Cost-effectiveness analysis of 20-valent pneumococcal conjugate vaccine for routine pediatric vaccination programs in Japan

Figures & data

Figure 1. Model schematic.

AOM, acute otitis media; IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine.

Table 1. Model input values for base scenario analysis.

Parameters	Age group (years)
	0–<1	1–<2	2–<3	3–<4	4–<5	5–17	18–34	35–49	50–64	65–<100	Sources
Population size (1,000 person)	830	836	871	915	938	13,665	21,508	25,256	24,468	36,128	[33]
Annual disease incidence (100,000 person-years)^a
IPD	11.04	10.22	10.22	10.22	10.22	0.54	0.34	0.85	1.99	5.46	[33,34]
Hospitalized pneumonia^b	2,353.7	2,353.7	909.6	909.6	909.6	141.1	75.1	75.1	219.0	1,225.6	[35,36]
Non-hospitalized pneumonia^b	7,808.2	7,808.2	8,694.4	8,694.4	8,694.4	2,231.1	1,009.0	1,009.0	1,659.2	2,395.7	[35,36]
AOM with myringotomy	1,832.1	1,832.1	866.0	866.0	866.0	―	―	―	―	―	[35]
AOM without myringotomy	27,071.7	27,071.7	27,666.9	27,666.9	27,666.9	―	―	―	―	―	[35]
Breakdown of IPD cases (%)
Meningitis^ｃ	6	6	6	6	6	6	6	6	6	8	[37]
Case fatality rates (%)
Meningitis^ｄ	3.7	3.7	3.7	3.7	3.7	3.7	7.1	7.1	7.1	12.1	[2,38,39]
Bacteremia^e	4.0	4.0	4.0	4.0	4.0	4.0	13.8	13.8	13.8	19.2	[38,40]
Hospitalized pneumonia^f	0.08	0.08	0.08	0.08	0.08	0.17	0.26	1.33	2.58	16.87	[33,35,36,41,42]
Probability of sequalae (%)
Deafness due to meningitis^g	2.2	2.2	2.2	2.2	2.2	2.2	4.1	7.1	6.1	6.6	[43,44]
Disability due to meningitis^g	16.5	16.5	16.5	16.5	16.5	16.5	12.6	22.0	19.0	20.4
Vaccine uptake, PCV13/15/20%)
Primary doses	97.9	—	—	—	—	—	—	—	—	—	[32]
Booster dose	97.1	—	—	—	—	—	—	—	—	—
Serotype distribution (%)^a
PCV13	3.1	3.1	3.1	3.1	3.1	3.1	29.2	29.2	29.2	29.2	[5]
PCV15	10.3	10.3	10.3	10.3	10.3	10.3	35.0	35.0	35.0	35.0
PCV20	37.7	37.7	37.7	37.7	37.7	37.7	61.1	61.1	61.1	61.1
Utility decrements
Meningitis	0.023	0.023	0.023	0.023	0.023	0.023	0.130	0.130	0.130	0.130	[45–47]
Bacteremia	0.008	0.008	0.008	0.008	0.008	0.008	0.130	0.130	0.130	0.130	[45–47]
Hospitalized pneumonia	0.006	0.006	0.006	0.006	0.006	0.006	0.130	0.130	0.130	0.130	[45–47]
Non-hospitalized pneumonia	0.004	0.004	0.004	0.004	0.004	0.004	0.045	0.045	0.045	0.045	[45–47]
AOM (with/without myringotomy)	0.005	0.005	0.005	0.005	0.005	0.005	―	―	―	―	[45–47]
Utility multiplier for lifetime events (sequalae)
Deafness due to meningitis	0.73										[48]
Disability due to meningitis	0.60										[49]
Vaccine costs (JPY, per dose)
PCV13/15/20 (Base scenario A)^h	11,600/11,600/12,502										[50,51] Assumption
PCV13/15/20 (Base scenario B)^h	11,600/11,600/11,600
Medical cost per episode (JPY)
Meningitis	916,735	916,735	453,080	453,080	453,080	901,920	1,224,450	1,224,450	1,731,160	2,178,263	[35,52]
Bacteremia	706,080	706,080	720,200	720,200	720,200	1,243,500	925,585	925,585	1,280,460	1,349,205
Hospitalized pneumonia	338,150	338,150	322,330	322,330	322,330	439,440	695,635	695,635	932,215	1,125,977
Non-hospitalized pneumonia	28,310	28,310	24,630	24,630	24,630	22,140	28,070	28,070	33,490	43,646
AOM with myringotomy	90,220	90,220	54,930	54,930	54,930	―	―	―	―	―
AOM without myringotomy	24,260	24,260	18,760	18,760	18,760	―	―	―	―	―
Lifetime medical cost per episode of sequalae (JPY)^i
Deafness	762,705										[53]
Disability	4,054,885	4,054,885	3,678,360	3,678,360	3,678,360	3,678,360	3,678,360	3,678,360	3,678,360	3,678,360
Productivity losses of guardians due to vaccination (JPY, per dose)^j
PCV13/15/20	9,405										[35,54] Assumption
Productivity loss costs due to disease (JPY, per episode)^k
Meningitis	235,118	235,118	235,118	235,118	235,118	357,380	432,618	432,618	583,094	583,094	[35,54]
Bacteremia	225,714	225,714	225,714	225,714	225,714	413,808	319,761	319,761	413,808	432,618
Hospitalized pneumonia	169,285	169,285	169,285	169,285	169,285	188,095	244,523	244,523	319,761	376,189
Non-hospitalized pneumonia	75,238	75,238	75,238	75,238	75,238	75,238	75,238	75,238	75,238	75,238
AOM with myringotomy	56,428	56,428	56,428	56,428	56,428	―	―	―	―	―
AOM without myringotomy	56,428	56,428	56,428	56,428	56,428	―	―	―	―	―

