03 Pneumococcal Ayabina 508

Summary of three economic analyses of the use of
20-valent pneumococcal conjugate vaccine (PCV20)
in children in the United States
Diepreye V. Ayabina
Division of Bacterial Diseases
CDC/NCIRDAdvisory Committee on Immunization Practices
June 22, 2023
Acknowledgements
•This presentation summarizes work conducted by three modeling teams
•Tulane -CDC team
•Charles Stoecker (Tulane University), Miwako Kobayashi (CDC), Andrew Leidner (CDC), Diepreye
Ayabina
•Pfizer team
•Mark Rozenbaum , Liping Huang, Alejandro Cane, Erica Chilson, Adriano Arguedas, Maria J. Tort,
Raymond Farkouh , Vincenza Snow
•Merck team
•Min Huang, Jessica Weaver, Elamin Elbasha
Views and opinions expressed in this presentation are the authors and do not necessarily represent the
views and opinions of the Centers for Disease Control and Prevention.2
Conflicts of interest statement
•Diepreye Ayabina: None.
•Tulane -CDC team: None.
•Pfizer team:
•Pfizer manufactures the PCV13 and PCV20 vaccines.
•Merck team:
•Merck manufactures the PCV15 and PPSV23 vaccines
3
Terminology
Abbreviation Full term/Meaning
AOM Acute otitis media
CMC Chronic medical conditions but not immunocompromised1
IC Immunocompromising conditions2
ICER Incremental cost -effectiveness ratio
IPD Invasive pneumococcal disease
PCV13 13-valent pneumococcal conjugate vaccine
PCV15 15-valent pneumococcal conjugate vaccine
PCV20 20-valent pneumococcal conjugate vaccine
PPSV23 Pneumococcal polysaccharide vaccine (23 serotypes)
QALYs Quality -adjusted life -years
1Includes chronic heart, lung, and liver diseases, diabetes.
2Includes chronic renal failure, nephrotic syndrome, congenital immunodeficiency, congenital or acquired asplenia, or splenic dysfunction, diseases associated with treatment of immunosuppressive drugs
or radiation therapy such as Hodgkin disease, leukemia, lymphoma, malignant neoplasm and solid organ transplant, HIV and sick le cell disease. 4
Outline
•Introduction
•Policy question #1: (Routine use of PCV20)
•Model description
•Estimated health outcomes and cost results
•Overview of cost -effectiveness results
•Model assumptions driving differences + sensitivity analysis
•Policy question #2: (Use of PCV20 in with underlying medical conditions that increase the risk of
pneumococcal disease)
•Estimated health outcomes and cost results
•Overview of cost -effectiveness results
•Model assumptions driving differences + sensitivity analysis
•Summary
5
Introduction
•This presentation describes three cost -effectiveness models that have been used to examine the costs and
benefits of including PCV20 as an option in the childhood immunization schedule developed.
•Tulane -CDC, Pfizer, and Merck
•Results of this presentation focus on routine use of PCV20 among <2 -year -olds, and among 2 -18-year -olds
with underlying conditions.
•Assessments of a supplemental PCV20 dose in children who completed the PCV series with PCV13 or PCV15 are not included
•All three reports went through the CDC economic review following the ACIP Guidance for Health Economics
Studies
•Completion of the economic review does not confer any explicit or implied approval of the model
6
Policy question 1
Routine use of PCV20 in children
Policy question #1
Should PCV 20berecommended as an option for pneumococcal
conjugate vaccination according tocurrently recommended dosing and
schedules, for children aged <2 years inthe United States?
𝐶𝑜𝑠𝑡𝑠𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝐶𝑜𝑠𝑡𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟= 𝑰𝒏𝒄𝒓𝒆𝒎𝒆𝒏𝒕𝒂𝒍𝒄𝒐𝒔𝒕 −𝒆𝒇𝒇𝒆𝒄𝒕𝒊𝒗𝒆𝒏𝒆𝒔𝒔𝒓𝒂𝒕𝒊𝒐(𝑰𝑪𝑬𝑹)𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟Intervention (dosing) Comparator (dosing)
PCV20 (3+1) PCV13 (3+1) /PCV15 (3+1)
8
Description of models
Policy question #1
Model characteristics Tulane -CDC Merck Pfizer
Cohort type Single birth cohort Single birth cohort Multi -cohort
Analytic model time frame 17 years 100 years 10 years
Include indirect effects Yes Yes ( only to IPD incidence) Yes
Base case perspective Societal Societal Societal
Currency year 2022 $ US 2022 $ US 2022 $ US
aVaccine price PCV13: $184
PCV15: $183
PCV20: $213PCV13: $192
PCV15: $189
PCV20: $213PCV13: $182
PCV15: $184
PCV20: $204
Other vaccine costs per dose Admin: $30; travel: $36 Admin: $19 Admin: $18
aAll three models used blended vaccine prices (vaccine price was weighted average of private and public market prices, weights wer e private and public market shares, which
varied across the models).
