Article

Cost-effectiveness of new adult pneumococcal vaccination strategies in Italy

Department of Public Health
Human Vaccines & Immunotherapeutics (Impact Factor: 2.37). 01/2013; 9(3). DOI: 10.4161/hv.23268
Source: PubMed

ABSTRACT

Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy.

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RESEARCH PAPER
RESEARCH PAPER
*Correspondence to: Paolo Bonanni; Email: paolo.bonanni@uni.it
Submitted: 10/15/12; Accepted: 10/26/12
http://dx.doi.org/10.4161/hv.23268
Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among
elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal
polysaccharide vaccine (PPV23) has been dierently implemented in the Italian regions in the past years, reaching over-
all low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine
(PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012,
indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Ital-
ian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly.
Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their
sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact
of an adult pneumococcal vaccination program in Italy.
Particularly, dierent immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simulta-
neous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70
and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program.
In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic
impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact
of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis
(PM) cases, and related hopitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of
pneumococcal CAP by the European Medicine Agency (dierently from FDA, whose indications include all pneumo-
coccal diseases in subjects ≥ 50 y), the model calculated also the possible impact of vaccination on CAP cases (non-
bacteraemic), considering the rate of this disease due to S. pneumoniae. The results of the analysis show that, in Italy,
an age-based PCV13 vaccination program in elderly people is cost-eective from the payer perspective, with costs
per QALY ranging from 17,000 to 22,000 Euro, according to the adopted vaccination strategy. The subsequent PPV23
oer results in an increment of costs per QALY (from 21,000 to 28,000 Euro, according to the vaccination strategy ad-
opted). Pneumococcal vaccination using the conjugate vaccine turned out to be already favorable in the second year
of implementation, with incremental costs per QALY comparable to those of other already adopted prevention activi-
ties in Italy (for instance, universal HPV vaccination of 12 y-old girls), with further benets obtained when extending
the study period beyond the 5-y horizon of our analysis.
Cost-eectiveness of new adult pneumococcal
vaccination strategies in Italy
Sara Boccalini,
1
Angela Bechini,
1
Miriam Levi,
1
Emila Tiscione,
1
Roberto Gasparini
2
and Paolo Bonanni
1,
*
1
Department of Health Sciences; University of Florence; Florence, Italy;
2
Department of Health Sciences; University of Genoa; Genoa, Italy
Keywords: pneumococcal conjugate vaccine, elderly, economic evaluation, cost-effectiveness, pneumococcal disease
Introduction
Community-acquired pneumonia (CAP) and invasive pneu-
mococcal disease (IPD) are common pathologies among elderly
people, with a high disease burden for both the National Health
Service (NHS) and the society. In Italy, administration of the
23-valent pneumococcal polysaccharide vaccine (PPV23) is cur-
rently recommended to high-risks groups to prevent IPD in sub-
jects with specific comorbidities.
1
However, in Italy the PPV23
coverage is currently extremely low.
A 13-valent polysaccharide conjugate vaccine (PCV13)
(Prevenar® 13, Pfizer Vaccines) became available in Italy 2 y
ago with indication for protection against S. pneumoniae diseases
(invasive disease, pneumonia and acute otitis media) in chil-
dren aged 2 mo-5 y,
2
with different regional implementation
and vaccination coverage. Since October 2011, indications were
extended to subjects 50 y to prevent IPD (European Medicine
Agency, EMA) or all pneumococcal diseases (Food and Drug
Administration indication, FDA).
Italian decision-makers are challenged on how to update
recommendations for use of pneumococcal vaccination in
adults. Evaluating whether an age-based vaccination program
with PCV13 for elderly people may prove advantageous from
both a clinical and economic perspectives for the National and
Regional Health Services is a very up-to-date issue. According
to the World Health Organization (WHO) recommendations,
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700 Human Vaccines & Immunotherapeutics Volume 9 Issue 3
pharmaco-economic analyses represent useful tools for health
authorities and are required to value the feasibility of new
immunization programs in a setting of limited economic health
resources.
3
Our study aimed to assess the cost-effectiveness of age-based
vaccination scenarios with PCV13 in a limited time frame (5 y)
in subjects aged 65 y using the perspective of the NHS.
