Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23

Figures & data

Table 1. Clinical inputs to the model: population size, incidence, mortality, utilities, and vaccine serotypes.

	18–49 years (n = 2,363,294)			50–64 years (n = 1,137,639)			65–74 years (n = 649,539)			75–84 years (n = 356,629)			85–99 years (n = 119,555)			Sources
	Low risk	Moderate risk	High risk	Low risk	Moderate risk	High risk	Low risk	Moderate risk	High risk	Low risk	Moderate risk	High risk	Low risk	Moderate risk	High risk
Risk distribution, % of n	92.93%	4.55%	2.51%	78.85%	13.80%	7.35%	62.9%	22.53%	14.53%	47.37%	32.41%	20.23%	30.12%	49.37%	20.51%	^43^,^44
Incidence per 100,000
Sepsis	1.54	15.79	29.84	1.54	24.42	29.84	6.30	33.71	54.62	6.30	49.89	54.62	6.30	76.25	54.62	^43^,^44
Meningitis	0.61	1.89	0.70	0.61	1.89	0.70	2.12	3.89	4.45	2.12	3.89	4.45	2.12	3.89	4.45	^43^,^44
IP pneumonia	82.36	846.10	878.61	180.41	1,534.32	2,266.84	359.97	2,719.53	3,792.25	854.26	4,933.34	5,784.52	3,714.30	8,826.49	9,130.70	^43^,^44
OP pneumonia	470.87	533.80	968.28	2,106.81	668.80	1,255.50	7,047.81	1,093.90	1,696.31	2,1378.68	1,735.80	2,781.47	7,7845.64	2,639.00	6,351.60	^43–45
Mortality per 100 people (general population)
General population	0.05	0.22	0.49	0.32	0.84	2.38	0.91	1.96	4.65	2.63	4.95	7.85	18.71	14.93	15.07	^43
Mortality per 100 cases of illness
Sepsis	20.98	1.81	2.34	20.98	1.81	2.34	16.81	25.00	28.27	16.81	25.00	28.27	16.81	25.00	28.27	[44]
Meningitis	5.26	0.00	0.00	5.26	0.00	0.00	15.38	32.00	11.76	15.38	32.00	11.76	15.38	32.00	11.76	^43
IP pneumonia	0.11	0.65	1.90	0.48	0.93	1.98	1.36	2.44	2.07	3.16	3.88	4.05	8.94	11.14	19.80	^43^,^44^,^46
OP pneumonia	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Assumption
Utilities
General population utilities	0.9564	0.7745	0.7346	0.9335	0.7234	0.6852	0.9283	0.7308	0.7082	0.8921	0.6799	0.6607	0.8191	0.6038	0.5643	^47
Disutility
Sepsis	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	^48
Meningitis	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	^48
IP pneumonia	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	−0.13	^48
OP pneumonia	−0.13	0	0	0	0	0	0	0	0	0	0	0	0	0	0	Assumption
Vaccine serotype coverage (percentage of IPD due to vaccine serotypes)
PCV20	69.2%	69.2%	69.2%	69.2%	69.2%	69.2%	62.6%	62.6%	62.6%	62.6%	62.6%	62.6%	62.6%	62.6%	62.6%	^49
PPV23	78.7%	78.7%	78.7%	78.7%	78.7%	78.7%	74.1%	74.1%	74.1%	74.1%	74.1%	74.1%	74.1%	74.1%	74.1%	^49

Abbreviations. IP, inpatient; IPD, invasive pneumococcal disease; OP, outpatient; PCV13, 13-valent pneumococcal conjugate; PCV20, 20-valent pneumococcal conjugate; PPV23, 23-valent pneumococcal polysaccharide vaccine. Population size (n) in each age group is based on data from Statistics Denmark⁴⁴. Pneumococcal CAP was considered to constitute 20% of all cases of CAP and was assumed to have the same serotype distribution as IPD.

Figure 1. Model stages and transitions. Abbreviations. IP, inpatient; IPD, invasive pneumococcal disease; OP, outpatient.

Table 2. PCV20 and PPV23 efficacy against vaccine-related diseases.

