Cost-effectiveness of the cell-based quadrivalent versus the standard egg-based quadrivalent influenza vaccine in Germany

Figures & data

Table 1. Vaccine effectiveness for Settings A and B in the 4Flu model.

	Setting A (e.g. g-adaptation occurs in 100% of years)					Setting B (e.g. g-adaptation occurs in 55% of years)
Age group (years)	VE against A(H3N2)			VE against other strains		VE against A(H3N2)			VE against other strains
	QIVc	QIVe		QIVc*	QIVe* (%)	QIVc	QIVe		QIVc*	QIVe* (%)
		Normal year (%)	Egg-adapted change year (%)				Normal year (%)	Egg-adapted change year (%)
0–8	NA	44.95	33.00	NA	69	NA	38.65	28.38	NA	69
9–17	44.95%	44.95	33.00	69%	69	38.65%	38.65	28.38	69%	69
18–64	44.95%	44.95	33.00	73%	73	38.65%	38.65	28.38	73%	73
65+	44.95%	44.95	33.00	62%	62	38.65%	38.65	28.38	62%	62

Abbreviations. NA, not applicable; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine; VE, vaccine effectiveness.

*Values apply to all simulations.

A mean VE (33%) of QIVe against A(H3N2) was averaged over all years (years with and without egg-adaptation) and is based on the rVE and on previous findings reported by Belongia et al.²⁶. For the other influenza strains and lineages, the same VE was used for QIVc and QIVe in all years sourced by papers of Jefferson et al.^28–30.

Table 2. Annualized disutility due to symptomatic influenza (calculated*).

Age group (years)	Disutility influenza (no antiviral treatment)	Disutility influenza (antiviral treatment)
0–4	−0.006	−0.005
5–17	−0.006	−0.005
18–49	−0.007	−0.006
50–64	−0.007	−0.006
65–69	−0.009	−0.008
70–74	−0.009	−0.008
75–79	−0.009	−0.008
80–84	−0.009	−0.008
85+	−0.009	−0.008

*Average utility decrements (365.25 days) during an influenza episode were multiplied by duration of influenza symptoms to obtain the disutility associated with clinical influenza cases.

The annual disutility and duration of influenza were taken from Dolk et al.²⁰. The event disutilities reported here were calculated with the formula annual disutility*duration/365.25.

Table 3. Disutility due to complications (calculated*).

	Bronchitis	Pneumonia	URTI	Myocarditis	MI	Renal	CNS	Stroke	Otitis media	GI bleeding
Disutility hospitalized patients	−0.0090	−0.0116	−0.0073	−0.0085	−0.3800	−0.0120	−0.0088	−0.3800	−0.0036	−0.0053
∟Disutility hospitalization	−0.0070	−0.0096	−0.0062	−0.0074	−0.3800	−0.0105	−0.0067	−0.3800	−0.0034	−0.0044
∟Disutility of three extra ambulatory days	−0.0021	−0.0021	−0.0010	−0.0011	NA	−0.0014	−0.0022	NA	−0.0001	−0.0010
Disutility ambulatory patients	−0.0046	−0.0063	−0.0021	−0.0025	−0.1980	−0.0049	−0.0046	−0.2870	−0.0001	−0.0014

Abbreviations. CNS, central nervous system; GI, gastrointestinal bleeding; MI, myocardial infarction; NA, not applicable as we assumed one-off disutility for stroke and MI; URTI, unspecified upper tract respiratory infection.

*Average utility decrements (365.25 days) during an influenza episode were multiplied by duration of influenza symptoms to obtain the disutility associated with clinical influenza cases.

The disutilities of stroke and MI were taken from Ara et al.³⁵ and are event disutilities. The disutility and duration of the other complications were derived from Dolk et al.²⁰. The values reported were calculated using the disutility*duration/365.25²⁰.

Table 4. The annual clinical outcomes for Settings A and B in the cohort size of 100,000 individuals.