Results
The number of cases of PM, BPP and CAP avoided in 5 y since
implementation of PCV13 vaccination, compared with a no-vac-
cination scenario, are reported in Table 1. According to PCV13
efficacy data, the biggest impact of vaccination regarding absolute
number of cases is due to CAP reduction, while, in relative terms,
it is related to BPP and PM diseases. The administration of an
additional PPV23 dose increased the serotype coverage for invasive
diseases by 13.9%, thus increasing the number of prevented cases.
The number of deaths avoided after the introduction of pneu-
mococcal vaccination is shown also in Table 1. The number of
avoided deaths has a trend similar to the prevented cases of pneu-
mococcal diseases.
As a consequence of the avoided pneumococcal disease
cases, the adoption of an age-based immunization strategy with
PCV13 yields savings ranging from 7 million to 19 million
Euro. The administration of an additional dose of PPV23 gives
a marginal increase of savings. According to the above assump-
tions, the modeled immunization strategies cost 91–241 million
Table1. Avoided cases and deaths, and reduction rate (%) following the adoption of the vaccination program in 5 y vs. non-vaccination scenario
PCV13 Cases avoided Reduction rate (%)
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
Hopitalized CAP cases 1,646 3,112 4,323 2 5 6
Non-hopitalized CAP cases 3,529 6,674 9,270 2 5 6
Bacteraemic pneumococcal pneumo-
nia cases
303 572 1,197 6 4 9
Pneumococcal meningitis cases 71 134 198 6 12 18
Total cases 5,548 10,492 14,988 2 5 6
PCV13 + PPV23 Cases avoided Reduction rate (%)
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
Hopitalized CAP cases 1,646 3,112 4,323 2 5 6
Non-hopitalized CAP cases 3,529 6,674 9,270 2 5 6
Bacteraemic pneumococcal pneumo-
nia cases
329 623 1,303 7 5 10
Pneumococcal meningitis cases 77 145 214 7 13 19
Total cases 5,580 10,553 15,110 2 5 7
PCV13 Deaths avoided Reduction rate (%)
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
CAP cases 310 587 816 2 5 6
Bacteraemic pneumococcal pneumo-
nia cases
28 53 131 1 2 4
Pneumococcal meningitis cases 13 25 44 5 9 16
Total cases 351 665 991 2 4 6
PCV13 + PPV23 Deaths avoided Reduction rate (%)
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
CAP cases 310 587 816 2 5 6
Bacteraemic pneumococcal pneumo-
nia cases
30 57 143 1 2 5
Pneumococcal meningitis cases 14 27 47 5 10 17
Total cases 355 671 1.006 2 4 6
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Euro in 5 y. Adding the administration of a dose of PPV23, the
overall immunization campaign cost increases to 114–303 mil-
lion Euro (Table 2).
The net costs of PCV13 vaccination strategies, calculated as
the difference between immunization costs and health savings
due to the clinical cases avoided amount to 84 million Euro in
the single-cohort strategy, 156 million Euro in the double-cohort
strategy and 222 million Euro in the triple-cohort strategy. These
values increase to 107, 199 and 283 million Euro, respectively, in
the additional PPV23 administration scenario. Particularly, vac-
cination of 1 cohort per year determines a cost/QALY of 16,987
Euro, immunization of 2 cohorts per year 19,289 Euro and,
lastly, of 3 cohorts per year 22,109 Euro, respectively. The cost/
QALY increases to 21,493, 24,443 and 27,866 Euro, respectively,
including the sequential PCV13+PPV23 immunization (Table 2).
Considering cumulative net costs/QALY, pneumococcal vac-
cination of elderly subjects in Italy is already economically jus-
tified during the second year of immunization, independently
from the adopted strategy (Fig. 1).
Sensitivity analysis brought no significant change in the
overall profile of convenience of the three vaccination strategies
(Table 3). The rate of CAP due to S. pneumoniae is the most
relevant factor influencing the cost/QALY, but pneumococcal
vaccination remained economically justified under all assump-
tions. Notably, outcomes were not particularly influenced by the
reduction of PCV13 vaccination coverage (influencing both the
number of avoided cases and vaccination costs).
