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

Figures & data

Figure 1. CE of QIVc vs QIVe, itemized by study perspective, time horizon, population and estimated local willingness-to-pay threshold.^{25,27,29–35}

Table 1. CEA of QIVc versus QIVe.

Author, year	Country	Population	Strategy	Model type	Perspective	Time horizon	Selected costs	Currency, year	rVE, base case	Discounting	Uncertainty analysis	Findings	Author conclusion
Ballalai et al., 2021^Citation25	Brazil	≥6 months	Replacing TIVe with QIVc	Static decision-tree model	Payer, societal (two base case analyses)	1 year	TIVe = R$15.12 QIVc = R$46.73 Hospitalizations Outpatient costs Lost productivity	Brazilian Real (R$), 2019	rVE of QIVc versus TIVe against influenza A(H3N2) = 36.2%^Citation26	No discount applied due to the short duration of analysis	DSA and PSA	ICER of R$17,293/QALY payer perspective; R$16,669/QALY societal perspective WTP estimate R$34,533	Replacing TIVe with QIVc in Brazil is predicted to be cost-effective from both a payer and societal perspective
Rizzo et al., 2019^Citation27	Italy	6 months–8 years, 9–17 years, and 18–64 years	QIVe was replaced with QIVc in individuals 9–64 years of age	Deterministic SEIR model	National health service (base case), societal	1 year	QIVe = €5.50 QIVc = €8.00 Hospitalization Absenteeism	Euros (€), 2018	QIVc versus QIVe against A(H3N2) = 36.2% for those >9 years of age^Citation28	No discount applied for annual vaccination Outcomes 3%	PSA	From the health service perspective, QIVc had an ICER €2,872/QALY for those 18–64 years of age and was dominant in other age groups. From the societal perspective, QIVc was dominant in those 6 months–8 years, 9–17 years, and 18–64 years of age. QIVc remained cost-effective up to €18.70. WTP threshold was €30,000/QALY	Replacing QIVe with QIVc in Italian individuals 9–64 years of age is highly cost-effective or cost-saving (dominant), depending on the perspective and age range. QIVc remained highly cost-effective, even in the worst-case scenarios
Cai et al., 2021^Citation29	Germany	Individuals ≥9 years of age	QIVe replaced with QIVc in individuals ≥9 years of age	Adapted dynamic 4Flu transmission, combined with decision-tree	Societal and payer perspectives	20 years	QIVe = €11.60 QIVc = €12.50 Hospitalizations, GP visits, complications Absenteeism, patient transportation costs, child sickness benefit cost, loss of productivity	Euros (€), 2019	QIVc versus QIVe against A(H3N2) = 36.2% for years with egg adaptation^Citation28	Costs and outcomes 3%	DSA and PSA	From a societal perspective (base case), QIVc was dominant in settings of 100% and 55% egg adaptation. From a payer perspective, ICER was €2,285–€8,984/QALY with rVE 36.2%, and ICER was €8,199–€22,845/QALY with rVE 19.3%. WTP threshold was €30,000/QALY	The use of QIVc compared with QIVe in the German Immunization Program could significantly prevent outpatient visits and hospitalizations and would enable substantial savings from a societal perspective
Ruiz-Aragón et al., 2020^Citation30	Spain	Individuals 9–64 years of age at high risk of complications	QIVe replaced with QIVc in those 9–64 years of age	Static decision-tree model	Societal and public payer perspectives	1 year	QIVe = €6.00 QIVc = €7.50 GP visit, ER visit, hospitalization Loss of productivity	Euros (€), year not reported	QIVc versus QIVe = 26.8%, assumed the same across all influenza strains and ages, and between high-risk and low-risk groups^Citation28	Public payer costs not discounted as they were only calculated over 1 year Societal costs and QALY loss due to death were calculated according to life expectancy and discounted at 3% per year	DSA and PSA	From the payer perspective, the ICER was €12,852/QALY. From a societal perspective, QIVc was dominant. WTP threshold was €22,000–€25,000/QALY	Switching from QIVe to QIVc was cost-effective from the payer perspective and cost-saving from the societal perspective (due to reduction in symptomatic cases and workdays lost) and would considerably reduce the burden of disease due to influenza in a large segment of the Spanish population
Nguyen and Roy, 2022^Citation31	Canada	Entire population	Compared cost-effectiveness of QIVe for all versus QIVc in persons <65 years of age (and aTIV with those ≥65 years of age)	Age-structured SEIR dynamic-transmission model	N/A	8 years (2012–2019), during which there were six egg-adapted seasons (2012–2014, 2016, 2017, and 2019)	Vaccine costs were list prices according to the Quebec Government as of 2021 Assumed 50% of children <3 years of age require two doses Hospitalization, ER visit, ICU, mechanical ventilation	Canadian Dollar(CA$), year not reported	QIVc versus QIVe against influenza A(H3N2) was 15.6% in seasons with egg-adaptation	5% outcomes across time horizon of 8 years	PSA	QIVc (and aTIV with those ≥65 years of age) resulted in an ICER of CA$1,300/QALY at a rVE of 15.6%, and an ICER of CA$6,900/QALY at an rVE of 7.6%. 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^Citation32	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)^Citation26	Life years and QALYs lost were discounted	PSA	QIVc was dominant (ICER –$10,400/QALY). Base case scenario assumed 3 years of mismatch out of 5 years	QIVc was more effective and cost-saving than QIVe, validated by sensitivity analyses
Chi et al., 2023^Citation33	Taiwan	Children and adolescents 6 months–17 years of age	Replacing QIVe with QIVc in children and adolescents 6 months–17 years of age	1-year age-stratified static decision tree	Payer and societal perspective (two base case analyses)	1 year	QIVc unit cost assumed 25% higher than QIVe Outpatient, ER visit, hospitalization, transportation costs Loss of productivity	US Dollar ($), 2022	QIVc versus QIVe against all influenza strains was 8.1%^Citation34	3% annualized inflation rate applied	DSA and PSA	ICER was $68,298/QALY and $40,085/QALY from payer and societal perspectives, respectively. WTP threshold was $99,177/QALY	Switching from QIVe to QIVc in Taiwanese children and adolescents is predicted to significantly reduce the influenza-associated disease burden and be cost-effective in Taiwan. The predicted benefits of QIVc may be even higher in seasons with egg adaptation
Pelton et al., 2024^Citation35	United States	Children (6 months–17 years of age) and adults (18–64 years of age)	Replacing QIVe with QIVc in individuals 6 months–64 years of age. High- and low-incidence influenza seasons were evaluated	Dynamic age-structured SEIR transmission model	Payer and societal perspectives	1 year	Vaccine costs in individuals 6 months–17 years of age: $29.88 QIVe, $42.66 QIVcVaccine costs in individuals 18–64 years of age: $19.92 QIVe, $28.44 QIVcGP consultation, hospitalizationLoss of productivity	US Dollar ($), year not reported	QIVc versus QIVe was 8.1% for children and 11.4% for adults^Citation34	3% life years gained	DSA and PSA	QIVc was dominant. In a high-incidence season, ICER was –$8,100/QALY and –$15,015/QALY from payer and societal perspectives, respectivelyIn a low-incidence season, ICER was –$16,427/QALY and –$22,669/QALY from payer and societal perspectives, respectively. WTP threshold was $50,000/QALY	In both low- and high-incidence seasons, QIVc would be a cost-saving strategy, with savings from societal and payer perspectives. Sensitivity analysis indicated that QIVc would be cost-effective in > 95% of simulations.
Urueña et al., 2022^Citation34	Argentina	Children (6 months–2 years of age) and at-risk individuals (2–64 years of age)	Replacing QIVe with QIVc in children and adults in base case and high egg-adaptation scenarios	Analytical static decision-tree model	Payer (base case) and societal perspectives	1 year	Vaccine costs were $6.27 for QIVe and $7.52 for QIVcGP visit, hospitalization absenteeism	US Dollar ($), 2021	QIVc versus QIVe was 8.1% (95% CI: 0.1–15.4) in children (6 months–14 years of age) and 11.4% (95% CI: 5.8–16.7) in adolescents and adults (15–64 years of age)^Citation34	3% costs	DSA and PSA	QIVc was cost-effective in the payer perspective (ICER $12,214/QALY in the base case and $2,311.31 in the high egg-adaptation scenario), and dominant in the societal perspective	Compared with QIVe, the use of QIVc in Argentina would be cost-effective and beneficial in children, adolescents, and adults No specific Argentinean WTP threshold; hence, WHO criteria for cost-effectiveness threshold (one GDP per-capita defined a highly cost-effective strategy and three GDP per capita defined a cost-effective intervention)