	Setting A (e.g. g-adaptation occurs in 100% of years)				Setting B (e.g. g-adaptation occurs in 55% of years)
	QIVe	QIVe + QIVc	Increment	% Incremental	QIVe	QIVe + QIVc	Increment	% Incremental
Number of symptomatic influenza cases (Total)	151,610	147,556	−4,054	−3	154,369	152,277	−2,092	−1
└normal risk	123,756	120,706	−3,051	−2	125,959	124,392	−1,567	−1
└high risk	27,854	26,851	−1,003	−4	28,410	27,885	−525	−2
Number of GP visits for symptomatic influenza cases (Total)	45,389	44,150	−1,239	−3	46,214	45,574	−640	−1
└normal risk	34,949	34,087	−863	−2	35,566	35,123	−443	−1
└high risk	10,440	10,064	−376	−4	10,648	10,451	−197	−2
Number of complications (Total)	16,111	15,691	−419	−3	16,403	16,186	−216	−1
└normal risk	12,274	11,991	−283	−2	12,490	12,345	−145	−1
└high risk	3,836	3,700	−136	−4	3,913	3,841	−71	−2
Number of hospitalized complications (Total)	1,574	1,523	−51	−3	1,605	1,579	−26	−2
└normal risk	987	959	−28	−3	1,005	991	−15	−1
└high risk	587	565	−23	−4	600	588	−12	−2
Number of deaths (Total)	66	64	−2	−3	68	66	−1	−1
└normal risk	31	30	−1	−3	32	31	−1	−3
└high risk	35	34	−1	−3	36	35	−1	−3

Abbreviations. GP, general practitioner; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine.

Table 5. The annual health economic outcomes for Settings A and B in the cohort size of 100,000 individuals.

	Setting A (e.g. g-adaptation occurs in 100% of years)				Setting B (e.g. g-adaptation occurs in 55% of years)
	Total QALY (total)	Costs (grand total)	ICER (total)	NMB (total)	Total QALY (total)	Costs (grand total)	ICER (total)	NMB (total)
Total population (normal risk + high risk)
QIVe	1,353,698	198,246,715 €	Dominant	5,512,075 €	1,353,674	201,473,808 €	Dominant	2,697,974 €
QIVe + QIVc*	1,353,738	193,918,002 €			1,353,695	199,393,087 €
Incremental	39	−4,328,713 €			21	−2,080,721 €
Normal risk population
QIVe	1,063,509	169,995,098 €	Dominant	4,384,296 €	1,063,492	172,788,358 €	Dominant	2,161,388 €
QIVe + QIVc*	1,063,534	166,369,318 €			1,063,505	171,020,225 €
Incremental	25	−3,625,781 €			13	−1,768,132 €
High risk population
QIVe	290,190	28,251,617 €	Dominant	1,127,778 €	290,182	28,685,450 €	Dominant	536,586 €
QIVe + QIVc*	290,204	27,548,685 €			290,189	28,372,861 €
Incremental	14	−702,932 €			7	−312,588 €

Abbreviations. GP, general practitioner; ICER, incremental cost-effectiveness ratio; NMB, net monetary benefit; €, Euros; QALYs, quality-adjusted life-years; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine.

*QIVc vaccination was provided in population aged 9 years + and QIVe vaccination was provided in population aged < 9 years.

Table 6. Payer perspective scenario analysis annual health economic outcomes for Settings A (egg-adaptation occurs in 100% of all years) and B (egg-adaptation occurs in 55% of all years) in the cohort size of 100,000 individuals.

	Scenario: Setting A (payer perspective^)				Scenario: Setting B (payer perspective^)
	Total QALY (Total)	Costs (Grand total)	ICER (Total)	NMB (Total)	Total QALY (Total)	Costs (Grand total)	ICER (Total)	NMB (Total)
Total population (normal risk + high risk)
QIVe	1,353,698	15,669,610 €	2,285 €	1,093,209 €	1,353,674	15,801,809 €	8,984 €	432,411 €
QIVe + QIVc*	1,353,738	15,759,763 €			1,353,695	15,986,652 €
Incremental	39	90,152 €			21	184,842 €
Normal risk population
QIVe	1,063,509	10,777,386 €	2,227 €	702,209 €	1,063,492	10,868,217 €	8,823 €	277,597 €
QIVe + QIVc*	1,063,534	10,833,692 €			1,063,505	10,983,876 €
Incremental	25	56,306 €			13	115,659 €
High risk population
QIVe	290,190	4,892,225 €	2,389 €	391,000 €	290,182	4,933,592 €	9,266 €	154,814 €
QIVe + QIVc*	290,204	4,926,071 €			290,189	5,002,775 €
Incremental	14	33,846 €			7	69,183 €

Abbreviations. GP, general practitioner; ICER, incremental cost-effectiveness ratio; NMB, net monetary benefit; QALY, quality-adjusted life-year; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine; rVE, relative vaccine effectiveness; €, Euros.