Discussion and Conclusions
S. pneumoniae diseases represent a relevant public health problem
in Italy, with a steady increase of notified cases in the last decades
(from 108 cases in 1994 to 851 in 2010), and with a consider-
able disease burden to the NHS, mostly due to hospitalization
and deaths. Particularly, in the last years, pneumococcal diseases
mainly involved subjects > 65 y. In 2009, 67% of notified cases
were theoretically preventable by PCV13 vaccination and 82%
by PPV23 immunization, according to serotype distribution of
isolates.
4
PCV13 replaced the previous PCV7 in the universal
vaccination of children, recently receiving the indication for use
in subjects > 50 y of age.
5
In a period of extremely scarce health resources, a popula-
tion model seemed particularly suitable to evaluate the impact
of vaccination programs in a relatively short time frame. Namely,
population models, differently from cohort models, allow us to
estimate the impact of a new vaccine program on total popula-
tion health during a fixed time period rather than focusing on a
cohort.
6-8
Table2. Savings/costs, net costs and ICERs obtained with the population
model in 5 y of follow-up (costs and savings expressed in Euro)
PCV13
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
Health savings 6,785,918 12,846,781 19,346,080
Vaccination costs 90, 8 87, 509 168,719,884 241,307,723
Vaccination net costs 84,101,591 155,873,103 221,961,644
Costs / avoided cases 15,158.93 14, 857.06 14,809.35
Costs / LYG 12,783.03 14,363.40 16,213.89
Costs / QALY 16,987.33 19,289.34 22,109.42
PCV13 + PPV23
1 cohort/
year
2 cohorts/
year
3 cohorts/
year
Health savings 6,985,556 13,228,692 20,005,336
Vaccination costs 114, 4 07, 827 212,632,744 303,189,701
Vaccination net costs 107,422,271 199,404,052 283,184,366
Costs / avoided cases 19,249.99 18,894.74 18,741.67
Costs / LYG 16,171. 52 18,198.38 20,428.15
Costs / QALY 21,493.32 24,443.04 27, 865. 63
Figure1. Cumulative net costs (Euro) per QALY during the 5 y of analysis.
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702 Human Vaccines & Immunotherapeutics Volume 9 Issue 3
Population models are frequently adopted in economic evalu-
ations of pneumococcal vaccination because they also include
effects due to herd protection and serotype replacement after
immunization.
6
Those two issues were not approached in our
model: studies on herd immunity after PCV13 vaccination
of elderly subjects are not yet available. A protective effect on
younger people and on unvaccinated elderly population might
occur. However, should that be the case, the outcomes of the
study would be even more favorable than reported in our simu-
lation. However, as it was described after universal vaccination
with PCV7 in children,
9-13
also a partial serotype replacement
might occur some years after the PCV13 vaccination of adults,
thus potentially reducing the long-term effectiveness of vaccina-
tion. Such effect would anyway be very unlikely in the first 5 y
since vaccination implementation. Therefore, we assumed that
effects of herd protection and serotype replacement following
vaccination were not relevant for the study.
The results of our evaluation show that vaccination of elderly
people with PCV13 brings to a relevant reduction of pneumococ-
cal diseases in 5 y. Considering clinical savings due to the imple-
mentation of PCV13 immunization, costs/QALY range from
17,000 to 22,000 Euro. PPV23 sequential administration causes
a slight increment of cost/QALY. However, the values of cost/
QALY stay largely under the threshold of 50,000 Euro, gener-
ally considered acceptable in economic studies. The only remark
for the sequential use of conjugate-polysaccharide vaccines is the
trade-off between potentially wider serotype coverage and poten-
tial effect of PPV23 on the memory B cell pool.
14
Cumulative net
cost/QALY are already favorable starting from the second year of
implementation in all vaccination scenarios. In addition, ICERs
are acceptable and comparable to those of other adopted preven-
tion activities in Italy (i.e., HPV vaccination in female adolescent
subjects).
15
The uncertainty of input data values does not impact
significantly on these encouraging outcomes in a one-way sen-
sitivity analysis. Sequelae due to PM were not included in the
analysis because usually they are rare in elderly people: the intro-
duction of this health status in the model could even increase the
favorable outcomes of the above assessment.
