Cost-effectiveness analysis of COVID-19 booster vaccination with BNT162b2 in Japan

Figures & data

Figure 1. Markov cohort model structure.

In the Markov model component, individuals transition weekly through health states related to COVID-19 protection and infection. If individuals transition into any infection state, they immediately enter. Abbreviations. FBV, first booster vaccination; FPV, full primary vaccination.

Table 1. Base case and the main scenarios explored.

Scenario	Target population	Annual number of vaccination
Base case 1	Age 65 and above + Age 60–64 at high risk	1
Base case 2	Age 65 and above + Age 60–64 at high risk	2
Scenario 1–1	Age 65 and above + Age 12–64 at risk	1
Scenario 1–2	Age 65 and above + Age 12–64 at risk	2
Scenario 2–1	Age 5 and above	1
Scenario 2–2	Age 5 and above	2

See Supplemental Table S1 for the ‘at high risk’ and ‘at risk’ population definitions.

Table 2. Main model parameters for the base case.

Category	Input description	5–11 years	12–17 years	18–29 years	30–59 years	60–64 years	65–74 years	≥75 years	Ref
Vaccine inputs	Booster vaccine coverage (%)	8.7%	45.9%	55.3%	68.6%	86.6%	88.2%	93.8%	[23]
	Vaccine effectiveness (VE) (infection/symptomatic/hospitalization)	60%/70%/80%							[14,22]
	Vaccine-induced duration of protection against infection	6 months							[14]
Infection inputs	Population with infection-induced immunity at the start (%)	30.3%	30.3%	27.1%	22.3%	14.4%	14.4%	14.4%	[27,28]
	Annual attack rate (%)	32.7%	30.5%	27.2%	21.1%	11.1%	9.1%	9.1%	[30]
	Duration of protection from infection-induced immunity	3 months							[14]
Clinical inputs	Hospitalization rate among symptomatic patients (%)	0.8%	0.6%	1.1%	1.3%	2.9%	6.0%	22.8%	[31]
	Among hospitalized patients:
	ICU admission rate (%)	0.1%	0.1%	1.3%	7.2%	7.2%	10.9%	10.9%	[34]
	IMV rate in general ward (%)	0.0%	0.0%	0.4%	4.2%	4.2%	6.8%	6.8%	[34]
	IMV rate in ICU (%)	0.0%	0.0%	0.4%	4.2%	4.2%	6.8%	6.8%	[34]
	Probability of COVID-19 death among infected individuals:
	General ward without IMV (%)	0.0%	0.0%	0.0%	0.1%	0.1%	0.7%	0.7%	[34]
	General ward with IMV (%)	0.0%	0.0%	6.7%	9.1%	9.1%	34.8%	34.8%	[34]
	ICU without IMV (%)	0.0%	0.0%	6.7%	9.1%	9.1%	34.8%	34.8%	[34]
	ICU with IMV (%)	0.0%	0.0%	6.7%	9.1%	9.1%	34.8%	34.8%	[34]
	Outpatient care setting (%)	0.00%	0.00%	0.00%	0.01%	0.08%	0.20%	1.13%	[33]
	Probability of long COVID among infected individuals:
