

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany (preprint)

Objectives: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged [≥]60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023--August 2024). Methods: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, number of COVID-19 related hospitalisations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. Results: Compared to no Autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalisations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalisations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. Conclusions: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.

The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA Fall 2023 vaccines in the United States (preprint)

Objectives: To assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for Fall 2023 in adults [≥]18 years over a 1-year analytic time horizon (September 2023-August 2024). Methods: A 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. Results: Base 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 Conclusions: As 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.

Impact of Differential Vaccine Effectiveness on COVID-19 Hospitalization Cases: Projections for 10 Developed Countries where Booster Vaccines were Recommended (preprint)

Background & Objectives: In 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. Methods: The 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. Results: The 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. Conclusions: Real-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.

The Potential Clinical Impact of Implementing Different COVID-19 Boosters in Fall 2022 in the United States (preprint)

Objective Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for the fall vaccination strategy. We aimed to estimate the number of infections and hospitalizations prevented by three potential booster strategies in those ≥18 years of age in the United States: Boosting with Moderna’s licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) starting in September 2022, boosting with Moderna’s candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or boosting with Moderna’s updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting 2 months later in November 2022 due to longer development timeline. Methods An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate the number of infections over time; the model contains compartments defined by both SEIR status and vaccination status. A decision tree was subsequently used to estimate the clinical consequences of those infections. Calibration was performed so the model tracks the actual course of the pandemic up to the present time. Results Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, over a 6-month time horizon (September-February) compared to no booster. Similarly, boosting in September prevents substantially more hospitalizations than starting to boost in November with a more effective vaccine (42%, 48%, and 25% for mRNA-1273, mRNA-1273.214, and mRNA-1273.222, respectively, at 6 months compared to no booster). Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning of natural and vaccine-induced immunity changed the magnitude of cases prevented but boosting with mRNA-1273.214 in September consistently prevented more cases of infection and hospitalization than the other two strategies. Limitations and Conclusions With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making estimation of these parameters difficult, especially in heterogeneous populations. Our analysis demonstrated that vaccinating with the bivalent mRNA-1273.214 booster was more effective over a 6-month period in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

Clinical and Economic Impact of Differential COVID-19 Vaccine Effectiveness in the United States (preprint)

Background: In 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 Prevention's (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 [≥]18 years. Methods: A 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. Results: In 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. Conclusion: As 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.