Since the cost-effectiveness profiles are immediately favorable
even in the 3-cohorts strategy, the continuation of a one-cohort
immunization program could be suggested after 5 y in order to
maintain benefits for the future.
A limitation of our study is the assumption that PCV13 is
effective against both IPD and CAP with the same efficacy
detected in the pediatric population with PCV7. An efficacy
study of PCV13 on CAP (CAPiTA Study) is ongoing in the
Netherlands, and results are expected by the end of 2013.
16
As a matter of fact, the extension of indication of the conjugate
pneumococcal vaccine to the adult population is based on the
comparative immunogenicity of PCV13 vs PPV23.
2,5
It is useful
to remind that also for the pediatric population, the substitution
of PCV7 with PCV13 was based on immunogenicity data,
2
also
because it was deemed ethically unacceptable to perform clinical
trials for new vaccines with a placebo arm in a situation of routine
administration of a very effective vaccine. For this reason, since
PCV13 effectiveness data in children are now corroborating the
Table3. Cost (Euro) per QALY in the sensitivity analysis
Univariate Sensitivity Analysis: Cost/Qaly
PCV13
1
cohort/
year
2
cohorts/
year
3
cohorts/
year
CAP due to S.pneumonia: 24.3% 27, 32 5 31,042 35,092
PCV13 vaccine efficacy: -10% 19,348 21,974 25,199
CAP, BPP, PM incidence: -10% 19,002 21,581 24,748
Vaccinated by GP: 50% 17,58 8 19,974 22,781
Base case scenario 16,987 19,289 22,109
PCV13 vaccination coverage: 50% 16,987 19,289 22,109
Hopitalized CAP cost: 3,286.82 Euro/case 16,802 19,074 21,869
Vaccine delivery cost/dose: 6574 y: 2 euro;
> 74 y: 1 euro
16,595 18,843 21,671
PCV13+PPV23
1
cohort/
year
2
cohorts/
year
3
cohorts/
year
CAP due to S.pneumonia: 24.3% 34,229 38,939 43,729
PCV13 vaccine efficacy: -10% 24,402 27,755 31,643
CAP, BPP, PM incidence: -10% 24,006 27, 30 4 31,141
Vaccinated by GP: 50% 22,478 25,565 28,962
Base case scenario 21,493 24,443 27, 86 6
PCV13 vaccination coverage: 50%
PPV23 vaccination coverage: 40%
21,315 24,239 27, 638
Hopitalized CAP cost: 3,286.82 Euro/case 21,310 24,230 27,628
Vaccine delivery cost/dose: 6574 y: 2 euro;
> 74 y: 1 euro
20,851 23,710 27,150
PCV13 vaccination coverage: 50%
PPV23 vaccination coverage: 30%
20,240 23,010 26,268
Multivariate Sensitivity Analysis: Cost/Qaly
PCV13
1
cohort/
year
2
cohorts/
year
3
cohorts/
year
• CAP due to S.pneumonia: 24.3%
• PCV13 vaccine efficacy: -10%
• CAP, BPP, PM incidence: -10%
• Vaccinated by GP: 50%
35,803 40,684 45,813
Base case scenario 16,987 19,289 22,109
• PCV13 vaccination coverage: 50%
• Hopitalized CAP cost: 3.286,82 Euro/case
• Vaccine delivery cost/dose: 6574 y: 2
euro; > 74 y: 1 euro
16,409 18,628 21,431
PCV13 + PPV23
1
cohort/
year
2
cohorts/
year
3
cohorts/
year
• CAP due to S.pneumonia: 24.3%
• PCV13 vaccine efficacy: -10%
• CAP, BPP, PM incidence: -10%
• Vaccinated by GP: 50%
45,111 51,332 57, 306
Base case scenario 21,493 24,443 27, 86 6
• PCV13 vaccination coverage: 50%
• PPV23 vaccination coverage: 30%
• Hopitalized CAP cost: 3,286.82 Euro/case
• Vaccine delivery cost/dose: 6574 y: 2
euro; > 74 y: 1 euro
19,483 22,143 25,391
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assumption of its efficacy both against IPD and pneumonia,
17
it is reasonable to assume high efficacy against different pneu-
mococcal diseases based on the excellent immunogenicity data
provided by pre-licensure studies. Nevertheless, our assumptions
will need to be verified in the light of effectiveness data progres-
sively available in the next years.