	Asymptomatic patients (%)	0.0%	0.0%	0.0%	0.0%	0.0%	0.0%	0.0%	Assumption
	Patients having received  outpatient care (%)	15.5%	25.3%	34.5%	42.8%	33.1%	32.2%	29.9%	[38]
	Patients having received  inpatient care (%)	35.6%	35.6%	35.6%	46.9%	66.7%	66.7%	66.7%	[39]
Risk inputs	Share of ‘at high risk’ population within age groups	0.1%	0.1%	0.1%	0.4%	0.6%	0.9%	2.3%	[18,19]
	Share of ‘at risk’ population within age groups	1.3%	0.7%	0.6%	1.6%	3.3%	4.8%	6.1%	[19–21]
	Hospitalization risk ratio – ‘at high risk’	1.83							[35]
	Hospitalization risk ratio – ‘at risk’	1.57							[36]
	Mortality risk ratio – ‘at high risk’	1.78							[35]
	Mortality risk ratio- ‘at risk’	1.57							[36]
Vaccine costs	Vaccine acquisition cost per dose for 30 mcg bivalent for individuals 12 years and older (JPY)	13,340							[14,40]
	Vaccine acquisition cost per dose for 10 mcg bivalent for individuals 5 to 11 years (JPY)	8,932							[14,40]
	Vaccine administration cost per dose (JPY)	3,250							[41]
Direct costs in the acute phase	COVID-19 test (JPY)	8,500							[42]
	Number of tests/case (asymptomatic/outpatient/inpatient/ICU)	0/1/3/3							Assumption
	Outpatient visit unit cost (JPY)	28,054							[42]
	Inpatient treatment (JPY)
	General ward  (without/with IMV)	562,650/ 1,449,227	561,632/ 1,449,227	845,761/ 1,449,227	937,469/ 1,449,227	965,039/ 205,148	1,239,964/ 854,644	1,446,865/ 1,986,158	[43]
	ICU (without/with IMV)	3,534,277/ 2,263,806	3,534,277/ 2,263,806	3,534,277/ 3,870,947	1,857,751/ 3,870,947	5,259,124/ 7,413,719	4,079,808/ 6,364,921	3,788,960/ 3,768,221	[43]
Direct costs of sequelae	Long COVID treatment cost (JPY)	107,725							[15,42]
Productivity loss	Asymptomatic (JPY)	36,439							[13,43]
	Symptomatic outpatient (JPY)	60,732							[13,43]
	General ward without IMV (JPY)	255,075							[41,43]
	General ward with IMV (JPY)	485,857							[41,43]
	ICU without IMV (JPY)	485,857							[41,43]
	ICU with IMV (JPY)	485,857							[41,43]
	Patients with long COVID (JPY)	728,786							[46]
QALY outcomes	Utility Decrement (symptoms, general ward, general ward with IMV, ICU, ICU with IMV)	−0.11, −0.17, −0.17, −0.18, −0.18							[48–50]
	Duration (days)
	Symptoms	6							[51]
	General ward  (without/with IMV)	6.0/23.5	4.0/23.5	9.0/23.5	11.0/23.5	16.0/1.0	21.0/48.0	28.0/42.0	[43]
	ICU (without/with IMV)	32.0/16.5	32.0/16.5	32.0/17.0	12.5/17.0	39.5/77.0	40.0/65.0	35.0/36.0	[43]

