Public health impact and economic value of booster vaccination with Pfizer-BioNTech COVID-19 vaccine, bivalent (Original and Omicron BA.4/BA.5) in the United States

Figures & data

Figure 1. Economic model structure combining (A) Markov cohort model and (B) decision tree component used in both the cost-effectiveness and the budget impact analyses. 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 (B) the decision tree component for sorting. Green circles indicate decision points, with probabilities informed by the level of protection against COVID-19 in the particular infected state from which an individual arrives. Red triangles indicate decision tree end points, from which participants re-enter the Markov model component. Abbreviations. ICU, intensive care unit; SBV, second booster vaccination.

Table 1. Main model parameters for the base case.

Category	Input description	5–11 years	12–17 years		18–29 years			30–49 years		50–64 years	65–74 years	75+ years	References
Infection inputs	Population with infection-induced immunity at the start (%)	44.2	45.6		36.5			36.5		28.8	19.1	19.1	^26
	Annual attack rate (%)	25.2	28.5		29.4			31.0		28.6	28.8	37.7	^23
	Duration of protection from infection-induced immunity	3 months											^25
Vaccine inputs	Booster vaccine coverage (%)	8.3	17.6		21.4			26.6		35.3	44.0	46.6	^3^,^5
	Vaccine-induced duration of protection against infection	6 months											^29^,^30^,^32–36
	Vaccine effectiveness (VE) (infection/symptomatic/hospitalization)	60% / 70% / 80%
Clinical inputs	Hospitalization rate among symptomatic patients (%)	0.1	0.3		1.1	1.3				2.5	4.4	9.0	^44
	Among hospitalized patients:
	ICU admission rate (%)	29.7	29.7		11.9	17.6				24.3	26.9	21.3	^47
	IMV rate in general ward (%)	0.9	0.9		1.4	3.1				5.9	7.8	7.4
	IMV rate in ICU (%)	27.6	27.6		39.1	48.8				60.5	63.6	53.2
	Probability of COVID-19 death among infected individuals:
	General ward without IMV (%)	0.0	0.1		0.0	0.1				1.1	4.3	12.9
	General ward with IMV (%)	0.0	0.0		15.1	23.1				40.2	53.5	66.3
	ICU without ventilation (%)	0.0	0.0		0.6	0.8				3.6	10.4	25.4
	ICU with ventilation (%)	9.1	9.1		20.0	32.3				48.2	60.4	69.7
	Outpatient care setting (%)	0.0	0.0		0.0	0.0				0.2	0.5	1.8	^48
	Asymptomatic patients (%)	0.0	0.0		0.0	0.0				0.0	0.0	0.0	Assumption
	Probability of long COVID among infected individuals:
	Asymptomatic patients (%)	4.2	20.8		20.8	20.8				20.8	26.9	26.9	^49^,^54
	Patients having received outpatient care (%)	4.2	20.8		20.8	20.8				20.8	26.9	26.9	^49^,^54
	Patients having received inpatient care (%)	10.2	49.2		49.2	49.2				49.2	63.6	63.6	^49^,^54
Vaccine costs	Vaccine administration cost per dose (USD)	28.4											^59
	Vaccine acquisition cost per dose for 10 mcg bivalent for individuals 5 to 11 years (USD)	77											^60
	Vaccine acquisition cost per dose for 30 mcg bivalent for individuals 12 years and older (USD)	115											^60
Direct costs in the acute phase	COVID test (USD)	43.6											^59
	Number of tests/case (outpatient/inpatient/ICU)	2 / 3/ 3											^57
	GP visit number/ cost (USD)	2 / 229											^13^,^57
	OTC pain medication (USD)	205											^57
	In-patient treatment (USD)
	General ward (without/with IMV)	14,325 / 41,769											^47
	ICU (without/with IMV)	25,688 / 78,245
Direct costs of sequelae	Long COVID treatment cost (USD)	5,969											^13^,^47^,^55
Indirect costs	Asymptomatic (USD)	0	1	18			27		24		7	2	^64–68
	Symptomatic outpatient (USD)	0	74	922			1,351		1,180		365	122
	General ward without IMV (USD)	0	119	1,484			2,175		1,900		588	196
	General ward with IMV (USD)	0	1,354	16,865			24,725		21,597		6,684	2,228
	ICU without IMV (USD)	0	145	1,806			2,648		2,313		716	239
	ICU with IMV (USD)	0	1,354	16,865			24,725		21,597		6,684	2,228
	Patients with Long COVID (USD)	0	666	8,294			12,160		10,621		3,287	1,096
QALY outcomes	Utility Decrement (symptoms, GW, GW IMV, ICU, ICU IMV)	−0.093, −0.3, −0.6, −0.5, −0.6, 0.034											^69–74
	Duration (days) (symptoms, GW, GW IMV, ICU, ICU IMV)	28, 4, 9, 8, 15, 365											^47^,^70

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

Abbreviations. COVID-19, coronavirus disease 2019; ICU, intensive care unit; IMV, invasive mechanical ventilation; GP, general physician; OTC, over the counter; QALY, quality-adjusted life year; USD, United States dollar; VE, vaccine effectiveness; GW, general ward.

