Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium

Figures & data

Figure 1.  Health states used in the Markov model, and permitted transitions between states.

Table 1.  Model inputs: epidemiology, vaccine characteristics and utilities.

Model input	Base case analysis			Deterministic sensitivity analysis
	HZ	PHN		HZ	PHN
Epidemiology
HZ incidence (per 1,000 people) and PHN proportion per HZ case (%)	Belgian Health Authorities27,28	GPRD (1 month)29*	GPRD (3 months)	Opstelten et al.7
Age 50–54 years	4.0	10.3 (14.1)	7.6	3.6	3.9 (5.3)**
Age 55–59 years	3.5	13.7 (18.8)	9.8	5.8	6.5 (8.9)
Age 60–64 years	5.6	15.7 (21.5)	11.0	5.8	6.5 (8.9)
Age 65–69 years	5.8	18.7 (26.5)	13.1	6.5	10.7 (14.7)
Age 70–74 years	7.1	22.5 (30.4)	15.2	6.5	10.7 (14.5)
Age 75–79 years	10.2	26.6 (36.0)	18.0	9.1	18.0 (24.3)
Age 80–84 years	11.6	28.9 (39.0)	20.6	9.1	18.0 (24.3)
Age 85–89 years	13.9	25.9 (35.0)†	18.5	9.1	18.0 (24.3)
Age 90–94 years	11.2			9.1	18.0 (24.3)
Age ≥ 95 years	18.2			9.1	18.0 (24.3)
Mean duration (months)	SPS data19
Age ≤ 69 years	1.0	8.3
Age ≥ 70 years	1.0	10.9
Annual HZ mortality (%)	GPRD29 and expert opinion			Edmunds et al.40
Age 50–54 years	0	0		0.0009	–
Age 55–59 years	0	0		0.0009	–
Age 60–64 years	0	0		0.0027	–
Age 65–69 years	0	0		0.0027	–
Age 70–74 years	0	0		0.0035	–
Age 75–79 years	0	0		0.0092	–
Age 80–84 years	0	0		0.0487	–
Age 85–89 years	0	0		0.2018	–
Age 90–94 years	0	0		0.2018	–
Age ≥ 95 years	0	0		0.2018	–
Pain split (%)	SPS data19			GPRD29
Age ≤ 69 years
No pain	27	–		65
Mild pain	41	42		24	48
Moderate pain	18	9		4	42
Severe pain	14	49		8	10
Age ≥ 70 years
No pain	26	–		45
Mild pain	32	17		41	37
Moderate pain	23	16		5	54
Severe pain	19	67		9	9
Incidence of recurrent HZ (%)	Cunningham et al.2
Age 50–54 years	0.09	–‡
Age 55–59 years	0.10	–
Age 60–64 years	0.12	–
Age 65–69 years	0.14	–
Age 70–74 years	0.18	–
Age 75–79 years	0.23	–
Age 80–84 years	0.30	–
Age 85–89 years	0.42	–
Age 90–94 years	0.60	–
Age 95–99 years	0.87	–
Age 100 years	1.1	–
Vaccine characteristics
Efficacy: reduction in number of cases (%)	SPS data19
Age 50–69 years	63.9	65.7
Age ≥ 70 years	37.6	66.8
Efficacy: reduction in PHN duration (months)
Age 60–69 years	–	−2.2 (26.5)
Age ≥ 70 years	–	−3.3 (30.3)
Vaccine cost, including copayments (€)	141.18			100.38–160.38
Quality of life
Age-specific utilities (males/females)	EuroQoL group34,35
Age 50–54 years	0.798/0.801	0.798/0.801
Age 55–59 years	0.798/0.801	0.798/0.801
Age 60–64 years	0.773/0.800	0.773/0.800
Age 65–69 years	0.773/0.800	0.773/0.800
Age 70–74 years	0.714/0.733	0.714/0.733
Age 75–79 years	0.714/0.733	0.714/0.733
Age ≥ 80 years	0.730/0.686	0.730/0.686
Utility decrements	Oster et al.18			SPS data19§	Bala et al.42§
No pain	0.00	–		0.14
Mild pain	0.31	0.31		0.23	0.27
Moderate pain	0.42	0.42		0.32	0.40
Severe pain	0.75	0.75		0.45	0.53

GPRD, General Practice Research Database.

*PHN proportion is shown as the incidences derived from Gauthier et al.25 using the 1-month definition of PHN, and values adjusted by applying the pain split observed in the SPS to ensure that the GPRD data reflect all HZ cases with pain.

**Data from the study by Opstelten et al.6, adjusted in the same way.

†Age ≥ 85 years.

‡It was assumed that the proportion of patients with PHN after recurrent HZ would be the same as that following a first episode.

§Same increments apply to both HZ and PHN.

Table 2.  Model inputs: healthcare resource use (2007 prices). Monthly costs.

