Cost-effectiveness analysis of adult pneumococcal conjugate vaccines for pneumococcal disease in Japan

Figures & data

Figure 1. Model structure.

IPD: invasive pneumococcal disease; NBP: non-bacteremic pneumococcal pneumonia.

Note: Transitions between risk categories were not included in this study.

Table 1. Base-case model inputs.

Parameters	Values				Source
	50–64 years	65–74 years	75–84 years	85–99 years
Population
Age distribution	126,565 (60–64 high risk only)	1,417,000 (65 only)	–	–	E-stat statistics of Japan [26], Imai et al. [27]
Risk stratifications
Risk stratifications by age group: low/moderate/high	0.0%/0.0%/100.0% (High risk only)	88.1%/10.1%/1.7%			Imai et al. [27]
Allow switching between risk groups	‘No’				Assumption
Vaccine history
Percentage of persons previously vaccinated with					Assumption
PCV13 only	0.0%
PPSV23 only	0.0%
PCV13 + PPSV23	0.0%
Years since vaccination	N/A				Assumption
Disease incidence per 100,000 persons (JMDC [32]and MDV [33] data, 2017–2019)
Incidence of IPD bacteremia: low/moderate/high	1.03/5.89/18.81	3.67/11.01/11.38	4.42/13.26/13.70	4.42/13.26/13.70	NIID [34], e-stat statistics of Japan [26], IASR 2023 [2], Imai et al. [27]
Incidence of IPD meningitis: low/moderate/high	0.09/0.51/1.64	0.32/0.96/0.99	0.38/1.15/1.19	0.38/1.15/1.19	NIID [34], e-stat statistics of Japan [26], IASR 2023 [2], Imai et al. [27]
Incidence of NBP hospitalization: low/moderate/high	140.07/700.33/ 1,428.68	501.53/1,103.37/ 902.76	1,287.96/2,833.51/ 2,318.33	2,237.61/4,922.73/ 4,027.69	JMDC [32], MDV [33], Morimoto et al. [77], Imai et al. [27]
Incidence of NBP outpatient: low/moderate/high	1,061.18/5,305.89/ 10,824.02	2,123.22/4,671.09/ 3,821.80	2,619.56/5,763.03/ 4,715.21	1,075.40/2,365.87/ 1,935.72	JMDC [32], MDV [33], Morimoto et al. [77], Imai et al. [27]
Vaccine serotypes
Vaccine serotype distribution: IPD					IPD information [7]
PCV13 serotypes	29.0%
PCV15 serotypes	35.0%
PCV20 serotypes	61.0%
PPSV23 serotypes	61.7%
Serotype 3	10.7%
Serotype 6A	1.0%
Vaccine serotype distribution: NBP pneumococcal					Assumption (same to IPD)
PCV13 serotypes only	29.0%
PCV15 serotypes only	35.0%
PCV20 serotypes only	61.0%
PPSV23 serotypes only	61.7%
Serotype 3 only	10.7%
Serotype 6A only	1.0%
Proportion of all-cause NBP due to S. pneumoniae	16.5%				Miyazaki et al. [3]
Vaccine coverage
Percentage of persons vaccinated	40.4%	40.4%	N/A		IASR 2018 [9]
Mortality rates per 100 persons
Annual general mortality	0.38	1.23	3.24	11.13	e-stat [26], MHLW [61]
IPD meningitis case fatality	7.14	12.10	12.10	12.10	Chang et al. [62]
IPD bacteremia case fatality	13.82	19.24	19.24	19.24	Chang et al. [62]
NBP hospitalization case fatality	5.52	7.41	10.12	10.12	Miyazaki et al. [3]
Utility
Utility for the general population	0.9280	0.9030	0.8420	0.7890	e-stat [26], Shiroiwa et al. [66]
QALY loss for meningitis	0.1741				Blommaert et al. [67]
QALY loss for bacteremia	0.1741				Blommaert et al. [67]
QALY loss for hospitalized NBP	0.0434				Calculated values*
QALY loss for outpatient NBP	0.0289				Calculated values*
Direct cost
Vaccination cost
PCV20	JPY8,102				Assumption
PCV15	JPY7,200				MHLW [69]
PPSV23	JPY4,735				NHI price revisions [70]
Administration cost	JPY3,250				MHLW medical fee 2022 [72]
IPD meningitis cost	JPY1,636,140	JPY2,178,263	JPY2,178,263	JPY2,178,263	JMDC [32], MDV [33]
IPD bacteremia cost	JPY1,261,855	JPY1,349,205	JPY1,349,205	JPY1,349,205	JMDC [32], MDV [33]
Hospitalized NBP cost	JPY907,530	JPY1,125,977	JPY1,125,977	JPY1,125,977	JMDC [32], MDV [33]
Outpatient NBP cost	JPY33,040	JPY43,646	JPY43,646	JPY43,646	JMDC [32], MDV [33]
Cost related to productivity loss
Employment rate	100%	0%	0%	0%	Assumption
Daily wage: patient	JPY30,402	–	–	–	Wage Structure Basic Statistical Survey [76], assumption
Caregiver utilization rate	0%	100%	100%	100%	Assumption
Daily wage for caregiver	–	JPY30,402	JPY30,402	JPY30,402	Wage Structure Basic Statistical Survey [76], assumption
Days lost because of IPD hospitalization for bacteremia	22	24	24	24	JMDC [32], Konomura et al. [64]
Days lost because of IPD hospitalization for meningitis	32	24	24	24	JMDC [32], Konomura et al. [64]
Days lost because of NBP hospitalization	16	17	17	17	JMDC [32], Konomura et al. [64]
Days lost because of NBP outpatient care	7	7	7	7	Konomura et al. [64]