Note. All studies were sponsored by CSL Seqirus.

aTIV, adjuvanted trivalent influenza vaccine; CE, cost-effectiveness; CEA, cost-effectiveness analysis; CI, confidence interval; DSA, deterministic sensitivity analysis; ER, emergency room; GDP, gross domestic product; GP, general practitioner; ICER, incremental cost-effectiveness ratio; ICU, intensive care unit; N/A, not applicable; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine; rVE, relative vaccine effectiveness; SEIR, susceptible–exposed–infectious–recovered; TIVe, egg-based trivalent influenza vaccine; UK, United Kingdom; VE, vaccine effectiveness; WHO, World Health Organization; WTP, willingness-to-pay.

Table 2. Variation in rVE estimates of QIVc versus QIVe as part of sensitivity/scenario analyses.^{25,27,29–35}

Author, year	rVE of QIVc versus QIVe	Alternative rVE
Ballalai et al., 2021^Citation25	36.2%^†	N/A
Rizzo et al., 2019^Citation27	36.2%^‡	19.3%^‡
Cai et al., 2021^Citation29	36.2%^‡	19.3%^‡
Ruiz-Aragón et al., 2020^Citation30	26.8%^‡	N/A
Nguyen and Roy, 2022^Citation31	15.6%^§	7.6%^║
Nguyen et al., 2021^Citation32	26.8%^†	14–37%^†
Chi et al., 2024^Citation33	8.1%^¶	18.8%^†
Pelton et al., 2024^Citation35	8.1%, children^¶ 11.4%, adults^¶	N/A
Urueña et al., 2022^Citation34	8.1% (95% CI: 0.1–15.4) in children (6 months–14 years of age)^¶ 11.4% (95% CI: 5.8–16.7) in adolescents and adults (15–64 years of age)^¶	18.8% (95% CI: 16.9–20.7) in children^† 26.8% (95% CI: 24.1–29.5) in adolescents^†

^†Data from RWE 2017–2018 season.²⁶

^‡Data from RWE 2017–2018 season.²⁸

^§Estimated from the pooled retrospective studies analysis for the 2017–2018 seasons [unreferenced].

^║Derived from the pooled retrospective studies analysis for the 2018–2019 seasons.^38,39

^¶Data from meta-analysis.³⁴

CI, confidence interval; N/A, not applicable; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine; rVE, relative vaccine effectiveness; RWE, real-world evidence.

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