Cost-effectiveness of using a 20-valent pneumococcal conjugate vaccine to directly protect adults in England at elevated risk of pneumococcal disease

Figures & data

Figure 1. Model schematic.

Table 1. Base case model input values.

				Age and Risk Profile
				18–49 Years			50–64 Years			65–74 Years				75–84 Years				85-99 Years
				Moderate	High		Moderate	High		Low	Moderate	High		Low	Moderate	High		Low	Moderate	High
No. of adults (in thousands)				1,254.6	449.5		1,784.1	1,315.7		3,392.3	1,220.8	963.3		1,970.8	1,005.5	818.2		626.0	456.0	379.1
Annual disease incidence (per 100,000)
	Bacteremia			18.7	42.0		17.6	48.9		4.8	18.8	62.3		8.1	21.9	94.7		15.0	40.5	175.4
	Meningitis			2.1	4.7		1.7	4.8		0.3	1.1	3.6		0.3	0.7	3.0		0.1	0.3	1.5
	All-cause hospitalized CAP			247.7	452.4		700.6	1,279.3		769.7	2,301.4	4,202.5		939.7	2,809.7	5,130.8		1,498.7	4,481.2	8,183.1
Annual mortality/case-fatality (per 100)
	General population			0.1	0.2		0.6	0.8		1.1	1.7	2.3		3.0	4.5	6.0		9.6	14.4	19.2
	Bacteremia			6.0	7.2		12.8	15.4		14.0	17.5	21.0		22.0	27.5	33.0		32.3	40.3	48.4
	Meningitis			6.0	7.2		12.8	15.4		14.0	17.5	21.0		22.0	27.5	33.0		32.3	40.3	48.4
	All-cause hospitalized CAP			3.4	4.1		6.7	8.0		7.9	9.9	11.8		10.3	12.9	15.5		14.5	18.1	21.7
General population health-state utilities				0.7745	0.7346		0.7234	0.6852		0.9283	0.7308	0.7082		0.8921	0.6799	0.6607		0.8191	0.6038	0.5643
Vaccine coverage
	PCV20*			43.4%	37.5%		43.4%	37.5%		42.9%	79.0%	83.7%		73.3%	89.6%	95.5%		77.9%	85.9%	85.7%
	PPV23**			43.4%	37.5%		43.4%	37.5%		42.9%	79.0%	83.7%		73.3%	89.6%	95.5%		77.9%	85.9%	85.7%
VE PCV vs. VT-IPD
	Year 1			81.5%	65.2%		79.2%	63.3%		75.0%	75.0%	60.0%		75.0%	75.0%	60.0%		75.0%	75.0%	60.0%
	Year 5			81.5%	65.2%		79.2%	63.3%		75.0%	75.0%	60.0%		75.0%	75.0%	60.0%		75.0%	75.0%	60.0%
	Year 10			63.1%	50.5%		61.2%	49.0%		58.0%	58.0%	46.4%		58.0%	58.0%	46.4%		58.0%	58.0%	46.4%
	Year 15			37.2%	29.8%		36.2%	28.9%		34.3%	34.3%	27.4%		34.3%	34.3%	27.4%		34.3%	34.3%	27.4%
	Year 16+			0.0%	0.0%		0.0%	0.0%		0.0%	0.0%	0.0%		0.0%	0.0%	0.0%		0.0%	0.0%	0.0%
VE PCV vs. VT-CAP
	Year 1			55.6%	44.5%		51.3%	41.1%		45.0%	45.0%	36.0%		45.0%	45.0%	36.0%		45.0%	45.0%	36.0%
	Year 5			55.6%	44.5%		51.3%	41.1%		45.0%	45.0%	36.0%		45.0%	45.0%	36.0%		45.0%	45.0%	36.0%
	Year 10			43.0%	34.4%		39.7%	31.8%		34.8%	34.8%	27.9%		34.8%	34.8%	27.9%		34.8%	34.8%	27.9%
	Year 15			25.4%	20.3%		23.5%	18.8%		20.6%	20.6%	16.4%		20.6%	20.6%	16.4%		20.6%	20.6%	16.4%
	Year 16+			0.0%	0.0%		0.0%	0.0%		0.0%	0.0%	0.0%		0.0%	0.0%	0.0%		0.0%	0.0%	0.0%
VE PPV23 vs. VT-IPD
	Year 1			32.7%	17.0%		32.4%	16.9%		55.9%	31.1%	16.2%		50.8%	28.2%	14.7%		37.6%	20.9%	10.9%
	Year 5			24.9%	13.0%		24.7%	12.8%		42.6%	23.7%	12.3%		38.7%	21.5%	11.2%		28.7%	15.9%	8.3%
	Year 10+			0.0%	0.0%		0.0%	0.0%		0.0%	0.0%	0.0%		0.0%	0.0%	0.0%		0.0%	0.0%	0.0%

*Vaccine uptake of PCVs was the same in sequential strategies involving PCV20→PPV23 and PCV15→PPV23; in such strategies, 100% of persons who received PCV and were alive in year 2 were assumed to receive PPV23

**Vaccine uptake was the same in the PPV23 strategy with revaccination; 100% of persons who received the initial dose of PPV23 were assumed to receive the second dose assuming they were alive in year 6

Figure 2. Cost-effectiveness plane for alternative vaccination strategies among moderate- and high-risk adults aged 18–64 years and all adults aged 65–99 years in England (N = 15,635,909).