	IPD					Pneumonia
	Year 1	Year 5	Year 10	Year 15	Year 16+	Year 1	Year 5	Year 10	Year 15	Year 16+
PCV20
18–49 years
Low risk	81.5% (47.9–96.5)	81.5% (47.9–96.5)	63.1% (37.1–74.7)	37.2% (21.9–44.1)	0.0% (0.0–0.0)	55.6% (22.7–78.7)	55.6% (22.7–78.7)	43.0% (17.5–60.9)	25.4% (10.4–36.0)	0.0% (0.0–0.0)
Moderate risk	81.5% (47.9–96.5)	81.5% (47.9–96.5)	63.1% (37.1–74.7)	37.2% (21.9–44.1)	0.0% (0.0–0.0)	55.6% (22.7–78.7)	55.6% (22.7–78.7)	43.0% (17.5–60.9)	25.4% (10.4–36.0)	0.0% (0.0–0.0)
High risk	65.2% (38.3–77.2)	65.2% (38.3–77.2)	50.5% (29.6–59.7)	29.8% (17.5–35.3)	0.0% (0.0–0.0)	44.5% (18.1–63.0)	44.5% (18.1–63.0)	34.4% (14.0–48.7)	20.3% (8.3–28.8)	0.0% (0.0–0.0)
50–64 years
Low risk	79.2% (46.5–93.7)	79.2% (46.5–93.7)	61.2% (36.0–72.5)	36.2% (21.2–42.8)	0.0% (0.0–0.0)	51.3% (20.9–72.2)	51.3% (20.9–72.2)	39.7% (16.2–56.2)	23.5% (9.6–33.2)	0.0% (0.0–0.0)
Moderate risk	79.2% (46.5–93.7)	79.2% (46.5–93.7)	61.2% (36.0–72.5)	36.2% (21.2–42.8)	0.0% (0.0–0.0)	51.3% (20.9–72.2)	51.3% (20.9–72.2)	39.7% (16.2–56.2)	23.5% (9.6–33.2)	0.0% (0.0–0.0)
High risk	63.3% (37.2–75.0)	63.3% (37.2–75.0)	49.0% (28.8–58.0)	28.9% (17.0–34.3)	0.0% (0.0–0.0)	41.1% (16.7–58.2)	41.1% (16.7–58.2)	31.8% (12.9–45.0)	18.8% (7.6–26.6)	0.0% (0.0–0.0)
≥65 years
Low risk	75.0% (44.1–88.8)	75.0% (44.1–88.8)	58.0% (34.1–68.7)	34.3% (20.1–40.6)	0.0% (0.0–0.0)	45.0% (18.3–63.7)	45.0% (18.3–63.7)	34.8% (14.2–49.3)	20.6% (8.4–29.1)	0.0% (0.0–0.0)
Moderate risk	75.0% (44.1–88.8)	75.0% (44.1–88.8)	58.0% (34.1–68.7)	34.3% (20.1–40.6)	0.0% (0.0–0.0)	45.0% (18.3–63.7)	45.0% (18.3–63.7)	34.8% (14.2–49.3)	20.6% (8.4–29.1)	0.0% (0.0–0.0)
High risk	60.0% (35.2–71.0)	60.0% (35.2–71.0)	46.4% (27.3–55.0)	27.4% (16.1–32.5)	0.0% (0.0–0.0)	36.0% (14.7–51.0)	36.0% (14.7–51.0)	27.9% (11.3–39.4)	16.4% (6.7–23.3)	0.0% (0.0–0.0)
PPV23
18–49 years
Low risk	59.1% (40.1–72.7)	45.1% (30.6–55.4)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
Moderate risk	32.8% (22.3–40.4)	25.0% (17.0–30.8)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
High risk	17.1% (11.6)	13.0% (8.8–16.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
50–64 years
Low risk	58.3% (39.8–72.1)	44.4% (30.3–54.9)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
Moderate risk	32.3% (22.1–40.0)	24.6% (16.8–30.5)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
High risk	16.8% (11.5–20.8)	12.8% (8.8–15.2)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
65–74 years
Low risk	55.7% (38.1–69.1)	42.5% (29.1–52.6)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
Moderate risk	30.9% (21.2–38.4)	23.5% (16.1–29.2)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
High risk	16.1% (11.0–20.0)	12.2% (8.4–15.2)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
75–84 years
Low risk	50.8% (34.6–62.8)	38.7% (26.4–47.8)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
Moderate risk	28.1% (19.2–34.9)	21.5% (14.7–26.6)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
High risk	14.6% (10.0–18.1)	11.1% (7.6–13.8)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
85–99 years
Low risk	37.9% (25.6–46.5)	28.9% (19.5–35.4)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
Moderate risk	20.5% (14.2–25.8)	15.6% (10.9–19.7)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–
High risk	10.6% (7.4–13.4)	8.1% (5.6–10.2)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	0.0% (0.0–0.0)	–	–	–	–	–