Refer to the Supplemental Material for further details on the model inputs for the different scenarios.

Abbreviations. COVID-19, coronavirus disease 2019; GP, general physician; ICU, intensive care unit; IMV, invasive mechanical ventilation; JPY, Japanese yen; PASC, post-acute sequelae SARS-CoV-2 infection; QALY, quality-adjusted life year.

Table 3. Results of the cost-effectiveness analysis of booster vaccination with the BNT162b2 vaccine in Japan for the base case over 3 years.

Outcomes	No Vaccination	Annual vaccination	Biannual vaccination	Difference (Annual vs. No vaccination)	%	Difference (Biannual vs. No vaccination)	%
	Base case (Age 65 and above + Age 60–64 at high risk)
Number of symptomatic cases, n	48,544,247	46,628,659	45,623,059	−1,915,588	−3.9%	−2,921,188	−6.0%
Number of total deaths, n	5,902,693	5,879,295	5,867,120	−23,398	−0.4%	−35,573	−0.6%
Number of outpatient cases, n	46,989,653	45,393,130	44,550,805	−1,596,523	−3.4%	−2,438,848	−5.2%
Number of hospitalizations, n	1,554,595	1,235,529	1,072,255	−319,066	−20.5%	−482,340	−31.0%
QALY lost, discounted	4,624,534	4,240,568	4,042,336	−383,965	−8.3%	−582,197	−12.6%
				This value is the difference in QALY lost. Therefore, the incremental QALY is the reversed-sign of this value.
Total medical cost, JPY	7,185,392,203,802	7,858,291,076,096	8,834,103,127,080	672,898,872,293	9.4%	1,648,710,923,277	22.9%
Vaccine-related	0	1,388,130,938,736	2,732,631,287,334	1,388,130,938,736	–	2,732,631,287,334	–
Testing	430,258,155,953	408,994,542,955	397,885,156,142	−21,263,612,998	−4.9%	−32,372,999,812	−7.5%
Adverse event	0	17,645,855	34,737,080	17,645,855	–	34,737,080	–
Inpatient	2,241,244,855,546	1,710,017,210,010	1,438,104,187,429	−531,227,645,537	−23.7%	−803,140,668,117	−35.8%
Outpatient	2,583,497,860,932	2,495,767,555,561	2,449,407,832,555	−87,730,305,371	−3.4%	−134,090,028,377	−5.2%
Long COVID	1,930,391,331,371	1,855,363,182,979	1,816,039,926,539	−75,028,148,392	−3.9%	−114,351,404,831	−5.9%
Productivity loss, JPY	21,683,064,958,283	19,743,705,250,059	18,736,353,819,653	−1,939,359,708,224	−8.9%	−2,946,711,138,630	−13.6%
Overall cost, JPY	28,868,457,162,085	27,601,996,326,154	27,570,456,946,733	−1,266,460,835,931	−4.4%	−1,298,000,215,352	−4.5%
ICER – societal perspective				Dominant		Dominant
ICER – payer perspective, JPY				1,752,499		2,831,878
Net monetary benefit from societal perspective, JPY				3,186,287,995,770		4,208,985,435,324

The reference scenario is no COVID-19 booster vaccination with the BNT162b2 COVID-19 Vaccine. Vaccine-related costs include acquisition and administration. The societal perspective includes productivity losses as well as direct medical costs. The payer perspective includes only direct medical costs.

Abbreviations. ICER, incremental cost-effectiveness ratio; JPY, Japanese yen; QALY, quality-adjusted life year.

Table 4. Results of the cost-effectiveness analysis of booster vaccination with the BNT162b2 vaccine in Japan under two scenarios over 3 years.