9
Health outcomes and cost resultsa
PCV20 vs PCV15, base case
PCV20 vs PCV15
Outcomes and cost Tulane -CDC Merck++Pfizer
Health outcomesIPD cases -360 -400 -30,000*
Pneumonia cases -13,000 -2,300 -1,400,000*
AOM cases -150,000 -201,000 -3,000,000*
Deaths -160 -28 -9,700*
QALYs 1,900 1,400 280,000
Costs ($ millions)Cost of disease + sequelae -210 -180 -12,000
Vaccine costs 440 330 2,100
Total cost 230 150 -10,000
10aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
All other values were discounted at 3%.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.
++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.
PCV20 vs PCV15
Outcomes and cost Tulane -CDC Merck++Pfizer
Health outcomesIPD cases -360 -400 -30,000*
Pneumonia cases -13,000 -2,300 -1,400,000*
AOM cases -150,000 -201,000 -3,000,000*
Deaths -160 -28 -9,700*
QALYs 1,900 1,400 280,000
Costs ($ millions)Cost of disease + sequelae -210 -180 -12,000
Vaccine costs 440 330 2,100
Total cost 230 150 -10,000
11aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
All other values were discounted at 3%.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15
++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost resultsa
PCV20 vs PCV15, base case
PCV20 vs PCV15
Outcomes and cost Tulane -CDC Merck++Pfizer
Health outcomesIPD cases -360 -400 -30,000*
Pneumonia cases -13,000 -2,300 -1,400,000*
AOM cases -150,000 -201,000 -3,000,000*
Deaths -160 -28 -9,700*
QALYs 1,900 1,400 280,000
Costs ($ millions)Cost of disease + sequelae -210 -180 -12,000
Vaccine costs 440 330 2,100
Total cost 230 150 -10,000
12aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
All other values were discounted at 3%.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.
++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost results
PCV20 vs PCV15, base casea
PCV20 vs PCV15
Outcomes and cost Tulane -CDC Merck++Pfizer
Health outcomesIPD cases -360 -400 -30,000*
Pneumonia cases -13,000 -2,300 -1,400,000*
AOM cases -150,000 -201,000 -3,000,000*
Deaths -160 -28 -9,700*
QALYs 1,900 1,400 280,000
Costs ($ millions)Cost of disease + sequelae -210 -180 -12,000
Vaccine costs 440 330 2,100
Total cost 230 150 -10,000
13aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
All other values were discounted at 3%.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.
++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost resultsa
PCV20 vs PCV15, base case
PCV20 vs PCV15
Outcomes and cost Tulane -CDC Merck++Pfizer
Health outcomesIPD cases -360 -400 -30,000*
Pneumonia cases -13,000 -2,300 -1,400,000*
AOM cases -150,000 -201,000 -3,000,000*
Deaths -160 -28 -9,700*
QALYs 1,900 1,400 280,000
Costs ($ millions)Cost of disease + sequelae -210 -180 -12,000
Vaccine costs 440 330 2,100
Total cost 230 150 -10,000
14aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
All other values were discounted at 3%.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15
++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost resultsa
PCV20 vs PCV15, base case
Model assumptions
*Indirect effects of pediatric PCV20 vaccination on adult pneumonia incidence
ModelDisease
outcomes
impacted by
indirect effectsDetails on the indirect effects methodologyAdjust for
PCV20 use
among 65+Data years
for indirect
effect on
pneumoniaApproximate
% of PCV20
only type
pneumoniaApproximate
reduction in
PCV20 -only
pneumonia
per cohort
Merck •IPD•Assume 8% reduction per year, with a max of
33% achieved in year 4 and maintained until the
end of the cohortNo NA (IPD considered only)
•Higher indirect effects as a result of PCV20 use would lead to PCV20 being more cost -effective when compared to other PCV vaccin es.
15
Model assumptions
*Indirect effects of pediatric PCV20 vaccination on adult pneumonia incidence
ModelDisease
outcomes
impacted by
indirect effectsDetails on the indirect effects methodologyAdjust for
PCV20 use
among 65+Data years
for indirect
effect on
pneumoniaApproximate
% of PCV20
only type
pneumoniaApproximate
reduction in
PCV20 -only
pneumonia
per cohort
Merck •IPD•Assume 8% reduction per year, with a max of
33% achieved in year 4 and maintained until the
end of the cohortNo NA (IPD considered only)
Tulane -
CDC•IPD
•Pneumonia
•AOM•Based on regression model estimates
•Estimated impact per vaccinated cohort
•Indirect effect benefit attributed to birth cohort
of children who receive PCV20Yes 2013 -2014a 0.6 to 2.4% 3.2%
Pfizer•IPD
•Pneumonia
•AOM•Based on observed reduction in all -cause
pneumonia Percentage of PCV20 type disease
Gradual increase in indirect effect over 10 yearsYes2008/2009 to
2018aGreater than
1 to 7%0.5 to 3.4%b
*Higher indirect effects as a result of PCV20 use would lead to PCV20 being more cost effective when compared to other PCV vac cines. The Tulane -CDC  and Pfizer models both accounted for the direct protection in all
adults.