Table 2. Results of base case analyses of alternative vaccination strategies among moderate- and high-risk adults aged 18–64 years and all adults aged 65–99 years in England (N = 15,635,909).

A. Clinical and Economic Outcomes
		PPV23 (1 dose)	PCV20	PCV20→PPV23	PPV23+PPV23	PCV15→PPV23
Clinical Outcomes
	No. of cases
	IPD	117,807	110,018	109,709	117,031	113,644
	All-cause hospitalized CAP	7,483,128	7,343,082	7,343,116	7,483,223	7,384,442
	No. of deaths
	IPD	37,612	35,191	35,106	37,377	36,247
	All-cause hospitalized CAP	1,122,633	1,102,854	1,102,860	1,122,651	1,108,621
	Life-years (discounted)	179,787,906	179,906,103	179,906,580	179,788,893	179,867,258
	Quality-adjusted life-years (discounted)	132,546,963	132,638,338	132,638,681	132,547,656	132,608,379
Economic Outcomes (in millions)
	Medical care	£19,971.1	£19,432.8	£19,431.6	£19,968.7	£19,604.2
	Vaccination	£256.2	£634.9	£871.4	£424.0	£812.2
	Medical + vaccination	£20,227.3	£20,067.7	£20,303.0	£20,392.7	£20,416.4
B. Incremental Cost-Effectiveness
Strategy		Cost (in millions)	QALYs	Incremental Cost (in millions)	Incremental QALYs	ICER
PCV20		£20,067.7	132,638,338	–	–	–
PPV23 (1 dose)		£20,227.3	132,546,963	£159.6	−91,375	Dominated
PCV20→PPV23		£20,303.0	132,638,681	£235.3	343	£686,948
PPV23+PPV23		£20,392.7	132,547,656	£89.7	−91,024	Dominated
PCV15→PPV23		£20,416.4	132,608,379	£113.4	−30,302	Dominated

Table 3. Incremental results of base case, subgroup, and sensitivity analyses comparing PCV20 alone vs. PPV23 (single dose) among moderate- and high-risk adults aged 18–64 and all adults aged 65–99 years in England (N = 15,635,909).

			Subgroup			Sensitivity Analyses*
		Base Case	Moderate- and High-Risk Aged 18–64 Years	All Aged 65–99 Years		Hosp. CAP Rates from Pick et al.	2x Hosp. CAP Rates from Pick et al.	Plus Outpatient CAP	LT Consequences of IPD & CAP	VE-PPV23 vs. VT-CAP from Lawrence et al.	VE-PCV20 vs. ST3 CAP from Gessner et al.	Differential Discounting	Alt. Vaccine Waning	RWE of Vaccines
Clinical Outcomes
	No. of cases
	IPD	−7,789	−1,892	−5,897		−8,021	−7,927	−7,789	−7,043	−7,815	−7,651	−7,789	−6,617	−5,874
	All-cause hospitalized CAP	−140,046	−22,355	−117,691		−41,037	−80,087	−140,046	−119,221	−105,222	−165,231	−140,046	−118,323	−194,477
	All-cause outpatient CAP	–	–	–		–	–	−61,501	–	–	–	–	–	–
	No. of deaths
	IPD	−2,420	−287	−2,134		−2,516	−2,475	−2,420	−2,217	−2,431	−2,384	−2,420	−2,003	−1,810
	All-cause hospitalized CAP	−19,779	−1,936	−17,843		−6,209	−12,021	−19,779	−49,847	−15,201	−23,599	−19,779	−16,511	−27,754
	Life-years (discounted)	118,197	24,262	93,935		41,291	69,316	118,197	284,236	91,657	136,570	145,090	103,952	155,186
	Quality-adjusted life-years (discounted)	91,375	19,081	72,293		30,981	52,837	91,588	192,331	69,875	105,485	109,906	80,521	120,158
Economic Outcomes (in millions)
	Medical care	−£538.3	−£85.8	−£452.5		−£178.2	−£318.7	−£540.4	−£469.4	−£411.8	−£627.1	−£538.3	−£470.5	−£723.0
	Vaccination	£378.7	£78.7	£300.0		£378.7	£378.7	£378.7	£378.7	£378.7	£378.7	£378.7	£378.7	£378.7
	Medical + vaccination	−£159.6	−£7.2	−£152.4		£200.5	£60.0	−£161.7	−£90.7	−£33.1	−£248.4	−£159.6	−£91.8	−£344.3
Cost-Effectiveness
	Cost per LY	Dominant	Dominant	Dominant		£4,857	£865	Dominant	Dominant	Dominant	Dominant	Dominant	Dominant	Dominant
	Cost per QALY	Dominant	Dominant	Dominant		£6,473	£1,135	Dominant	Dominant	Dominant	Dominant	Dominant	Dominant	Dominant

LT: long-term; RWE: real world effectiveness; ST3: serotype 3

*Detailed information on parameter values employed in sensitivity analyses can be found in Supplement A

Figure 3. Scatterplot for cost-effectiveness of PCV20 alone versus PPV23 (single dose) among moderate- and high-risk adults aged 18–64 years and all adults aged 65–99 years in England (N = 15,635,909).WTP: willingness-to-pay

Figure 4. Cost-effectiveness acceptability curve for alternative pneumococcal vaccination strategies among moderate- and high-risk adults aged 18–64 years and all adults aged 65–99 years in England (N = 15,635,909).CEAF: cost-effectiveness acceptability frontier*The CEAF illustrates the probability of greatest net monetary benefit