Outcomes	No vaccination	Annual vaccination	Biannual vaccination	Difference (Annual vs. No vaccination)	%	Difference (Biannual vs. No vaccination)	%
	Scenario 1 (Age 65 and above + Age 12–64 at risk)
Number of symptomatic cases, n	48,544,172	46,525,917	45,418,026	−2,018,255	−4.2%	−3,126,146	−6.4%
Number of total deaths, n	5,903,358	5,879,744	5,867,443	−23,615	−0.4%	−35,915	−0.6%
Number of outpatient cases, n	46,989,592	45,292,145	44,349,238	−1,697,447	−3.6%	−2,640,354	−5.6%
Number of hospitalizations, n	1,554,580	1,233,772	1,068,788	−320,808	−20.6%	−485,793	−31.2%
QALY lost, discounted	4,631,773	4,236,915	4,028,760	−394,858	−8.5%	−603,013	−13.0%
				This value is the difference in QALY lost. Therefore, the incremental QALY is the reversed-sign of this value.
Total medical cost, JPY	7,186,773,360,914	7,878,640,649,640	8,872,952,984,827	691,867,288,726	9.6%	1,686,179,623,914	23.5%
Vaccine-related	0	1,420,086,667,232	2,795,826,077,613	1,420,086,667,232	–	2,795,826,077,613	–
Testing	430,257,300,974	408,112,056,127	396,124,439,029	−22,145,244,847	−5.1%	−34,132,861,944	−7.9%
Adverse event	0	18,052,075	35,540,410	18,052,075	–	35,540,410	–
Inpatient	2,242,633,226,095	1,709,204,753,361	1,435,304,524,641	−533,428,472,735	−23.8%	−807,328,701,454	−36.0%
Outpatient	2,583,494,548,713	2,490,231,250,523	2,438,355,870,973	−93,263,298,190	−3.6%	−145,138,677,740	−5.6%
Long COVID	1,930,388,285,132	1,850,987,870,323	1,807,306,532,162	−79,400,414,809	−4.1%	−123,081,752,970	−6.4%
Productivity loss, JPY	21,720,972,844,961	19,732,185,841,315	18,680,345,109,773	−1,988,787,003,645	−9.2%	−3,040,627,735,188	−14.0%
Overall cost, JPY	28,907,746,205,874	27,610,826,490,955	27,553,298,094,600	−1,296,919,714,919	−4.5%	−1,354,448,111,274	−4.7%
ICER – societal perspective, JPY				Dominant		Dominant
ICER – payer perspective, JPY				1,752,192		2,796,259
Net monetary benefit from societal perspective, JPY				3,271,210,317,922		4,369,511,056,568
	Scenario 2 (Age 5 and above)
Number of symptomatic cases, n	48,544,499	39,920,686	34,352,514	−8,623,812	−17.8%	−14,191,984	−29.2%
Number of total deaths, n	5,900,475	5,876,457	5,863,850	−24,018	−0.4%	−36,625	−0.6%
Number of outpatient cases, n	46,989,759	38,787,542	33,449,808	−8,202,217	−17.5%	−13,539,951	−28.8%
Number of hospitalizations, n	1,554,739	1,133,144	902,706	−421,595	−27.1%	−652,034	−41.9%
QALY lost, discounted	4,605,430	3,668,385	3,097,546	−937,046	−20.3%	−1,507,884	−32.7%
				This value is the difference in QALY lost. Therefore, the incremental QALY is the reversed-sign of this value.
Total medical cost, JPY	7,181,749,224,491	9,102,975,597,734	11,568,969,159,802	1,921,226,373,243	26.8%	4,387,219,935,311	61.1%
Vaccine-related	0	3,435,300,852,336	6,809,727,032,169	3,435,300,852,336	–	6,809,727,032,169	–
Testing	430,262,621,078	351,566,686,960	301,354,708,945	−78,695,934,119	−18.3%	−128,907,912,133	−30.0%
Adverse event	0	43,687,913	86,601,462	43,687,913	–	86,601,462	–
Inpatient	2,237,578,029,345	1,604,545,368,324	1,266,537,210,950	−633,032,661,021	−28.3%	−971,040,818,395	−43.4%
Outpatient	2,583,503,649,919	2,133,538,305,440	1,840,137,836,564	−449,965,344,479	−17.4%	−743,365,813,355	−28.8%
Long COVID	1,930,404,924,149	1,577,980,696,761	1,351,125,769,713	−352,424,227,388	−18.3%	−579,279,154,436	−30.0%
Productivity loss, JPY	21,581,908,765,147	17,220,791,146,959	14,577,411,148,019	−4,361,117,618,188	−20.2%	−7,004,497,617,127	−32.5%
Overall cost, JPY	28,763,657,989,638	26,323,766,744,693	26,146,380,307,821	−2,439,891,244,945	−8.5%	−2,617,277,681,816	−9.1%
ICER – societal perspective, JPY				Dominant		Dominant
ICER – payer perspective, JPY				2,050,302		2,909,520
Net monetary benefit from societal perspective, JPY				7,125,119,220,929		10,156,699,224,815

The reference scenario is no COVID-19 booster vaccination with the BNT162b2 COVID-19 Vaccine. Vaccine-related costs include acquisition and administration. The societal perspective includes productivity losses as well as direct medical costs. The payer perspective includes only direct medical costs.

Abbreviations. ICER, incremental cost-effectiveness ratio; JPY, Japanese yen; QALY, quality-adjusted life year.

Table 5. Scenario analyses using alternative values for main model inputs.