Table 2. Projected COVID-19 health and economic outcomes in the absence of COVID-19 vaccination in individuals ≥5 years old in the US under three burden of disease scenarios over one year.

Outcomes	Low	Base case	High
Symptomatic cases, n	38,444,718	51,636,594	70,279,345
Deaths, n	91,287	381,647	1,128,515
Outpatient cases, n	38,099,528	50,164,125	66,742,405
Hospitalizations, n	345,191	1,472,469	3,536,940
General ward without IMV	272,603	1,076,952	2,388,050
General ward with IMV	13,044	70,437	198,524
ICU without IMV	32,902	142,078	306,638
ICU with IMV	26,641	183,003	643,728
QALY lost, discounted	1,408,054	3,726,701	10,007,493
LY lost, discounted	961,432	3,632,115	10,560,212
Direct costs, USD	$85,385,041,552	$163,591,156,731	$320,700,098,148
Vaccine-related	$0	$0	$0
Inpatient	$5,903,701,333	$36,338,181,341	$120,895,657,496
Outpatient	$23,850,304,226	$33,258,814,545	$46,986,653,116
Testing	$3,352,379,427	$4,566,910,645	$9,346,748,916
Long COVID	$52,278,656,566	$89,427,250,198	$143,471,038,620
Indirect costs, USD	$133,755,889,763	$199,979,502,224	$321,330,814,086
Total costs, USD	$219,140,931,315	$363,570,658,954	$642,030,912,234

Note. Vaccine-related costs include acquisition, administration and adverse events management.

Abbreviations. ICU, intensive care unit; IMV, invasive mechanical ventilation; LY, life year; QALY, quality-adjusted life year; USD, United States dollar.

Table 3. Results of the cost-effectiveness analysis of booster vaccination with the Pfizer-BioNTech COVID-19 vaccine, bivalent (Original and Omicron BA.4/BA.5) in individuals ≥5 years old in the US under three burden of disease scenarios over one year.

Outcomes	Low	Base case	High
Averted symptomatic cases, n	−3,551,543	−3,717,921	−3,780,114
Averted deaths, n	−13,214	−44,792	−99,044
Averted outpatient cases, n	−3,503,226	−3,555,582	−3,488,114
Averted hospitalizations, n	−48,317	−162,339	−292,000
General ward without IMV	−37,771	−117,439	−195,009
General ward with IMV	−1,977	−8,302	−17,322
ICU without IMV	−4,685	−15,780	−25,180
ICU with IMV	−3,883	−20,819	−54,490
QALY saved, discounted	−159,279	−373,236	−782,991
LY saved, discounted	−129,153	−404,635	−888,238
Direct cost savings, USD billions	$4,205,400,521	−$2,428,806,475	−$11,803,441,719
Vaccine-related	$11,353,818,257	$9,740,303,035	$8,134,993,843
Inpatient	−$838,267,489	−$4,063,361,251	−$10,112,847,012
Outpatient	−$2,193,019,707	−$2,357,351,040	−$2,455,632,536
Testing	−$309,694,540	−$331,280,673	−$507,170,116
Long COVID	−$3,860,210,202	−$5,440,148,746	−$6,882,373,190
Indirect cost savings, USD billions	−$10,569,238,666	−$13,107,055,487	−$17,575,200,366
Total cost savings, USD billions	−$6,363,838,145	−$15,535,861,961	−$29,378,642,085
ICER – payer perspective	$26,237	Dominant	Dominant
ICER – societal perspective	Dominant	Dominant	Dominant
ROI	2.13	4.67	10.07
Net monetary benefit	$14,354,190,603	$34,197,669,630	$68,528,177,908

Notes: The reference scenario is no COVID-19 booster vaccination with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent. The payer perspective includes only direct medical costs. The societal perspective includes indirect costs as well as direct medical costs. Vaccine-related costs include acquisition, administration and adverse events management.

Abbreviations. ICU, intensive care unit; IMV, invasive mechanical ventilation; LY, life year; QALY, quality-adjusted life year; USD, United States dollar; ROI, return on investment.

Table 4. Base case results of the budget impact analysis of booster vaccination with the Pfizer-BioNTech COVID-19 vaccine, bivalent (Original and Omicron BA.4/BA.5) in the US for a 1-million-member plan over one year.