*QIVc vaccination was provided in population aged 9 years + and QIVe vaccination was provided in population aged < 9 years.

^From a payer perspective, instead of rVE of 36.2%, a scenario with rVE of 19.3% (for both Settings A and B) was considered based on Constantina Boikos et al. publication²⁵.

Table 7. Scenario analysis annual health economic outcomes for Settings A (egg-adaptation occurs in 100% of all years) and B (egg-adaptation occurs in 55% of all years) in the entire German population.

Setting			Setting A (e.g. egg-adaptation occurs in 100% of years)			Setting B (e.g. egg-adaptation occurs in 55% of years)
			Incremental QALYs	Incremental Costs, €	ICER (€/QALY gained)	Incremental QALYs	Incremental Costs, €	ICER (€/QALY gained)
Base case		Societal and 36.2%	1,628	−178,606,268	Dominant	849	−85,852,259	Dominant
Scenario 1	rVE	Societal and 19.3%	895	−93,264,396	Dominant	427	−36,017,877	Dominant
Scenario 2	Perspective	Payer and 36.2%	1,628	3,719,764	2,285	849	7,626,753	8,984
Scenario 3	Perspective and rVE	Payer and 19.3%	895	7,340,493	8,199	427	9,758,197	22,845

Abbreviations. ICER, incremental cost-effectiveness ratio; QALYs, quality-adjusted life-years; rVE, relative vaccine effectiveness.

Figure 1. Deterministic sensitivity analysis: impact of the 10 key drivers on the NMB (Settings A [egg-adaptation occurs in 100% of all years] and B [egg-adaptation occurs in 55% of all years], societal perspective, 100,000 individuals). (a) Impact of the 10 key drivers on the NMB for Setting A. (b) Impact of the 10 key drivers on the NMB for Setting B. Abbreviations. aVE, absolute vaccine effectiveness; NMB, net monetary benefit; OSWA, one-way sensitivity analyses; rVE, relative vaccine effectiveness. Setting A: egg-adaptation occurs in 100% of all years. Setting B: egg-adaptation occurs in 55% of all years. % of death and % of hospitalizations are due to the following complications: bronchitis, pneumonia, unspecified upper tract respiratory infection, myocarditis, myocardial infarction, renal, central nervous system, stroke, otitis media, gastrointestinal bleedings where the base case values were changed with ±10%; disutilities due to influenza symptoms, baseline utilities, and disutilities due to influenza hospitalization changed with ±10%.

Figure 2. Scatter plot and cost-effectiveness acceptability curve for PSA with 1,000 iterations for Setting A (egg-adaptation occurs in 100% of years), societal perspective. (a) Scatter plot of PSA for Setting A. (b) Cost-effectiveness acceptability curve (CEAC) for Setting A. Abbreviations. CEAC, cost-effectiveness acceptability curve; PSA, probabilistic sensitivity analyses; QALYs, quality-adjusted life-years; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine; €, Euros. Setting A: egg-adaptation occurs in 100% of all years.

Figure 3. Scatter plot and cost-effectiveness acceptability curve for PSA with 1,000 iterations for Setting B (egg-adaptation occurs in 55% of years), societal perspective. (a) Scatter plot of PSA for Setting B. (b) Cost-effectiveness acceptability curve (CEAC) for Setting B. Abbreviations. CEAC, cost-effectiveness acceptability curve; PSA, probabilistic sensitivity analyses; QALYs, quality-adjusted life-years; QIVc, cell-based quadrivalent influenza vaccine; QIVe, egg-based quadrivalent influenza vaccine; €, Euros. Setting B: egg-adaptation occurs in 55% of all years.

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