	Annual vaccination (Base case 1)			Biannual vaccination (Base case 2)
	Incremental QALY, discounted	Incremental total costs, JPY	ICER – societal perspective	Incremental QALY, discounted	Incremental total costs, JPY	ICER – societal perspective
Base case	383,965	−1,266,460,835,931	Dominant	582,197	−1,298,000,215,352	Dominant
Percentage of population with infection-induced immunity at the start of the model horizon
−25% (75% of the base case)	388,563	−1,297,936,743,143	Dominant	586,788	−1,329,421,424,384	Dominant
+25% (125% of the base case)	379,368	−1,234,984,928,719	Dominant	577,606	−1,266,579,006,321	Dominant
Yearly attack rate in susceptible population
Uniformly 30% for all age groups	1,251,250	−7,273,655,159,290	Dominant	1,918,021	−10,569,015,539,456	Dominant
Infection-induced duration of protection against infection
2 months	393,756	−1,335,104,301,926	Dominant	594,347	−1,383,004,117,738	Dominant
4 months	373,828	−1,196,199,595,117	Dominant	570,032	−1,213,709,609,553	Dominant
Efficacy of vaccine against infection and symptomatic cases
50%, 60%	351,617	−1,077,020,423,318	Dominant	533,933	−1,015,413,118,921	Dominant
60%, 60%	351,517	−1,088,169,774,050	Dominant	533,618	−1,030,715,275,204	Dominant
70%, 80%	416,523	−1,457,131,319,426	Dominant	630,664	−1,581,777,737,228	Dominant
Efficacy of vaccine against hospitalization
70%	360,832	−1,072,576,069,039	Dominant	547,669	−1,008,208,106,649	Dominant
90%	407,101	−1,460,362,622,104	Dominant	616,730	−1,587,837,975,812	Dominant
Vaccine-effectiveness duration of protection against infection
5 months	336,616	−938,075,327,063	Dominant	536,679	−981,411,847,922	Dominant
7 months	424,299	−1,546,476,133,510	Dominant	618,045	−1,547,569,460,099	Dominant
Probability of symptomatic infection
Applying highest value for all generations  uniformly (96.9%)	410,539	−1,448,902,225,573	Dominant	622,403	−1,574,454,826,753	Dominant
Applying lowest value for all generations  uniformly (89.7%)	379,982	−1,242,412,654,323	Dominant	576,070	−1,260,928,939,630	Dominant
Hospitalization rate among symptomatic patients
−25% (75% of the base case)	341,186	−906,639,901,909	Dominant	517,502	−752,809,522,509	Dominant
+25% (125% of the base case)	426,704	−1,625,944,354,746	Dominant	646,835	−1,842,714,092,041	Dominant
Hospitalization cost (general ward without IMV)
25%ile value	383,965	−1,098,900,131,119	Dominant	582,197	−1,044,518,542,894	Dominant
75%ile value	383,965	−1,522,206,547,083	Dominant	582,197	−1,684,861,559,305	Dominant

Abbreviations. ICER, incremental cost-effectiveness ratio; IMV, invasive mechanical ventilation; JPY, Japanese yen, QALY, quality-adjusted life year.

Figure 2. Deterministic sensitivity analyses for annual and biannual groups: Tornado diagrams for incremental net monetary benefit – societal perspective.

Color of the bar indicates whether the parameter is at its lower or upper bound. 647 parameters were tested, and this figure includes only the 10 most impactful parameters. Abbreviations. JPY, Japanese yen; Q1, first quartile; Q3, third quartile.

Figure 3. Probabilistic sensitivity analysis: cost-effectiveness acceptability curve for societal perspective.

The results were calculated by individual level. Abbreviations. JPY, Japanese yen.

Figure 4. Probabilistic sensitivity analysis: cost-effectiveness plane for societal perspective.

The results were calculated by individual level. Abbreviations. JPY, Japanese yen, QALY, quality-adjusted life year.

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