Cost–effectiveness of vaccinating adults with the 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany

Figures & data

Figure 1. Model structure.

IPD: Invasive pneumococcal disease.

Figure 2. Observed and modeled seroepidemiological changes in the incidence of pneumococcal serotypes causing invasive pneumococcal disease over time from 2005 to 2021 in Germany.

IPD: Invasive pneumococcal disease; PCV: Pneumococcal conjugate vaccine; PPV: Pneumococcal polysaccharide vaccine.

Data taken from [11,25].

Figure 3. Univariate sensitivity analyses.

Attribution factor refers to the proportion of nonbacteremic pneumonia having pneumococcal origin.

^†The maximum value obtained in the sensitivity analysis was €118,382 per quality-adjusted life-year gained, when vaccine effectiveness of 23-valent pneumococcal polysaccharide vaccine against NBPP was assumed to be 0%. The incremental cost–effectiveness ratio was €75,664, €41,789 and €22,848 per quality-adjusted life-year gained, when vaccine effectiveness of 23-valent pneumococcal polysaccharide vaccine against NBPP was assumed to be 5, 15 and 30% in the elderly and at-risk immunocompetent adults, respectively.

HR: Hazard ratio; IPD: Invasive pneumococcal disease; i.s.: Immunosuppressed; NBPP: Nonbacteremic pneumococcal pneumonia; PCV: Pneumococcal conjugate vaccine; VE: Vaccine effectiveness.

Figure 4. Probabilistic sensitivity analysis: cost–effectiveness plane.

ICER: Incremental cost–effectiveness ratio; QALY: Quality-adjusted life year.

Figure 5. Probabilistic sensitivity analysis: cost–effectiveness acceptability curve.

PPV23: 23-valent pneumococcal polysaccharide vaccine; QALY; Quality-adjusted life-year.

Table 1. Clinical parameters.

Parameter	Base-case value (range used in univariate PSA assumptions sensitivity analyses)		Ref. and notes
Split by risk group (%)	AR i.c.: 12.82 (12.81–12.82)		[55]
	AR i.s.: 0.25 (0.2–0.3; as a proportion of the size of nonelderly adult population
Incidence of IPD in 2005 (per 100,000 person-years) by age back in years (%)	16–44: 2.5 (2.0–3.0)	Beta distribution (a/b)	[51]
		16–44: 180.2/7,209,180
	45–64: 8.5 (6.8–10.2)	45–64: 392.3/4,614,596
	65–74: 24.1 (19.3–28.9)	65–74: 263.3/1,092,197
	75+: 10.3 (8.2–12.4)	75+: 194.4/1,886,893
Risk of developing IPD	AR i.c.: 5.494	Log-normal distribution (implied mean/implied SE^†) AR i.c.: 1.660/0.295	[54,55]
	AR i.s.: 35.833 (compared with the nonelderly adult population)	AR i.s.: 3.506/0.382
IPD incidence by serotype in 2005 (%)	PCV7: 45.7		[25]
	PCV13: 76.3
	6A: 3.1
	PPV23: 89.4
	Others: 7.7
Herd protection effect: decrease in incidence of IPD associated with PCV serotypes^‡	Cumulative gamma distribution	Uniform distribution	[9,44,110]
	α: 0.5061
	β: 3.0406	With changes: 50%
	No herd protection; no decrease in PCV13 not PCV7	Without changes: 50%
Serotype replacement effect: increase in incidence of IPD associated with non-PCV serotypes^‡	Cumulative gamma distribution	The same as above	[9,44,110]
	α: 1.4086
	β: 7.6955
	No serotype replacement
Incidence of nonbacteremic pneumonia (per 100,000 person-years) by age back in years (%)	18–19: 33.0	Beta distribution (α/β)	[58]
	20–29: 44.0	18–19: 650/1,969,047
	30–39: 63.0	20–29: 4325/9,825,220
	40–49: 77.0	30–39: 7181/11,390,439
	50–59: 134.0	40–49: 10,463/13,577,200
	60–69: 298.0	50–59: 14,271/10,635,729
	70–79: 739.0	60–69: 29,475/9,861,297
	80–89: 1762.0	70–79: 51,201/6,877,216
	90+: 3581.0	80–79: 55,612/3,100,546
	(All age groups: 370; 600; 870; 1010)	90+: 21,003/565,509
Proportion of nonbacteremic pneumonia having pneumococcal origin (%)	40 (30–50)		[59]
Proportion of meningitis in IPD (%)	8.2		[11]
Proportion of meningitis patients with PMS (%)	52 (22% with hearing loss and 30% with other neurological sequelae)		[62]
Case–fatality rate by age band in years: meningitis (%)	5–49: 21 (17–25)	Beta distribution (a/b)	[56]
		5–49: 5.7/21.6
	50–64: 21 (17–25)	50–64: 9.1/34.2
	65+: 39 (31–47)	65+: 19.2/30.0
Case–fatality rate by age band in years: invasive pneumonia (%)	5–49: 1 (0.8–1.2)	Beta distribution (a/b)	[56]
		5–49: 0.6/59.3
	50–64: 9 (7–11)	50–64: 13.9/140.5
	65+: 20 (16–24)	65+: 136.4/545.6
Relative risk of dying from IPD by serotype (%)	PCV13: 95.3 (91.8–98.4)	Lognormal distribution (implied mean/implied SE^†)	[57]
		PCV13: -4.9%/1.8%
	PPV23 not PCV13/6A: 113.2 (105.4–122.0)	PPV23 not PCV13/6A (compared with PCV13): 17.1%/5.5%
	Not PPV23/6A: 112.7 (102.7–124.0)	Not PPV23/6A (compared with PPV23 not PCV13/6A): -0.5%/1.1%
Case–fatality rate: NBPP (%)	8.6 (6.9–10.3)	Beta distribution (α/β) 87.7/932.0	[59]; 95% CI assumed to be ± 20% of the mean