Note. The vaccine efficacy of PCV20 is assumed equal to PCV13 and is based on Essink et al. ⁵⁴. The waning of PCV20 is based on a study by Mangen et al. ⁵¹, and it was assumed to be 5% between years 6 and 10, and 10% between years 11 and 16. After year 16, it was assumed that the PCV20 has no efficacy. The vaccine efficacy and waning of PPV23 against IPD was based on surveillance data from Public Health England in the period from 2000 to 2017⁴⁰ and no efficacy against CAP was assumed. Vaccine waning for PPV23 is based on Djennad et al.⁴⁰. Beyond the first year after administration, a linear decline to 76.2% of initial vaccine efficacy by year 5 was assumed, and from there, a linear decline to no efficacy by year 10 was assumed.

Table 3. Cost inputs including treatment-related costs, cost of patient time, transportation time and vaccine cost.

	Treatment-related costs		Patient time^a			Transportation^b
	Costs, EUR	Sources	Time-use, hours	Total cost, EUR	Sources	Number of contacts	Total cost, EUR	Sources
Vaccine administration, primary care sector	40.0	^55	1	24.3	Assumption	2	9.4	Assumption
OP pneumonia^c	0.0	Assumption	0	0.0	Assumption	0	0.0	Assumption
IP pneumonia
Hospital sector (18–84 years)	11,523.2	^56	431.3	10,499.8	^56^,^57	10	188.3	^56
Hospital sector (85+ years)	8,954.9	^56	431.3	10,499.8	^56^,^57	10	188.3	^56
Primary care sector (18–84 years)	100.7	^56	2.5	60.9	^56	5	23.6	^56
Primary care sector (85+ years)	100.7	^56	2.5	60.9	^56	5	23.6	^56
Municipality (18–84 years)^d	11,110.0	^56	0	0.0	Assumption	0	0.0	Assumption
Municipality (85+ years)^d	8,655.1	^56	0	0.0	Assumption	0	0.0	Assumption
IPD (sepsis and meningitis)
Hospital sector	16,231.7	^58	259.5	6,317.4	^57^,^58	4	75.3	^58
Primary care sector	417.2	^58	1	24.3	^58	2	9.6	^58
Municipality^d	60.359.6	^58	0	0.0	Assumption	0	0.0	Assumption
Vaccine cost
PPV23, unit cost	39.7	^59
PCV20, unit cost	120.7	^59

Note. ^aThe cost of patient time is based on an hourly rate of EUR 24.3⁶⁰. The time spent on transportation is assumed to be 30 min per visit to the hospital and 15 min per visit in the primary care sector. The time spent while visiting the primary care sector is 15 min per visit. The duration of hospitalization is based on the DRG groups 04MA13–04MA16 (pneumonia) and 01MA03–18MA01 (IPD)⁵⁷. The cost of patient time during hospital admission is calculated based on an assumption of 16 h per day, as it was assumed that patients sleep for 8 h per day. ^bThe cost of transportation is set to EUR 18.8 per hospital visit and EUR 4.7 per visit to the primary care sector⁶⁰. ^cIt is assumed that patients with OP pneumonia do not receive any treatment, and consequently, no costs are associated with these patients. ^dIt is assumed that there are no patient time and transportation costs involved in municipality care services, as it takes place in the patient’s own home.

Table 4. Results – PCV20 as a reimbursed vaccine in the scenario with vaccination of Danish adults aged ≥18 at moderate or high risk as well as all Danes aged ≥65 years.

		PPV23	PPV23+PCV20	Difference
Clinical outcomes
IPD (no. of cases)	Sepsis	24,897	24,595	−302
	Meningitis	3,118	3,090	−29
All-cause CAP (no. of cases)	Hospitalized	2,544,172	2,540,038	−4,135
	Requiring outpatient care only	10,858,807	10,845,205	−13,602
Mortality (no. of cases)	IPD	6,954	6,874	−80
	All-cause CAP	166,874	166,640	−234
Life years (discounted), total [per person]		82,431,939 [17.817]	82,433,373 [17.817]	1,433 [0.000]
Quality-Adjusted Life Years (discounted), total [per person]		71,832,108 [15.526]	71,833,457 [15.526]	1,350 [0.000]
Economic outcomes (discounted), EUR
Total cost, total [per person]		35,911,862,088 [7,767]	35,852,043,523 [7,754]	−59,818,565 [13]
	Vaccine cost	44,996,741	76,744,790	31,748,049
	Hospital cost	12,169,572,775	12,129,922,240	−33,598,035
	Primary care sector cost	134,667,210	144,840,087	10,172,878
	Municipality cost	11,546,046,287	11,511,688,871	−34,357,416
	Patient cost	12,016,579,076	11,988,847,534	−27,731,542
ICER (total), EUR
Cost per life year				−41,736 (PCV20 dominant strategy)
Cost per QALY				−44,326 (PCV20 dominant strategy)

Note. The table shows the accumulated results for life years, QALY, and total costs. Results per person in the model are shown in “[]”. The total population in the first cycle is 490,741 people in both vaccine strategies.