AOM, acute otitis media; IPD, invasive pneumococcal disease; JPY, Japanese yen; PCV, pneumococcal conjugate vaccine.

^aAverage between 2017 and 2019.

^bFor incidence at ages 65 years and older, we multiplied the incidence at ages 50–64 years from the JMDC analysis by the relative risk at ages 65–74, 75–84, and 85 years and older estimated by Morimoto et al. 2015 [36]. We then adjusted for the Japanese population estimates.

^cValues for ages 5–64 years were assumed to be the same as those under 5 years. The proportion of cases with meningitis among IPD was sourced from the NIID [37] and the remaining cases were assumed to be with bacteremia.

^dValues for ages 0–17 years were calculated by summing data from Shinjoh et al. 2017 and Shinjoh et al. 2020 [2,39]; values for ages 18 years and older were from Chang et al. 2022 [38].

^eValues for ages 0–17 years were from Nakano et al. 2020 [40]; for ages 18 and older, they were from Chang et al. 2022 [38].

^fThe number of deaths due to pneumonia in Vital Statistics was divided by the number of hospitalized pneumonia patients. The number of hospitalized pneumonia patients was calculated using Japanese population estimates based on the incidence of hospitalized pneumonia patients. The mortality rate for outpatient pneumonia was assumed to be 0.

^gValues for ages 0–17 years were from Iwata et al. 2021 [43] and for ages 18 years and older were from Iwata et al. 2023 [44].

^hPCV20 acquisition costs were assumed to be JPY 8,102 or JPY 7,200 in base scenarios A and B, respectively. Administration cost was assumed as JPY 4,400.

ⁱThe annual costs cited in Suaya et al. 2015 [53] were converted to the April 2022 reimbursement rate level for cost adjustment and multiplied by 10 years of analysis period.

^jProductivity losses due to vaccination were calculated by multiplying the daily wage by half a day.

^kFor meningitis, bacteremia, and inpatient pneumonia, the median number of days of hospitalization from the JMDC analysis plus three days was multiplied by the average daily wage from the Basic Wage Structure Survey. For non-hospitalized pneumonia and AOM, the median number of treatment days based on expert opinion was assumed to be four and three days, respectively, and multiplied by the average daily wage.

Table 2. Results of base scenario A.

Outcomes	PCV20	PCV15	PCV13	Incremental values
				PCV20 vs. PCV13	PCV20 vs. PCV15	PCV15 vs. PCV13
QALYs
per population	3,210,738,526	3,210,497,665	3,210,443,926	294,599	240,861	53,738
per person^a	405.200	405.170	405.164	0.036	0.030	0.007
Total costs from societal perspective (JPY)
per population	11,666,475,234,068	11,947,246,389,681	12,019,112,550,588	−352,637,316,521	−280,771,155,614	−71,866,160,907
per person^a	1,472,327	1,507,763	1,516,833	−44,506	−35,436	−9,070
Total costs from payer perspective (JPY)
per population	7,213,910,248,984	7,354,471,703,093	7,392,810,804,820	−178,900,555,837	−140,561,454,109	−38,339,101,727
per person^a	910,406	928,147	932,986	−22,579	−17,740	−4,839
ICER (JPY/QALY gained)
Societal perspective	—	—	—	Dominant	Dominant	Dominant
Payer perspective	—	—	—	Dominant	Dominant	Dominant

ICER, incremental cost-effectiveness ratio; JPY, Japanese yen; PCV, pneumococcal conjugate vaccine; QALY, quality-adjusted life-year.