Many economic studies demonstrated that PPV23 vaccina-
tion in the adult population was cost-effective, and in some cases
a cost-saving strategy for the prevention of IPD.
18
However, the
new PCV13 could replace the first PPV23 immunization in sub-
jects 65 y. The results of our study justify, even from the eco-
nomic point of view, the implementation of PCV13 vaccination
in the elderly, and confirm the cost-effectiveness of this preven-
tive intervention, already recently adopted in the schedule of two
Italian Regions (Puglia and Sicily).
In conclusion, the implementation of an age-based PCV13
immunization strategy of elderly people in Italy turned out to
be already economically justified in the NHS perspective in the
first 5 y of adoption. The program brings to an immediate favor-
able cost-effectiveness profile; further benefits can be expected
extending the study period, due to the additional prevented
pneumococcal disease cases.
Therefore, it is now time for health care decision maker to
take advantage of this newly available tool for the improvement
of health in the adult population.
Materials and Methods
Mathematical model. A population model was developed to
value the clinical/economic impact of an age-based adult pneu-
mococcal vaccination program with PCV13 in Italy during a 5-y
period. The impact of PCV13 vaccination program was com-
pared with a no-vaccination scenario because the current PPV23
coverage is very low and not homogenous throughout the coun-
try. The mathematical model was constructed using Microsoft
Excel 2010 (Microsoft Corporation, Redmond, WA).
Particularly, three possible age-based PCV13 vaccination
strategies were evaluated: immunization of 65 y-old subjects
(single-cohort strategy), simultaneous vaccination of people aged
65 and 70 y (double-cohort strategy) and, lastly, simultaneous
immunization of subjects aged 65, 70 and 75 y (triple-cohort
strategy). The immunization program was assumed to last 5 y.
Consequently, the 3 strategies (1, 2 or 3 age-cohorts) imply the
overall immunization of 5, 10 and 15 cohorts, respectively. The
clinical and economic impacts of those vaccination scenarios
were evaluated on the entire Italian population aged 65 y. The
administration of one dose of PCV13, without booster doses, was
assumed.
19
The additional impact of administration of a PPV23
dose, one year after PCV13, was evaluated. Therefore, 4, 8 and
12 cohorts of subjects would receive both PCV13 and PPV23
immunization in the 5-y analysis period, respectively.
The model forecasted the clinical impact of PCV13 vaccina-
tion on the number of IPD: bacteraemic pneumococcal pneumo-
nia (BPP) and pneumococcal meningitis (PM) cases, and related
hospitalizations and deaths. The impact of vaccination on CAP
morbidity, hospitalizations and deaths was assumed considering
the rate of diseases due to S. pneumoniae. Figure 2 shows the
decision tree used in conjunction with the population model.
The outcomes of the model include annual number of clinical
cases, hospitalization and deaths related to CAP, BPP and PM
with and without vaccination program, and number of avoided
cases and rate of reduction due to immunization during the five
years of analysis.
Furthermore, the model calculates annual clinical costs and
the amount of net costs related to each immunization scenario.
The main outcome measures were life-years gained (LYGs),
quality-adjusted life-years (QALYs) and incremental cost-effec-
tiveness ratios (ICERs).
The analysis was performed according to the perspective of
the NHS and did not take into account the direct non-medical
costs and indirect costs associated with the loss of productivity
due to S. pneumoniae diseases.
Figure2. Decision tree used in the analysis in conjunction with the population model.
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704 Human Vaccines & Immunotherapeutics Volume 9 Issue 3
Epidemiological/clinical data. This study was
performed on the resident population in Italy
on January 1, 2011, grouped by age, as reported
by the National Institute for Statistics (Istituto
Nazionale di Statistica, ISTAT).
20
Only popula-
tion aged 65 y was included in the study. After
the first year of implementation of immuniza-
tion strategies, the age groups 61 y were pro-
gressively involved in the vaccination offer when
subjects became 65-y old.
Incidence, hospitalization rates and case
fatality rates of CAP were obtained by Viegi
et al.
21
The overall rate of CAP due to S. pneu-
moniae was calculated to be 39.8%,
22
assuming
that such percentage is the same for hospitalized
and non-hospitalized CAP cases.