CDC: US Centers for Disease Control; NHI: National Health Insurance; NIID: National Institute of Infectious Diseases; IASR: Infectious Agents Surveillance Report; IPD: invasive pneumococcal disease; JPY: Japanese yen; MDV: Medical Data Vision Co., Ltd; MHLW: Ministry of Health, Labour and Welfare; NBP: non-bacteremic pneumonia; PCV13: 13-valent pneumococcal vaccine; PCV15: 15-valent pneumococcal vaccine; PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; N/A: Not Applicable.

*Detailed information on the calculations made to estimate those values are described in the supplemental online material.

Table 2. Results of base case in 65-year-old adults and adults at high risk aged 60 to 64 years.

Outcomes	PCV20	PCV15	PPSV23	Differences
				PCV20 vs PPSV23	PCV20 vs PCV15	PCV15 vs PPSV23
Incremental QALY (per person)	14.331	14.331	14.330	0.0015	0.0007	0.0009
Incremental costs (JPY, per person)
Medical care + vaccination	262,316	262,752	262,793	−477	−436	−41
Medical care + productivity loss + vaccination	2,787,585	2,797,827	2,810,098	−22,513	−10,242	−12,271
ICER, JPY/QALY
Societal perspective				Dominant	Dominant	Dominant
Payer perspective				Dominant	Dominant	Dominant
INMB, QALY data
Societal perspective				30,205	13,673	16,532
Payer perspective				8,170	3,867	4,302

ICER: incremental cost-effectiveness ratio; INMB: incremental net monetary benefit; JPY: Japanese yen; PCV15: 15-valent pneumococcal vaccine; PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; QALY: quality-adjusted life year.

When a new strategy (i.e. PCV20) is both more effective and cost saving, it is referred to as an economically ‘dominant’ strategy.

Table 3. Breakdown of health outcomes and costs in base case and scenario analysis 1 in 65-year-old adults and adults at high risk aged 60 to 64 years.

Outcomes	PCV20	PCV15	PPSV23	Differences
				PCV20 vs PPSV23	PCV20 vs PCV15	PCV15 vs PPSV23
Health outcomes, number of cases
IPD
Bacteremia	1,704	1,773	1,821	−117	−69	−47
Meningitis	148	154	158	−10	−6	−4
All-cause NBP
Hospitalized	456,176	457,223	458,637	−2,461	−1,048	−1,413
Requiring outpatient care only	790,825	794,384	799,177	−8,352	−3,559	−4,794
Number of deaths	43,581	43,681	43,807	−226	−100	−126
Costs per population in millions, JPY
Medical care	397,822	399,058	400,659	−2,837	−1,236	−1,601
Productivity loss	3,897,917	3,913,053	3,931,931	−34,013	−15,136	−18,877
Vaccination
Base case	7,079	6,517	4,979	2,100	562	1,537
Scenario 1	6,517	6,517	4,979	1,537	0	1,537

IPD: invasive pneumococcal disease; JPY: Japanese yen; NBP: non-bacterial pneumonia; PCV15: 15-valent pneumococcal vaccine; PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; QALYs: quality-adjusted life years.

Table 4. Scenario analysis (PCV20 vs PPSV23) with different vaccine target population.

Scenario	Vaccine target population	Incremental values			ICER, JPY/QALY gained		INMB, JPY
		QALY	Medical care + productivity losses + vaccination costs (JPY)	Medical care + vaccination costs (JPY)	Societal perspective	Payer perspective	Societal perspective	Payer perspective
	Base case results: reference (65 years and those aged 60–64 years with high risk)	0.0015	−22,513	−477	Dominant	Dominant	30,205	8,170
A	≥65 years and those aged 60–64 years with high risk	0.0015	−26,518	−1,349	Dominant	Dominant	33,967	8,798
B	65 years	0.0015	−21,556	−416	Dominant	Dominant	28,864	7,724
C	65 years and those aged 60–64 years with moderate or high risk	0.0020	−28,346	−897	Dominant	Dominant	38,161	10,712
D	66–84 years	0.0017	−29,983	−1,432	Dominant	Dominant	38,424	9,873

INMB: incremental net monetary benefit; JPY: Japanese yen; PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine.

