A few years later

Figures & data

Table 1. Differences in health outcomes between the two vaccines in scenario 1

	Children < 5 y	Others (indirect effects)
Disease cases avoided
Total invasive pneumococcal disease	3.20	140.4
Of which caused by: serotype 3	0.41	41.4
serotype 6A	0.15	11.1
serotype 19A	2.63	87.9
Pneumonia, treated in the hospital	20.0	-
Pneumonia, treated by GP only	52.3	-
Acute Otitis Media (AOM)	858.9	-
Sequelae avoided
Death	0.15	40.5
Physical handicap	0.16	-
Deafness	0.26	-

Table 2. Cost-effectiveness results in various scenarios at a price difference of €11 per dose.^a

	Incremental (PCV13 over PCV10)
	QALYs	Total Costs	ICER^b
		(x € 1,000)
Scenario 1
Direct effects, IPD only	10	7400	€ 670 000 (€ 394 000–1 500 000)
Direct and indirect effects, IPD only	400	5900	€ 14 500 (€ 11 100–19 200)
Direct and indirect effects, IPD + non invasive disease	440	5600	€ 12 700 (€ 9100–11 100)
Other scenarios (direct + indirect effects IPD + non invasive disease)
2 Epidemiology based on Dutch post-PCV7 data			€ 17 200 (€ 12 200–23 600)
3 Efficacy PCV10 against IPD and pneumonia based on FINIP			€ 17 400 (CI N/A)^b
4 Extra protection PCV10 against NTHi based on COMPAS			€ 24 600 (CI N/A)^b
5 Extra protection PCV10 against NTHi based on POET			€ 124 000 (CI N/A)^b
6 No cross-protection from PCV10 against serotype 19A			€ 11 900 (€ 8200–16 200)
7 Cross-protection from PCV10 against serotype 19A includes herd immunity			€ 16 000 (€ 11 000–22 800)
8 No reduced protection from PCV13 against serotype 3			€ 5 800 (€ 3500–8100)
9 No herd protection PCV13 against serotype 3			€ 14 500 (€ 10 400–19 400)
10 Excluding effects on pneumonia			€ 13 200 (€ 9400–17 800)
11 Herd protection and replacement based on UK data			€ 4700 (€ 2800–6500)
12 Reduced indirect effects based on UK-data (25%)			€ 25 500 (€ 17 700–33 500)

^a QALY, Quality Adjusted Life Year. QALYs rounded to nearest tens, costs and ICERs rounded to nearest € 100; ICERs above € 100 000 rounded to the nearest € 1000;^b 95% confidence interval (CI) given, when the difference in QALYs is significantly different from zero. Otherwise: CI N/A (not applicable)

Figure 1. Cost-effectiveness by price difference, for three selected scenarios.

Table 3. Number of cases per year of invasive pneumococcal disease (IPD)

	Post-PCV7	Post-PCV10
	Apr 06 – Mar 2011	Apr 2011 – Mar 2013	Change
IPD cases in children younger than five years of age.^15
Caused by serotypes covered in PCV7^a	28,8	10,1	-19 (-65%)
Caused by serotypes covered in PCV10, not PCV7^b	29,6	20,2	-9 (-32%)
Caused by serotype 3	11,2	2,5	-9 (-77%)
Caused by serotype 6A	3,2	0,0	-3 (-100%)
Caused by serotype 19A	1,6	7,6	+6 (+374%)
Caused by serotypes not covered in PCV13	32,8	58,1	+25 (+77%)
IPD cases in patients between five and 64 y of age.^15
Caused by serotypes covered in PCV7^a	288,0	106,1	-182 (-63%)
Caused by serotypes covered in PCV10, not PCV7^b	315,2	492,6	+177 (+56%)
Caused by serotype 3	52,8	88,4	+36 (+67%)
Caused by serotype 6A	11,2	0,0	-11 (-100%)
Caused by serotype 19A	54,4	164,2	+110 (+202%)
Caused by serotypes not covered in PCV13	319,2	591,2	+272 (+85%)
IPD cases in patients older than five years of age.^15
Caused by serotypes covered in PCV7^a	439,2	138,9	-300 (-68%)
Caused by serotypes covered in PCV10, not PCV7^b	231,2	356,2	+125 (+54%)
Caused by serotype 3	89,6	151,6	+62 (+69%)
Caused by serotype 6A	28,8	25,3	-4 (-12%)
Caused by serotype 19A	94,4	255,2	+161 (+170%)
Caused by serotypes not covered in PCV13	470,4	970,1	+500 (+106%)