Incidence and case fatality rates of BPP and
PM by age were derived from a cost-effective-
ness Italian study on PPV23 immunization in
elderly people.
23
Sequelae for meningitis were not included
in the analysis: usually they are rare in adult
subjects and the period of our analysis is short,
determining a very limited economic impact.
23,24
Lastly, although population models are used
for the evaluation of pneumococcal vaccination
strategies because they can include herd protec-
tion and serotype replacement effects,
6
never-
theless those two effects were not included in
the model, due to current lack of data in the
adult population.
Vaccine data. Vaccination coverage of the tar-
geted cohorts was supposed to be 60%, assum-
ing the same average national coverage for the
last annual influenza vaccination campaign
in Italy in elderly subjects. In addition, 73.5%
and 69.2% serotype coverage against pneumo-
nia and IPD, respectively, were assumed for
PCV13.
25
A PCV13 efficacy of 94% was assumed for
type-specific PM and 87.5% for pneumococcal
pneumonia (bacteremic and non-bacteremic) in
adult subjects, according to the data reported
in clinical trials in children immunized with
PCV7. While waiting for the availability of ef-
cacy data of PCV13 in adults, the comparative
immunogenicity data of PCV13 vs PPV23 in
elderly subjects made such assumption the most
reasonable. However, in order to account for a
possible lower effectiveness in adults compared
with children, a sensitivity analysis was per-
formed on those parameters.
2,16,26,27
Taking into account the supplemental
PPV23 vaccination, 50% of vaccination cov-
erage and 83.1% of serotype coverage were
assumed.
25
A steady value of efficacy against
Table4. Input data in the population model (base case scenario)
Clinical data Values Sources
Life expectancy at 65 years of age (years) 20
ISTAT website
35
CAP incidence > 64 y (per 1,000) 3.34
Viegi, 2006
21
CAP hopitalization rate (%) 31.8
Viegi, 2006
21
CAP case fatality rate (%) 6.0
Viegi, 2006
21
CAP due to S.pneumonae (%) 39.8
Bewick, 2012
23
BPP Incidence (per 100,000)
65–74 y: 7.8
75–84 y: 19.9
> 84 y: 52.4
Merito, 2007
23
PM Incidence (per 100,000)
65–74 y: 1.7
75–84 y: 1.9
> 84 y: 0.8
Merito, 2007
23
BPP case fatality rate (%)
65–74 y: 9.2
75–84 y: 12.6
> 84 y: 37.0
Merito, 2007
23
PM case fatality rate (%)
65–74 y: 18.5
75–84 y: 29. 4
> 84 y: 39.4
Merito, 2007
23
Vaccination data
PCV13 vaccination coverage (%) 60 as flu vaccination
PCV13 serotype coverage against pneumonia
(%)
73.5
Schito, 2011
25
PCV13 serotype coverage against IPD (%) 69.2
Schito, 2011
25
PCV13 efficacy against pneumonia (%) 87. 5
EM A , 2011
2
Black, 2000
26
Black, 2002
27
PCV13 efficacy against PM (%) 94
EM A , 2011
2
Black, 2000
26
Black, 2002
27
PPV23 vaccination coverage (%) 50 Assumption
PPV23 serotype coverage against IPD (%) 83.1
Schito, 2011
25
PPV23 efficacy against IPD (%) 70
Merito, 2007
23
Sisk, 2003
28
Ament, 2000
29
Smith, 2012
30
Cost data (Euro)
Cost discount rate (%) 3
Hopitalized CAP cost/case 2,680.85
Age.na.s. website
33
Non-hopitalized CAP cost/case 105
Potena, 2008
34
BPP cost/ case 4,068.40
Age.na.s. website
33
PM cost/case
65–74 y:
19,114.99
> 74 y:
15,474.08
Merito, 2007
23
PCV13 vaccine cost/dose 42.50
PPV23 vaccine cost/dose 16.00
Vaccine delivery cost by GP
65–74 y: 5.76
> 74 y: 2.88
Merito, 2007
23
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Table4. Input data in the population model (base case scenario) (continued)
Clinical data Values Sources
Subjects vaccinated with PCV13 by GP 0.25 Assumption
Subjects vaccinated with PPV23 by GP 0.25 Assumption
Quality-adjusted life-years weights
Average age-specific quality of life
65–70 y: 0.76
70–75 y: 0.74
75–80 y: 0.70
8085 y: 0.63
Sisk, 2003
28
IPD 0.2
Smith, 2012
30
n° hopitalization days:
34
Total weights: 0.02
CAP 0.2
Smith, 2012
30
n° hopitalization days:
11
Total weights: 0.01
Note: CAP: Community-acquired pneumonia; BPP: bacteremic pneumococcal pneumonia; PM:
pneumococcal meningitis; IPD: invasive pneumococcal disease.