Abbreviations. QALY, quality-adjusted life years; ICER, incremental cost-effectiveness ratio; CAP, community-acquired pneumonia, IPD: invasive pneumococcal disease.

Table 5. Results – PCV20 as a NIP vaccine in the scenario with vaccination of Danish adults aged ≥18 years at moderate or high risk as well as all Danes aged ≥65 years.

		PPV23	PCV20	Difference
Clinical outcomes
IPD (no. of cases)	Sepsis	24,897	23,715	−1,182
	Meningitis	3,118	3,008	−110
All-cause CAP (no. of cases)	Hospitalized	2,544,172	2,526,708	−17,464
	Requiring outpatient care only	10,858,807	10,801,388	−57,419
Mortality (no. of cases)	IPD	6,954	6,644	−310
	All-cause CAP	166,874	165,904	−969
Life years (discounted), total [per person]		82,431,939 [17.817]	82,438,065 [17.818]	6,125 [0.001]
Quality-Adjusted Life Years (discounted),  total [per person]		71,832,108 [15.526]	71,837,929 [15.527]	5,821 [0.001]
Economic outcomes (discounted), EUR
Total cost, total [per person]		35,911,862,088 [7,767]	35,515,746,203 [7,710]	−396,115,884 [86]
	Vaccine cost	44,996,741	136,627,159	91,630,419
	Hospital cost	12,169,572.775	11,995,928,393	−173,644,382
	Primary care sector cost	134,667,210	133,162,858	−1,504,352
	Municipality cost	11,546,046,287	11,394,309,739	−151,736,547
	Patient cost	12,016,579,076	11,855,718,053	−160,861,022
ICER (total), EUR
Cost per life year				−64,669 (PCV20 dominant strategy)
Cost per QALY				−68,054 (PCV20 dominant strategy)

Note. The table shows the accumulated results for life years, QALY, and total costs. Results per person in the model are shown in “[]”. The total population in the first cycle is 490,741 people in both vaccine strategies.

Abbreviations. QALY, quality-adjusted life years; ICER, incremental cost-effectiveness ratio; CAP, community-acquired pneumonia; IPD, invasive pneumococcal disease.

Table 6. Results of deterministic sensitivity analyses – PCV20 as a reimbursed vaccine.

	Analysis	Variable	Scenarios
			Adults aged ≥18 years at moderate risk/high risk and all aged ≥65 years	All aged ≥50 years	All aged ≥65 years	Aall aged ≥65 years at moderate risk/high risk
Uptake: PPV23 = 73% → PCV20 =  25% versus PPV23 = 73%	Base cases: lifetime and vaccine effect CAP PPV23 = 0%	Δ QALY	1,350	1,464	994	852
		Δ Costs (EUR)	−59.8 million	−42.5 million	−43.3 million	−49.0 million
		ICER (EUR/QALY)	−44,316	−29,031	−43,504	−57,478
	Sensitivity analysis 1: time horizon 5 years	Δ QALY	249	251	201	171
		Δ Costs (EUR)	11.9 million	36.1 million	7.0 million	−7.8 million
		ICER (EUR/QALY)	47,988	144,042	34,842	−45,779
	Sensitivity analysis 2: time horizon 10 years	Δ QALY	688	708	553	471
		Δ Costs (EUR)	−31.6 million	−9.7 million	−24.6 million	−33.9 million
		ICER (EUR/QALY)	−45,911	−13,651	−44,464	−72,022
	Sensitivity 3: PPV23 vaccine efficacy against CAP (Lawrence and Suzuki (waning))	Δ QALY	1,314	1,426	975	839
		Δ Costs (EUR)	−55.6 million	−37.8 million	−41.2 million	−47.5 million
		ICER (EUR/QALY)	−42,296	−26,492	−42,196	−56,687
	Sensitivity 4: Health sector perspective	Δ QALY	1,350	1,464	994	852
		Δ Costs (EUR)	−32.1 million	−16.8 million	−22.8 million	−29.8 million
		ICER (EUR/QALY)	−23,771	−11,454	−22,979	−35,006
	Sensitivity 5: PPV23 vaccine efficacy based on Falkenhorst et al.^65	Δ QALY	1,187	1,279	866	758
		Δ Costs (EUR)	−45.2 million	−26.4 million	−31.9 million	−41.1 million
		ICER (EUR/QALY)	−38,031	−20,605	−36,844	−54,168
	Sensitivity 6: 10% price reduction of PCV20 and PPV23	Δ QALY	1,350	1,464	994	852
		Δ Costs (EUR)	−63.0 million	−47.2 million	−45.5 million	−50.0 million
		ICER (EUR/QALY)	−46,668	−32,232	−45,798	−58,718
	Sensitivity 7: 10% price increase of PCV20 and PPV23	Δ QALY	1,350	1,464	994	852
		Δ Costs (EUR)	−56.6 million	−37.8 million	−41.0 million	−47.9 million
		ICER (EUR/QALY)	−41,964	−25,830	−41,211	−56,239