^a Includes serotypes 4, 6B, 9V, 14, 18C, 19F, 23F;^b Includes serotypes 1, 5, 7F

Table 4. Indirect effects - herd protection and serotype replacement.^a

	Dutch data^8	UK data^6
Percentage change in non-VT IPD, for age group:
< 2 y	1.37 (0.77;2.46)	1.68 (1.37;2.06)
2–4 y	1.22 (0.47;3.18)	1.82 (1.30;2.55)
5–14 y	1.58 (0.77;3.26)	0.82 (0.64;1.04)
15–44 y	1.22 (0.96;1.54)	0.85 (0.71;1.02)
45–64 y	1.37 (1.11;1.70)	0.96 (0.87;1.06)
65+ year	1.25 (1.09;1.43)	1.48 (1.32;1.65)
Percentage change in VT IPD, for age group:
< 2 y	0.01 (0.01;0.02)^b	0.02 (0.01;0.05)
2–4 y	0.19 (0.06;0.66)	0.07 (0.04;0.13)
5–14 y	0.36 (0.12;1.14)	0.25 (0.16;0.38)
15–44 y	0.81 (0.59;1.29)	0.12 (0.07;0.21)
45–64 y	0.46 (0.33;0.63)	0.15 (0.12;0.18)
65+ year	0.45 (0.37;0.55)	0.19 (0.14;0.25)

^a Mean and confidence interval; IPD, invasive pneumococcal disease; VT, Vaccine-type; ^b No change in VT IPD in the original data; a continuity correction of 0.5 was applied, with an assumed confidence interval of Exp(ln(0.01)*1.1) to Exp(ln(0.01)*0.9).

Table 5. Epidemiological data on non-invasive disease in children younger than 5 y of age

	Post-PCV7	Post-PCV10
	Apr 2006-Mar 2011	Apr 2011-Dec 2012
Number of pneumonia cases per 100,000 inhabitants per year (Source: personal communication Kiwa Carity).
0 y of age	0,23	0,64
1 y of age	0,47	1,74
2 y of age	0,39	1,61
3 y of age	0,27	1,51
4 y of age	0,29	1,54
Number of acute otitis media (AOM) cases per 100,000 inhabitants (Source: personal communication Primary Care Database).
0 y of age	1,57	4,58
1 y of age	5,33	15,01
2 y of age	3,96	10,88
3 y of age	2,10	7,74
4 y of age	2,02	7,14
Number of GP contacts per acute otitis media (AOM) case (Source: personal communication Primary Care Database).
0 y of age	1,71	1,67
1 y of age	1,95	2,03
2 y of age	1,66	1,69
3 y of age	1,51	1,50
4 y of age	1,43	1,47

Table 6. Efficacy estimates used in the study

	Scenarios	Reduction of disease cases^1	Source
Invasive pneumococcal disease (IPD)
Reduction of vaccine-type IPD cases.	1,2,5–12	93.9% (0.029)	^23
(...), for PCV10.	3	100.0% (0.026) (Maximized at 100%)	^11
Non-invasive disease ^2
Reduction of all-cause AOM, using PCV7.	1–8,11,12	6.0% (0.051)	^25
(...), using PCV10.	3	19.0% (0.069)	^13
(...), using PCV10.	4	33.6% (0.060)	^16
Reduction of number of pneumonia cases, as seen by a general practitioner, using PCV7.	1–10,12	6.0% (0.032)	^24
Reduction of number of pneumonia cases, admitted in a hospital, using PCV7.	1–10,12	11.1% (0.043)	^24
(...), using PCV10.	3	28.6% (0.043)	^11

(1)Mean (standard deviation) used in the probabilistic sensitivity analysis, using a normal distribution;² Efficacy for non-invasive disease recalculated to vaccine-type, assuming a serotype distribution and assuming only disease cases caused by vaccine-type serotypes or non-typable H. influenzae (acute otitis media for PCV10) will be affected.