Table 5. Scenario analysis (PCV20 vs PPSV23) in 65-year-old adults and adults at high risk aged 60 to 64 years.

Scenario	Parameters and scenario settings	Incremental values			ICER, JPY/QALY gained		INMB, JPY
		QALY	Medical care + productivity losses + vaccination costs (JPY)	Medical care + vaccination costs (JPY)	Societal perspective	Payer perspective	Societal perspective	Payer perspective
	Base-case result: reference	0.0015	−22,513	−477	Dominant	Dominant	30,205	8,170
1	Vaccination cost: PCV20 cost equal to PCV13 cost	0.0015	−22,877	−842	Dominant	Dominant	30,569	8,534
2	Vaccine history: Data from Nakashima et al. [36]	0.0015	−22,444	−472	Dominant	Dominant	30,112	8,141
3	Incidence and serotype distribution: Data from COVID-19 era [2,7,26,27,32,34,77]	0.0011	−16,355	−13	Dominant	Dominant	21,993	5,651
4	Proportion of NBP due to S. pneumoniae: 20.0% from Kobayashi et al. [35]	0.0018	−27,110	−847	Dominant	Dominant	36,278	10,015
5	Vaccine coverage: 52.0% from IASR 2023 [2]	0.002	−28,977	−615	Dominant	Dominant	38,878	10,515
6	Vaccine coverage: 20.0%	0.0008	−11,145	−236	Dominant	Dominant	14,953	4,044
7	IPD case fatality: 14.70 per 100 persons from Yanagihara et al. [63]	0.0015	−22,121	−478	Dominant	Dominant	29,686	8,044
8	NBP case fatality: Data from Konomura et al. [64] and Tashiro et al. [65]	0.0015	−21,507	−480	Dominant	Dominant	28,844	7,817
9	Vaccine effectiveness: Increase of 10%	0.0017	−24,759	−655	Dominant	Dominant	33,173	9,069
10	Vaccine effectiveness: Decrease of 10%	0.0014	−20,267	−300	Dominant	Dominant	27,237	7,270
11	Vaccine effectiveness: Increase of 5%	0.0015	−22,329	−467	Dominant	Dominant	29,963	8,101
12	Vaccine effectiveness: Decrease of 5%	0.0013	−19,388	−225	Dominant	Dominant	26,098	6,935
13	PPSV23 effectiveness against NBP: 33.5% from Suzuki et al. [15]	0.0004	−4,261	997	Dominant	2,596,979	6,180	922
14	Herd effects from pediatric PCV20: Data from Mendes 2022 [22]	0.0015	−21,206	−389	Dominant	Dominant	28,491	7,674
15	Herd effects from pediatric PCV20: Data from Japanese epidemiology data [7]	0.0013	−18,388	−160	Dominant	Dominant	24,783	6,555
16	Medication costs: Data from Fukuda et al. [73] and Konomura et al. [64]	0.0015	−21,838	197	Dominant	128,186	29,530	7,495
17	Productivity loss: Exclude vaccine productivity loss	0.0015	−15,168	−477	Dominant	Dominant	22,860	8,170
18	Productivity loss: Apply employment and caregiver utilization rate based on data from public sources [26,74,75]	0.0015	−3,374	−477	Dominant	Dominant	11,066	8,170
19	Productivity loss: 5 days lost because of NBP outpatient care	0.0015	−22,222	−477	Dominant	Dominant	29,914	8,170
20	Productivity loss: 10 days lost because of NBP outpatient care	0.0015	−22,949	−477	Dominant	Dominant	30,641	8,170

IASR: Infectious Agents Surveillance Report; INMB: incremental net monetary benefit; IPD: invasive pneumococcal disease; JMDC: Japan Medical Data Center Inc.; JPY: Japanese yen; MDV: Medical Data Vision Co., Ltd; NBP: non-bacterial pneumonia; OP: Outpatient; PCV13: 13-valent pneumococcal vaccine; PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine.

Figure 2. Deterministic sensitivity analysis results: tornado diagram.

INMB: incremental net monetary benefit; NBP: non-bacterial pneumonia; PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine.

For PCV20 cost, a lower value of 11.13% was applied as we assumed the lowest PCV20 cost would be par to PCV13 cost.

Figure 3. Probabilistic sensitivity analysis results for the cost-effectiveness plane (PCV20 vs PPSV23).

PCV20: 20-valent pneumococcal vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; QALY: quality-adjusted life year

The red line corresponds to the cost-effectiveness threshold of JPY5,000,000 per QALY gained used in this analysis.

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