Perspective	No pain		Mild pain			Moderate pain		Severe pain
	TPP	Healthcare/ societal	TPP		Healthcare/ societal	TPP	Healthcare/ societal	TPP	Healthcare/ societal
HZ ambulatory management costs (€)
Primary and secondary ambulatory care	22.72	28.71	25.17		32.20	45.45	61.09	78.93	59.72
Medications	31.99	43.74	39.70		57.54	66.11	98.72	79.93	129.26
Non-pharmacological   treatments	0.00	0.00	5.76		6.40	36.55	37.59	89.34	90.99
Diagnostic tests	2.63	2.68	2.57		2.65	6.39	6.73	19.55	21.04
Total HZ costs	57.34	75.13	73.20		98.79	154.49	204.12	265.75	301.01
HZ hospitalization costs
Hospitalisation rate (%)	0.11		0.22			8.33		15.56
Mean length of hospital stay (days)	3		3			4.67		6.29
Mean unit cost of hospitalisation (societal perspective (€)	317.24
Mean HZ total cost (€)	0.97	1.06	1.97	2.11		113.99	123.37	288.66	310.19
PHN* ambulatory management costs (€)
Primary and secondary ambulatory care			52.22	67.87		53.29	120.15	68.40	94.18
Medications			6.93	22.63		27.32	61.67	56.20	130.28
Non-pharmacological   treatments			10.64	11.17		43.22	43.97	120.99	124.10
Diagnostic tests			8.14	8.55		12.17	12.87	25.37	27.34
Total PHN costs			77.93	110.22		136.00	238.66	270.96	375.90
PHN hospitalisation costs
Hospitalisation rate (%)			0.42			2.33		11.75
Mean length of hospital stay (days)			4.5			6.75		6.44
Mean unit cost of hospitalisation (societal perspective (€)			317.24
Mean total PHN costs (€)			5.49	5.95		46.57	49.96	227.90	240.22

TPP, third party payer.

*1-month definition.

Table 3.  Costs of lost productivity due to HZ and PHN.

	Pain level	Days lost from work	Proportion of patients (%)	Cost of lost productivity by age group (€)
				50–54 years	55–59 years	60–64 years	65–69 years
HZ	None	6	4.38	36.77	22.56	7.45	2.67
	Mild	6.33	12.50	110.90	68.05	22.48	8.04
	Moderate	6.33	39.38	496.42	304.61	100.62	35.99
	Severe	11.07	78.75	1,221.35	749.43	247.56	88.55
PHN	Mild	6.17	9.17	8.67	5.28	1.72	0.61
	Moderate	11.4	33.33	58.29	35.52	11.58	4.13
	Severe	19.18	52.58	154.71	94.28	30.73	10.95

Table 4.  Base-case analysis: lifetime cost-effectiveness in individuals aged 60 years and older.

	ICER (€)
	TPP	Healthcare	Societal
Cost per QALY	6,799	7,168	7,137
Cost per HZ case avoided	1,308	1,379	1,373
Cost per PHN case avoided (1-month definition)	3,936	4,149	4,131
Cost per PHN case avoided (3-month definition)	3,842	4,050	4,033

Table 5.  Subgroup analyses: lifetime cost-effectiveness by age group.

Subgroup	≥50 years	≥65 years	60–64 years	65–69 years	60–69 years
HZ cases prevented	78,522	26,185	13,296	11,792	25,088
PHN cases prevented
1-month definition	23,303	9421	3700	3476	7176
3-month definition	23,943	9783	3659	3448	7107
QALYs gained	12,396	5687	1908	1906	3814
ICERs
Cost per QALY (€)	6,614*	€7,173*	€5,686*	€5,404*	€5,545*
	€6,966†	€7,575†	€5,953†	€5,647†	€5,800†
	€6,812‡	€7,566‡	€5,858‡	€5,620‡	€5,739‡
Cost per HZ case avoided (€)	€1,044*	€1,558*	€816*	€873*	€843*
	€1,100†	€1,645†	€855†	€913†	€882†
	€1,075‡	€1,643‡	€841‡	€908‡	€873‡
Cost per PHN case avoided (€)
1-month definition	€3,518*	€4,330	€2,932*	€2,963*	€2,947*
	€3,706†	€4,573†	€3,070†	€3,096†	€3,083†
	€3,624‡	€4,567‡	€3,021‡	€3,082‡	€3,050‡
3-month definition	€3,490*	€4,170*	€2,965*	€2,987*	€2,976*
	€3,676†	€4,403†	€3,105†	€3,122†	€3,113†
	€3,595‡	€4,398‡	€3,055‡	€3,107‡	€3,080‡
NNV to avoid one HZ case	9	14	8	8	8
NNV to prevent one PHN case
1-month definition	32	39	27	28	28
3-month definition	32	37	28	28	28

*,†,‡Third party payer, healthcare and societal perspective, respectively.

Figure 2.  Tornado diagrams showing the outcome of deterministic sensitivity analyses from third party payer (a), healthcare (b) and societal (c) perspectives. The vertical line represents the base-case incremental cost-effectiveness ratio (ICER; cost per quality-adjusted life year [QALY]), as shown in Table 4. The bars represent the change in ICER resulting from alterations in the variable shown on the left of the figure. GPRD, General Practice Research Database; HZ, herpes zoster; PHN, post-herpetic neuralgia; SPS, Shingles Prevention Study.

Figure 3.  Scatter plots showing the outcome of probabilistic sensitivity analyses using Monte Carlo simulations. Results are presented as costs per quality-adjusted life year (QALY) from third party payer (a), healthcare (b) and societal (c) perspectives.

Figure 4.  Cost-effectiveness acceptability curve. The dotted line indicates the unofficial Belgian threshold for cost-effectiveness of €30,000.

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