^aPer person outcomes were calculated by dividing the per population outcomes by the number of the vaccinated infants receiving each primary vaccine dose (7,923,835, 7,923,823 and 7,923,819 for PCV20, PCV15 and PCV13, respectively).

Figure 2. Cost-effectiveness plane for three vaccination programs (per population) in base scenario A.

a. Societal perspective.

b. Payer perspective.

¥/JPY , Japanese yen; PCV, pneumococcal conjugate vaccine; QALY, quality-adjusted life-year.

Table 3. Detailed incremental values in base scenarios and scenario 1 (indirect effects excluded) – societal perspective.

Outcomes	Base scenario			Scenario 1 (indirect effects excluded)
	PCV20 vs. PCV13	PCV20 vs. PCV15	PCV15 vs. PCV13	PCV20 vs. PCV13	PCV20 vs. PCV15	PCV15 vs. PCV13
Health outcomes (number of cases)
Meningitis	−677	−552	−125	−58	−45	−12
Bacteremia	−8,621	−7,028	−1,593	−899	−713	−187
Hospitalized pneumonia	−229,346	−185,302	−44,045	−52,136	−41,296	−10,840
Non-hospitalized pneumonia	−1,279,141	−1,034,497	−244,643	−70,373	−55,741	−14,632
AOM with myringotomy	−25,839	−20,466	−5,372	−12,778	−10,121	−2,657
AOM without myringotomy	−558,316	−442,232	−116,085	−272,217	−215,618	−56,599
Total deaths due to disease	−13,656	−11,179	−2,477	−82	−65	−17
Medical costs (JPY)
Vaccination
Base scenario A	24,977,315,323	24,977,123,058	192,265	24,976,979,489	24,976,852,013	127,476
Base scenario B	924,705	732,439	192,265	613,100	485,624	127,476
Treatment costs (JPY)
Meningitis	−1,136,710,455	−929,564,703	−207,145,752	−33,895,368	−26,847,845	−7,047,524
Bacteremia	−9,363,397,653	−7,646,256,752	−1,717,140,901	−568,594,004	−450,372,060	−118,221,944
Hospitalized pneumonia	−147,237,918,649	−119,789,780,649	−27,448,138,000	−15,830,838,322	−12,539,290,512	−3,291,547,810
Non-hospitalized pneumonia	−33,482,593,752	−27,136,062,764	−6,346,530,988	−1,622,634,439	−1,285,256,676	−337,377,763
AOM with myringotomy	−1,743,438,426	−1,380,943,089	−362,495,337	−876,292,667	−694,093,817	−182,198,850
AOM without myringotomy	−10,445,976,888	−8,274,054,421	−2,171,922,467	−5,145,518,314	−4,075,662,770	−1,069,855,544
Lifetime cost of sequalae	−467,835,336	−381,914,789	−85,920,547	−33,642,762	−26,647,765	−6,994,998
Productivity losses (JPY)	−173,736,760,684	−140,209,701,504	−33,527,059,180	−27,463,455,263	−21,753,257,555	−5,710,197,708

AOM, acute otitis media; JPY, Japanese yen; PCV, pneumococcal conjugate vaccine.

Table 4. Results of base scenario B and scenario 1.