Table A1. Detail of studies used to calculate vaccine efficacy.¹

Name of the study	Source
Kaiser Permanente Vaccine Study	^23 ^, ^24	PCV7 vs. meningococcal vaccine (control) USA (Northern California) Aim: To evaluate protective efficacy of PCV7 against invasive pneumococcal disease caused by vaccine serotypes, clinical episodes of otitis media and episodes of pneumonia.
Finnish Otitis Media Vaccine Trial	^25	PCV7 vs. hepatitis vaccine (control) Finland Aim: To evaluate protective efficacy of PCV7 against episodes of acute otitis media.
Pneumococcal Otitis Efficacy Trial (POET)	^16	PCV11 vs. hepatitis vaccine (control) Czech Republic and Slovakia. Aim: to evaluate protective efficacy against acute otitis media caused by pneumococci and nontypable H. influenza.
Finnish Invasive Pneumococcal disease (FinIP)	^11	PCV10 vs. hepatitis vaccine (control) Finland Aim: To evaluate protection against several disease endpoints associated with S. pneumoniae and non-typeable H. influenzae.
Clinical Otitis Media and Pneumonia Study (COMPAS)	^13	PCV10 vs. hepatitis vaccine (control) Latin America Aim: to evaluate protective efficacy against acute otitis media.

(1) PCV: Pneumococcal Conjugate Vaccine

Table A2. Parameters used in the health-economic model

	Parameter used	Source
Vaccine effectiveness
Effectiveness after dose 2 mo	0.0%	Assumption
Effectiveness after dose 3 mo	30.0%	Assumption
Effectiveness after dose 4 mo	90.0%	Assumption
Effectiveness after booster dose (11 mo)	100.0%	Assumption
Vaccination level. first three shots	95.7%	^28
Sequalae
Case fatality rate
0–2 y	6.0%	^29
3–4 y	4.8%	^29
Physical handicap (Mental retardation, spasticity, epilepsy)	6.0%	^29
Needing institutionalized care	25.0%	^30
Needing special education	50.0%	^30
Hearing problems	9.5%	^29
Percentage needing cochlear device	37.5%	^29
Quality of life weights
Per year
Mental retardation	0.620	^31
Spasticity	0.619	^32
Epilepsy	0.830	^31
Slight hearing problems	0.910	^31
Bilateral hearing problems (first year)	0.550	^33
Bilateral hearing problems (cochlear device)	0.820	^33
Death	0.000	Assumption
All other states	0.890	Assumption
Hospital admission for non-inv pneumonia	0.930	^34
Non-inv pneumonia treated by GP	0.930	^34
AOM	0.980	^34
Per Episode
Hospital admission for meningitis	0.070	^34

Table A3. Cost parameters used in the health-economic model.¹

Direct costs	Direct costs	Indirect costs
Invasive pneumococcal disease (IPD)
0–1 y	€6773.42	€781.24
2–4 y	€2732.31	€335.80
Non-invasive disease
Non-invasive pneumonia (admitted to hospital)	€2809.59	€338,23
Non-invasive pneumonia (seen by GP)	€28.42	€123,89
Acute otitis media (simple)	€18.75	€65,66
Acute otitis media (complex, tympanostomy)	€409.81	€247,78
Acute otitis media (complex, no tympanostomy)	€102.75	€61,95
Sequalea
Special education (annual costs)
Primary school (until age 12)	€10 527.77
High school (age 12–18)	€18 225.49
Intitutional care (annual costs)	€42 532.02
Cochlear implantation	€60 853.42

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