IPD (70%) during the 5-y time of the program was applied.
23,28-30
Since efficacy of PPV23 on CAP has never been definitively
proven, no impact of this vaccine on non-bacteremic pneumonia
was assumed.
31,3 2
Economic data. The cost of hospitalized CAP cases and BPP
cases were obtained by the National Agency for Regional Health
Services (AGENAS) and were calculated as average of Regional
fare values in 2009.
33
An outpatient CAP case costs 105 Euro,
including antibiotic home treatment and specialist consultation
(without general practitioners examination cost, independently
paid by NHS).
34
All BPP and PM cases were assumed to be hos-
pitalized.
23
The cost of a PM case as reported by Merito et al. was
used in the analysis,
23
because of lack of official data.
In Italy, the current price (2012) paid by the NHS for a
PCV13 dose is 42.50 Euro, while it is approximately 16.00 Euro
for PPV23. It was assumed that all vaccines are administered by
health workers in the vaccination centers, except for 25% of the
target population, that was assumed to be immunized by general
practitioners. According to the current policies in Italy for the
annual influenza vaccination program, the payment of an incen-
tive to general practitioners for vaccine administration was fore-
seen in the model.
23
In order to calculate LYGs values, an average life expec-
tancy of 20 y was applied to 65 y-old subjects, as reported by
the National Institute of Statistics in 2011.
35
The QALYs gains
after the introduction of immunization strat-
egies were calculated applying the weights
referring to average age-specific quality of life
scores, CAP and IPD (the last two weights
are reported only for the average specific
number of hospitalization days: 11 and 34 d,
respectively).
28,30,36
A discount rate of 3% per year was applied
to medical costs for the treatment of pneu-
mococcal diseases cases, and to vaccination
costs (including vaccine and delivery costs).
However, no discounting was applied to life-
years gained.
All input data used in the mathematical
model in the base case scenario are shown in
Table 4.
Sensitivity analysis. The rate of CAP cases
due to S. pneumoniae was decreased from
39.8% to 24.3%, as reported in a meta-anal-
ysis study.
37
In addition, PCV13 and PPV23
vaccination coverages were simultaneously
lowered to 50% and 30%. The indirect effect
of the childhood vaccination program with PCV13 on elderly
subjects was not included in the analysis because of its recent and
not uniform implementation in the country, and to the evidence
that such indirect effect is only achievable with very high immu-
nization coverage. However, in order to take into account a pos-
sible partial herd effect, the baseline incidence rates of CAP, BPP
and PM were reduced by 10%. It was also speculated that 50%
of the elderly cohorts were immunized by general practitioners
(instead of 25%), with a related increment of delivery costs. Since
PCV13 efficacy in children was applied to elderly subjects, a 10%
reduction of vaccine efficacy against pneumonia and IPD was
tested. The cost per case of hospitalized CAP was varied to the
cost of therapy with levofloxacin, currently considered the most
relevant treatment, amounting to 3,286.82 Euro/case.
38
Lastly,
only 2 and 1 Euro of incentive for general practitioners (depend-
ing from the age group) were modeled instead of full price.
In addition, a multivariate analysis was performed in order to
explore the outcomes in terms of a “best” case and “worst” case
scenario by simultaneously using the most favorable and unfavor-
able parameters for the vaccination program.
Disclosure of Potential Conicts of Interest
One of the authors (S.B.) received a grant from Pfizer Italia to
support a part-time researcher position.
Page 7
©2013 Landes Bioscience. Do not distribute.
706 Human Vaccines & Immunotherapeutics Volume 9 Issue 3
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