Cost (USD)	No Vaccination with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)	Vaccination with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)	Difference
A. Base case budget impact results for a 1-million-member plan in individuals ≥5 years old.
Vaccine-related costs	$0	$34,645,683	$34,645,683
Total direct costs	$603,148,823	$538,277,085	−$64,871,737
Inpatient	$134,178,121	$114,394,783	−$19,783,338
Outpatient	$122,713,285	$109,915,735	−$12,797,550
Testing	$17,009,025	$15,199,046	−$1,809,979
Long COVID	$329,248,392	$298,767,521	−$30,480,871
Net direct costs	$603,148,823	$572,922,769	−$30,226,054
Net cost PMPY – payer perspective	$603	$572	−$30
Sensitivity analyses with indirect costs	$1,182,619,244	$1,100,841,989	−$81,777,255
Net cost PMPY – societal perspective	$1,182	$1,100	−$82
B. Base case budget impact results for a 1-million-member plan in individuals ≥12 years old.
Vaccine-related costs	$0	$34,371,649	$34,371,649
Total direct costs	$597,053,743	$532,342,353	−$64,711,390
Inpatient	$134,178,121	$114,394,783	−$19,783,338
Outpatient	$119,126,652	$106,428,802	−$12,697,849
Testing	$16,536,104	$14,739,275	−$1,796,829
Long COVID	$327,212,866	$296,779,492	−$30,433,374
Net direct costs	$597,053,743	$566,714,001	−$30,339,742
Net cost PMPY – payer perspective	$597	$566	−$30
Sensitivity analyses with indirect costs	$1,176,524,164	$1,094,633,221	−$81,890,943
Net cost PMPY – societal perspective	$1,176	$1,094	−$82

Note: The payer perspective includes only direct medical costs. The societal perspective includes indirect costs as well as direct medical costs.

Abbreviation. PMPY, Per Member Per Year.

Table 5. Base case population-level outcomes in individuals ≥5 years old in additional sensitivity analysis using alternative values for main model inputs.

Variables	Symptomatic cases averted		Deaths averted		Hospitalizations averted		Direct care cost savings (USD billion)		Indirect cost savings (USD billion)
	N (% difference)		N (% difference)		N (% difference)		N (% difference)		N (% difference)
Base case	3,717,921	N/A	44,792	N/A	162,339	N/A	$2.4	N/A	$13.1	N/A
Duration of Infection-induced immunity
2 months	4,184,526	12.5%	48,606	8.5%	176,420	8.7%	$3.9	62.1%	$15.0	14.3%
4 months	3,316,049	−10.8%	41,577	−7.2%	150,303	−7.4%	$1.1	−53.3%	$11.5	−12.3%
Vaccine duration of protection against infection
7 months	4,225,178	13.6%	50,126	11.9%	182,395	12.4%	$4.1	67.8%	$15.0	14.2%
5 months	3,123,832	−16.0%	38,503	−14.0%	138,823	−14.5%	$0.5	−79.5%	$10.9	−16.6%
Vaccine acquisition cost for ≥12 years old
− 30% ($80.5 / dose)	3,717,921	N/A	44,792	N/A	162,339	0%	$4.8	96.4%	$13.1	0%
+ 30% ($149.5 / dose)	3,717,921	N/A	44,792	N/A	162,339	0%	$0.1	−96.4%	$13.1	0%
GP visit unit cost
− 30% ($160)	3,717,921	N/A	44,792	N/A	162,339	0%	$1.3	−48.5%	$13.1	0%
+ 30% ($298)	3,717,921	N/A	44,792	N/A	162,339	0%	$3.6	48.5%	$13.1	0%
Initial VE against infection and VE symptomatic disease
50%, 60%	2,932,279	−21.1%	40,966	−8.5%	162,162	−0.1%	$0.5	−79.9%	$10.6	−18.9%
60%, 60%	2,918,697	−21.5%	40,919	−8.6%	162,377	0.0%	$1.80	−25.0%	$12.10	−7.6%
70%, 80%	4,522,791	21.6%	48,722	8.8%	162,515	0.1%	$4.40	83.3%	$15.60	19.1%
Initial VE against hospitalization
70%	3,718,507	0.02%	40,182	−10.3%	133,729	−17.6%	$1.60	−33.3%	$12.50	−4.6%
90%	3,717,335	−0.02%	49,402	10.3%	190,949	17.6%	$3.10	29.2%	$13.6	3.8%
Long COVID care
Lower re-admission: 4%^11	3,717,921	N/A	44,792	N/A	162,339	0%	$2.0	−16.1%	$13.1	0%
Higher re-admission: 15%^11	3,717,921	N/A	44,792	N/A	162,339	0%	$3.5	43.0%	$13.1	0%
Care management costs
Vaccine Administration costs ($16.9 per dose)^56	3,717,921	N/A	44,792	N/A	162,339	0%	$3.3	32.5%	$13.1	0%
Vaccine Administration costs ($40 per dose)^56	3,717,921	N/A	44,792	N/A	162,339	0%	$1.6	−32.5%	$13.1	0%

Note: The reference scenario is no vaccination with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

Abbreviations. GP, general physicians; VE, vaccine effectiveness.

Figure 2. Deterministic sensitivity analysis: Tornado diagram for incremental cost – societal perspective in individuals ≥5 years old. Color of the bar indicates whether the parameter is at its lower or upper bound. Over 400 parameters were tested and this figure includes only the 20 most impactful parameters.

Figure 3. Probabilistic sensitivity analysis: cost-effectiveness plane for societal perspective in individuals ≥5 years old.

Figure 4. Probabilistic sensitivity analysis: cost-effectiveness acceptability curve for societal perspective in individuals ≥5 years old.

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Data availability statement

Aggregate data generated or analyzed during this study are available upon request.