Abbreviations. ICER, incremental cost-effectiveness ratio; QALY, Quality-adjusted life years.

Table 7. Results of base case analyses and deterministic sensitivity analyses – PCV20 as a NIP vaccine.

	Analysis	Variable	Scenarios
			18+ at moderate risk/ high risk and all aged  ≥ 65 years	All aged  ≥ 50 years	All aged  ≥ 65 years
Uptake: PPV23 = 73% versus PCV20 = 73%	Base cases: lifetime and vaccine effect CAP PPV23 = 0%	Δ QALY	5,821	6,180	4,358
		Δ Costs (EUR)	−396.0 million	−376.3 million	−290.4 million
		ICER (EUR/QALY)	−68,039	−60,896	−66,634
	Sensitivity analysis 1: time horizon 5 years	Δ QALY	1,571	1,571	1,287
		Δ Costs (EUR)	−137.5 million	−95.3 million	−108.4 million
		ICER (EUR/QALY)	−87,541	−60,652	−84,236
	Sensitivity analysis 2: time horizon 10 years	Δ QALY	3,391	3,453	2,747
		Δ Costs (EUR)	−303.2 million	−269.4 million	−228.6 million
		ICER (EUR/QALY)	−89,440	−78,016	−83,233
	Sensitivity 3: PPV23 vaccine efficacy against CAP (Lawrence and Suzuki (waning))	Δ QALY	5,489	5,831	4,182
		Δ Costs (EUR) (EUR/QALY)	−356.3 million	−332.6 million	−270.7 million
		ICER	−64,921	−57,032	−64,729
	Sensitivity 4: Health sector perspective	Δ QALY	5,821	6,180	4,358
		Δ Costs (EUR)	−235.2 million	−208.4 million	−171.1 million
		ICER (EUR/QALY)	−40,408	−33,719	−39,255
	Sensitivity 5: PPV23 vaccine efficacy based on Falkenhorst et al.^65	Δ QALY	4,839	5,075	3,572
		Δ Costs (EUR)	−306.4 million	−278.5 million	−220.3 million
		ICER (EUR/QALY)	−63,327	−54,874	−61,682
	Sensitivity 6: 10% price reduction of PCV20 and PPV23	Δ QALY	5,821	6,180	4,358
		Δ Costs (EUR)	−405.2 million	−389.7 million	−297.0 million
		ICER (EUR/QALY)	−69,612	−63,059	−68,160
	Sensitivity 7: 10% price increase of PCV20 and PPV23	Δ QALY	5,821	6,180	4,358
		Δ Costs (EUR)	−386.9 million	−362.9 million	−283.7 million
		ICER (EUR/QALY)	−66,465	−58,732	−65,108

Abbreviations. ICER, incremental cost-effectiveness ratio; QALY, Quality-adjusted life years.

Figure 2. Probabilistic sensitivity analysis results of Danish adults aged ≥18 years at high and moderate risk and all Danes aged ≥65 years in the two potential vaccination situations. (a) cost-effectiveness plane for PCV20 as a reimbursed vaccine and (b) cost-effectiveness plane for PCV20 as a NIP vaccine.

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Data availability statement

All input data used in the model are publicly available or can be retrieved from the Danish National Patient Register, the Danish Cause of Death Register, and other publicly available sources. The model will not be shared.