^†Mean and standard error of implied normal distribution.

^‡As a function of cumulative pneumococcal conjugate vaccine coverage in children.

AR: At-risk adults; i.c.: Immunocompetent; IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PCV: Pneumococcal conjugate vaccine; i.s.: Immunosuppressed; SE: Standard error; PMS: Postmeningitis sequelae; PPV: Pneumococcal polysaccharide vaccine; PSA: Probabilistic sensitivity analysis.

Table 2. Vaccine effectiveness.

Parameter	Base-case value (range used in univariate sensitivity analyses)	PSA assumptions	Ref.
Vaccine effectiveness against IPD (%)	E and AR i.c.: 74 (50–80)	Log-normal distribution (implied mean/implied SE^†) E and AR i.c.: -0.320/0.195	[29,30]
	E and AR i.s.: 35 (24–38)	E and AR i.s.: -1.132/0.405
Vaccine effectiveness against NBPP (%)	E and AR i.c.: 39 (0–64)	Log-normal distribution (implied mean/implied SE^†) E and AR i.c.: -1.025/0.408	[63]
	E and AR i.s.: 0	E and AR i.s.: 0%
Waning function of vaccine effectiveness (proportion of remaining vaccine effectiveness; %)	Year 1: 82 (56–93) Year 2: 78 (41–91) Year 3: 72 (26–89) Year 4: 64 (17–87) Year 5: 54 (10–85) Year 6: 43 (3–83) Year 7: 30 (0–79) Year 8: 15 (0–30) Year 9: 0 (0–20) Year 10: 0 (0–10)	Triangular distribution with the mode being the mean value (minimum/maximum) Year 1: 56/93 Year 2: 41/91 Year 3: 26/89 Year 4: 17/87 Year 5: 10/85 Year 6: 3/83 Year 7: 0/79 Year 8: 0/30 Year 9: 0/20 Year 10: 0/10	[64,65]
Time to receive revaccination	5 years		[66]
Proportion of the vaccinated receiving revaccination	3%, only for those who received the initial vaccination below 60 years of age		[11]

^†Mean and standard error of implied normal distribution.

