The Epidemiological and Economic Impact of a Cell-Based Quadrivalent Influenza Vaccine in Adults in the US: A Dynamic Modeling Approach

Abstract

Mutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process partly explain the suboptimal effectiveness of traditional seasonal influenza vaccines. Cell-based influenza vaccines improve antigenic match and vaccine effectiveness by avoiding such egg-adaptation. This study evaluated the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adults (18–64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe) in the US. The impact of QIVc over QIVe in public health and cost outcomes was estimated using a dynamic age-structured SEIR transmission model, which accounted for four circulating influenza strains [A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)] and was calibrated on the 2013–2018 influenza seasons. The robustness of the results was assessed in univariate and probabilistic sensitivity analyses. Switching from QIVe to QIVc in 18- to 64-year-olds may prevent 5.7 million symptomatic cases, 1.8 million outpatient visits, 50,000 hospitalizations, and 5453 deaths annually. The switch could save 128,000 Quality-Adjusted Life Years (QALYs) and US $ 845 M in direct costs, resulting in cost-savings in a three-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result. The analysis shows that QIVc is expected to prevent hospitalizations and deaths, and result in substantial savings in healthcare costs.

The economic rationale for cell-based influenza vaccines in children and adults: A review of cost-effectiveness analyses

“…WTP threshold was CA$50,000 Replacing QIVe with QIVc in individuals 6 months–64 years of age (and aTIV with those ≥65 years of age) is cost-effective across varying assumptions of rVE and numbers of egg-adapted influenza seasons. Sensitivity analysis shows that this vaccine combination would be favorable in nearly all scenarios Nguyen et al, 2021 32 United States Adults 18–64 years of age Compared with QIVe for the entire population, the authors estimated the CE of QIVc in those 18–64 years of age Dynamic age-structured SEIR transmission model Societal 3 years QIVe = $17.22QIVc = $24.22 Hospitalization, GP visit Lostwork days US Dollar ($), year not reported QIVc versus QIVe was 26.8% (95% CI: 14–37) 26 Life years and QALYs lost were discounted PSA QIVc was dominant (ICER –$10,400/QALY). Base case scenario assumed 3 years of mismatch out of 5 years QIVc was more effective and cost-saving than QIVe, validated by sensitivity analyses Chi et al, 2023 33 Taiwan Children and adolescents 6 months–17 years of age Replacing QIVe with QIVc in children and adolescents 6 months–17 years of age 1-year age-stratified static decision tree Payer and societal perspective (two base case analyses) 1 year QIVc unit cost assumed 25% higher than QIVe Outpatient, ER visit, hospitalization, transportation costs Loss of productivity US Dollar ($), 2022 QIVc versus QIVe against all influenza strains was 8.1% 34 3% annualized inflation rate applied DSA and PSA ICER was $68,298/QALY and $40,085/QALY from payer and societal perspectives, respectively.…”

“…Estimates of rVE of QIVc versus QIVe applied in the CEA studies ranged from 8.1% to 36.2%, with a trend toward lower estimates applied in more recent CEAs. The three most recent CEAs used rVE data from meta-analysis estimates, 33–35 and several other analyses included a base case rVE point estimate originating from the 2017–2018 egg-adapted season 25 , 27 , 29 , 30 , 32 ( Table 2 ), which was characterized as a high-severity season with documented evidence of egg-adapted mutations in the egg-based vaccine A(H3N2) strain dominated by A(H3N2) and B strains.…”

“…Some variation in rVE point estimates between models can be attributed to differences in populations assessed, different influenza endpoints assessed, and different methodologies used to generate estimates, including data from single-season retrospective cohorts, data from different influenza seasons, pooled RWE estimates from multiple seasons, and point estimates from meta-analyses. The highest rVE values of 26.8% and 36.2% used in five CEAs 25 , 27 , 29 , 30 , 32 were based on RWE from the 2017–2018 season, 26 , 28 which was characterized as a high-severity influenza season with egg-adapted vaccine-mismatch dominated by A(H3N2) and B strains. Influenza A(H3N2) can be particularly affected by egg adaptation and is a strain that can be associated with high rates of illness, medical visits, and hospitalization, especially in those ≥50 years of age.…”

Cost-Effectiveness Analysis of Cell Versus Egg-Based Seasonal Influenza Vaccination in Children and Adults in Argentina

“…The cost-effectiveness of QIVc has been reported for the United States (US) [ 16 , 17 ], Spain [ 18 ], Brazil [ 19 ], the United Kingdom (UK) [ 20 ], and Germany [ 21 ]. In the UK, Kohli et al reported the cost-effectiveness of extending QIVc vaccination regimen from at-risk to low-risk adults between 50 and 64 years of age [ 20 ].…”

Pediatric Vaccines:

“…Preparation in this way promotes fewer instances of antigenic mismatch, raising vaccine efficacy. 4 The Pfizer-BioNTech (BNT162b2) COVID-19 vaccine was also approved for use in pediatric patients 5 to 18 years of age in 2021. Trials are still ongoing for pediatric patients 6 months through 4 years of age.…”