Outcomes	PCV20	PCV15	PCV13	Incremental values
				PCV20 vs. PCV13	PCV20 vs. PCV15	PCV15 vs. PCV13
Base scenario B
QALYs	3,210,738,526	3,210,497,665	3,210,443,926	294,599	240,861	53,738
Total costs (JPY)
Societal perspective	11,641,498,843,449	11,947,246,389,681	12,019,112,550,588	−377,613,707,139	−305,747,546,232	−71,866,160,907
Payer perspective	7,188,933,858,365	7,354,471,703,093	7,392,810,804,820	−203,876,946,455	−165,537,844,728	−38,339,101,727
ICER (JPY/QALY gained)
Societal perspective	—	—	—	Dominant	Dominant	Dominant
Payer perspective	—	—	—	Dominant	Dominant	Dominant
Scenario 1: Indirect effects excluded from base scenario A
QALYs	3,210,451,322	3,210,445,464	3,210,443,926	7,396	5,858	1,538
Total costs (JPY)
Societal perspective	11,992,514,658,938	12,008,389,235,925	12,019,112,550,588	−26,597,891,651	−15,874,576,987	−10,723,314,664
Payer perspective	7,393,676,368,433	7,387,797,687,864	7,392,810,804,820	865,563,612	5,878,680,568	−5,013,116,956
ICER (JPY/QALY gained)
Societal perspective	—	—	—	Dominant	Dominant	Dominant
Payer perspective	—	—	—	117,032	1,003,501	Dominant
Scenario 1: Indirect effects excluded from base scenario B
QALYs	3,210,451,322	3,210,445,464	3,210,443,926	7,396	5,858	1,538
Total costs (JPY)
Societal perspective	11,967,538,292,549	12,008,389,235,925	12,019,112,550,588	−51,574,258,039	−40,850,943,376	−10,723,314,664
Payer perspective	7,368,700,002,044	7,387,797,687,864	7,392,810,804,820	−24,110,802,776	−19,097,685,820	−5,013,116,956
ICER (JPY/QALY gained)
Societal perspective	—	—	—	Dominant	Dominant	Dominant
Payer perspective	—	—	—	Dominant	Dominant	Dominant

ICER, incremental cost-effectiveness ratio; JPY, Japanese yen; PCV, pneumococcal conjugate vaccine; QALY, quality-adjusted life-year.

Table 5. Results of scenario analyses for PCV20 versus PCV13.

Parameters and scenario settings	Incremental values			ICER (JPY/QALY gained)		INMB (JPY)
	QALY	Medical costs	Productivity losses	Societal perspective	Payer perspective	Societal perspective	Payer perspective
Base scenario A (reference)	294,599	−178,900,555,837	−173,736,760,684	Dominant	Dominant	1,825,632,747,748	1,651,895,987,065
Include indirect effects
IPD only (Scenario 2)	34,490	−9,419,971,640	−30,606,501,299	Dominant	Dominant	212,478,242,615	39,219,325,398
Incidence and serotype distribution
Apply data from COVID-19 era (Scenario 3)	195,912	−96,201,062,013	−88,097,606,136	Dominant	Dominant	1,163,859,863,975	1,075,762,257,839
Vaccine uptake
100% (Scenario 4)	294,715	−178,828,592,831	−174,367,366,497	Dominant	Dominant	1,826,770,078,509	1,652,402,712,012
95% (Scenario 5)	294,498	−179,146,167,027	−173,205,931,586	Dominant	Dominant	1,824,841,676,896	1,651,635,745,310
Direct effect for those aged < 1
Full direct effect (Scenario 6)	295,011	−180,712,260,018	−175,495,791,792	Dominant	Dominant	1,831,262,332,809	1,655,766,541,017
Productivity loss costs
Apply employment rate and proportion of patients 65+ who require help (Scenario 7)	294,599	−178,900,555,837	−118,899,993,775	Dominant	Dominant	1,770,795,980,840	1,651,895,987,065
Include probability of sequelae
Not considered (Scenario 8)	293,791	−178,432,720,501	−173,736,760,684	Dominant	Dominant	1,821,126,895,854	1,647,390,135,171
QALY decrement
Apply utility multipliers (Scenario 9)	278,585	−178,900,555,837	−173,736,760,684	Dominant	Dominant	1,745,561,405,568	1,571,824,644,885
CFRs for meningitis, bacteremia
Data from Kakenhi [68] (Scenario 10)	292,179	−178,901,855,019	−173,739,055,881	Dominant	Dominant	1,813,536,511,767	1,639,797,455,886
Incidence and cost data of AOM
Data from Yamanaka et al. 2009 [69](Scenario 11)	299,277	−225,297,113,154	−226,535,213,606	Dominant	Dominant	1,948,219,544,927	1,721,684,331,322

AOM, acute otitis media; CFRs, case fatality rates; COVID-19, coronavirus disease 2019; ICER, incremental cost-effectiveness ratio; INMB, incremental net monetary benefit; IPD, invasive pneumococcal disease; JPY, Japanese yen; PCV, pneumococcal conjugate vaccine; QALY, quality-adjusted life-year.

Figure 3. Tornado plot for PCV20 vs. PCV13 (INMB).

AOM, acute otitis media; CI, confidence interval; INMB, incremental net monetary benefit; IPD, invasive pneumococcal disease; IQR, interquartile range; JPY, Japanese yen; PCV, pneumococcal conjugate vaccine.

Figure 4. PSA scatterplot for PCV20 vs. PCV13.

¥/JPY, Japanese yen; PCV, pneumococcal conjugate vaccine; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life-year.

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Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article or its supplemental materials.