AR: At-risk adults; E: The elderly; i.c.: Immunocompetent; i.s.: Immunosuppressed; IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PSA: Probabilistic sensitivity analysis; SE: Standard error.

Table 3. Costs and resource use.

Parameter	Base-case value (range used in univariate sensitivity analyses)	PSA assumptions	Ref. and notes
PPV23 vaccine (1-pack price)	TPP: €30.25		[113]
	Societal: €38.45
Administration of PPV23 vaccine	TPP: €6.95 (€5.56–8.34)	Gamma distribution (α/β)	[11]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/0.1
	Societal: €13.95 (€11.16–16.74)	Societal: TPP plus €10
Meningitis	TPP: €11,664 (€9331–13,997)	Gamma distribution (α/β)	[69,114]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/121.4
	Societal: €11,671 (€9337–14,005)	Societal: TPP plus €10
Invasive pneumonia	TPP: €8075 (€6460–9690)	Gamma distribution (α/β)	[69,114]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/84.1
	Societal: €8082 (€6466–9696)	Societal: TPP plus €10
NBPP: inpatient	TPP: €5762 (€4610–6914)	Gamma distribution (α/β)	[69,114]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/96.0
	Societal: €5769 (€4615–6923)	Societal: TPP plus €10
NBPP: outpatient	TPP: €78 (€63–94)	Gamma distribution (α/β)	[69,114]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/0.8
	Societal: €85 (€68–102)	Societal: TPP plus €10
Proportion of NBPP patients hospitalized by age band in years (%)	5–55: 7.8		[69]; 95% CI assumed to be ± 20% of the mean
	56–64: 16.6
	65+: 34.5
PMS: hearing loss (per year)	TPP: €1552 (€1242–1863)	Gamma distribution (α/β)	[70,112]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/16.2
	Societal: €1559 (€1247–1871)	Societal: TPP plus €10
PMS: other neurological sequelae (per year)	TPP: €862 (€690–1035)	Gamma distribution (α/β)	[69,70,112]; 95% CI assumed to be ± 20% of the mean
		TPP: 96.0/9.0
	Societal: €869 (€695–1043)	Societal: TPP plus €10
Cost per day off (societal)	€96^† (€77–115)	Gamma distribution (α/β) 96.0/1.0	[118,119]; 95% CI assumed to be ± 20% of the mean
Productivity loss (societal)	IPD: 16.8 days		[62,117]
	NBPP: 16.8 days
	PMS: 365.25 days
Discount rate (%)	3 (0–5)		[109]

^†Applied until 65 years old.

IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PMS: Postmeningitis sequelae; PPV: Pneumococcal polysaccharide vaccine; PSA: Probabilistic sensitivity analysis; TPP: Third-party payer.

Table 4. Health-related quality of life.

Parameter	Base-case utility, QALYs (range used in univariate sensitivity analyses)	PSA assumptions	Ref.
No pneumococcal diseases (low-risk; by age band in years)	18–54: 0.83	Triangular distribution with the mode being the mean value (minimum/maximum)	[41]
	55–59: 0.81
	60–64: 0.77	18–54: 0.78/0.88
	65–69: 0.76	55–59: 0.76/0.86
	70–74: 0.74	60–64: 0.72/0.82
	75–79: 0.70	65–69: 0.71/0.81
	80–84: 0.63	70–74: 0.69/0.79
	85–89: 0.51	75–79: 0.65/0.75
	90–94: 0.51	80–84: 0.58/0.68
	95–100: 0.51	85–89: 0.46/0.56
No pneumococcal diseases (high-risk; by age band in years)	18–54: 0.72	Triangular distribution with the mode being the mean value (minimum/maximum)	[41]
	55–59: 0.69
	60–64: 0.63	18–54: 0.67/0.77
	65–69: 0.57	55–59: 0.64/0.74
	70–74: 0.54	60–64: 0.58/0.68
	75–79: 0.52	65–69: 0.52/0.62
	80–84: 0.51	70–74: 0.49/0.59
	85–89: 0.51	75–79: 0.47/0.57
	90–94: 0.51	80–84: 0.46/0.56
	95–100: 0.51	85–89: 0.46/0.56
IPD	0.20 (0.16–0.24) for 34 days	Triangular distribution with the mode being the mean value (minimum/maximum)	[41]
	As health-state utility value	0.14/0.25
NBPP	0 (0–0.01)	Triangular distribution with the mode being the mean value (minimum/maximum)
		0/0.01
PMS	Hearing loss: 0.8	Triangular distribution with the mode being the mean value (minimum/maximum)	[72]
	Other neurological sequelae: 0.6	Hearing loss: 0.6/1.0
	As utility multiplier	Other neurological sequelae: 0.45/0.75
Discount rate (%)	3 (0–5)		[109]

IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PMS: Postmeningitis sequelae; PSA: Probabilistic sensitivity analysis; QALY: Quality-adjusted life-year.

Table 5. Results: number of disease cases.

Parameter	PPV23	No vaccination
Size of the target population	833,890
IPD cases	1261	1463
Change (%)	-13.9
NBPP cases	63,236	67,781
Change (%)	-6.7

IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PPV23: 23-valent pneumococcal polysaccharide vaccine.

Table 6. Results: costs from third-party payer perspective (in €1000).

Parameter	PPV23, undisc.	PPV23, disc.	No vaccination, undisc.	No vaccination, disc.	Incremental, undisc.	Incremental, disc.
Vaccine	24,662	24,640	0	0	24,662	24,640
Vaccine administration	5667	5661	0	0	5667	5661
IPD	10,551	6744	12,248	8308	-1697	-1565
NBPP	125,821	76,011	134,712	84,185	-8891	-8174
PMS	1198	526	1405	653	-206	-126
Total	167,899	113,582	148,364	93,145	19,534	20,436

disc.: Discounted; IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PMS: Postmeningitis sequelae; PPV: Pneumococcal polysaccharide vaccine; TPP: Third-party payer; undisc.: Undiscounted.

Table 7. Results: cost from societal perspective (in €1000).

Parameter	PPV23, undisc.	PPV23, disc.	No vaccination, undisc.	No vaccination, disc.	Incremental, undisc.	Incremental, disc.
Vaccine	31,350	31,321	0	0	31,350	31,321
Vaccine administration	11,374	11,364	0	0	11,374	11,364
IPD	11,500	7356	13,345	9056	-1844	-1701
NBPP	130,998	79,415	140,535	88,195	-9537	-8779
Postmeningitis	12,369	6267	14,538	7710	-2168	-1443
Total	197,591	135,722	168,417	104,961	29,174	30,761

disc.: Discounted; IPD: Invasive pneumococcal disease; NBPP: Nonbacteremic pneumococcal pneumonia; PPV: Pneumococcal polysaccharide vaccine; undisc.: Undiscounted.

Table 8. Results: quality-adjusted life years (in 1000).

Parameter	PPV23, undisc.	PPV23, disc.	No vaccination, undisc.	No vaccination, disc.	Incremental, undisc.	Incremental, disc.
Vaccine	10,997	7503	10,993	7499	5	4
Vaccine administration	1	1	1	1	0	0
IPD	37	23	40	26	-3	-3
NBPP	0	0	1	0	0	0
PMS	10,997	7503	10,993	7499	5	4
Total	11,036	7527	11,034	7525	2	1

disc.: Discounted; PMS: Postmeningitis sequelae; PPV: Pneumococcal polysaccharide vaccine; QALY: Quality-adjusted life year; undisc.: Undiscounted.

Table 9. Results: incremental cost–effectiveness ratio.

ICER	Costs per QALY gained
TPP perspective	€17,065
Societal perspective	€25,687

ICER: Incremental cost–effectiveness ratio; QALY: Quality-adjusted life year; TPP: Third-party payer.

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