aThe Tulane -CDC model estimated a monthly reduction in disease due to indirect effects, using data from 2013 and the first half of 2 014 (Pilishvili 2018a; Pilishvili et al. 2018b). The Pfizer model used a total reduction in
disease from 2008/2009 to 2018 (Tong et al. 2018, Table 3).
b.These are approximations based on calculations by the presenting author, based on each cohort in the Pfizer model contributing to i ndirect effects for 5 years. 16
Model assumptions
*Indirect effects of pediatric PCV20 vaccination on adult pneumonia incidence
ModelDisease
outcomes
impacted by
indirect effectsDetails on the indirect effects methodologyAdjust for
PCV20 use
among 65+Data years
for indirect
effect on
pneumoniaApproximate
% of PCV20
only type
pneumoniaApproximate
reduction in
PCV20 -only
pneumonia
per cohort
Merck •IPD•Assume 8% reduction per year, with a max of
33% achieved in year 4 and maintained until the
end of the cohortNo NA (IPD considered only)
Tulane -
CDC•IPD
•Pneumonia
•AOM•Based on regression model estimates
•Estimated impact per vaccinated cohort
•Indirect effect benefit attributed to birth cohort
of children who receive PCV20Yes 2013 -2014a 0.6 to 2.4% 3.2%
Pfizer•IPD
•Pneumonia
•AOM•Based on observed reduction in all -cause
pneumonia Percentage of PCV20 type disease
Gradual increase in indirect effect over 10 yearsYes2008/2009 to
2018aGreater than
1 to 7%0.5 to 3.4%b
*Higher indirect effects as a result of PCV20 use would lead to PCV20 being more cost effective when compared to other PCV vac cines. The Tulane -CDC  and Pfizer models both accounted for the direct protection in all
adults.
aThe Tulane -CDC model estimated a monthly reduction in disease due to indirect effects, using data from 2013 and the first half o f 2014 (Pilishvili 2018a; Pilishvili et al. 2018b). The Pfizer model used a total reduction in
disease from 2008/2009 to 2018 (Tong et al. 2018, Table 3).
b.These are approximations based on calculations by the presenting author, based on each cohort in the Pfizer model contributing to i ndirect effects for 5 years. 17
Cost effectiveness results: base case
PCV20 vs PCV13
aCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.Intervention Comparator Model Cost per QALY gained
PCV20 PCV13 Tulane -CDC 57,000
MerckaCost -saving
PfizeraCost -saving
PCV20 PCV15Tulane -CDC 125,000
Merck 105,003
PfizeraCost -saving
18
Cost effectiveness results: base case
PCV20 vs PCV15
aCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.Intervention Comparator Model Cost per QALY gained
PCV20 PCV13 Tulane -CDC 57,000
MerckaCost -saving
PfizeraCost -saving
PCV20 PCV15Tulane -CDC 125,000
Merck 105,003
PfizeraCost -saving
19
Sensitivity analysis (Policy question #1)
Cost -effectiveness of routine vaccination with PCV20 for children
Intervention Comparison ModelCost per QALY gained
Base case Rangeb
PCV20 PCV13 Tulane -CDC 57,000 NA
Merck Cost -saving NA
Pfizer Cost -saving All cost -saving
PCV20 PCV15 Tulane -CDC 125,000 [31,000 210,000 ]
Merck 105,000 [8,000              dominateda]
Pfizer Cost -saving [Cost -saving     60,000 ]
aIn one scenario in the Merck model, PCV15 was cost -saving relative to PCV20 (or PCV20 was dominated by PCV15), this scenario as sumed re -emergence of IPD associated with certain
serotypes that PCV20 missed the trial primary endpoint.
b The ranges presented are obtained from the scenario analyses and probabilistic sensitivity analysis.
Sensitivity analysis (Policy question #1)
Cost -effectiveness of routine vaccination with PCV20 for children
Intervention Comparison ModelCost per QALY gained
Base case Rangeb
PCV20 PCV13 Tulane -CDC 57,000 NA
Merck Cost -saving NA
Pfizer Cost -saving All cost -saving
PCV20 PCV15 Tulane -CDC 125,000 [31,000 210,000 ]
Merck 105,000 [8,000              dominateda]
Pfizer Cost -saving [Cost -saving     60,000 ]
aIn one scenario in the Merck model, PCV15 was cost -saving relative to PCV20 (or PCV20 was dominated by PCV15), this scenario as sumed re -emergence of IPD associated with certain
serotypes that PCV20 missed the trial primary endpoint.
b The ranges presented are obtained from the scenario analyses and probabilistic sensitivity analysis.
Policy question 2
Use of PCV20 in children with underlying medical conditions that increase the risk of pneumococcal disease
Policy question #2
Should PCV20without PPSV23 berecommended as an option for pneumococcal vaccination
according tocurrently recommended dosing and schedules, for U.S. children 2 –18years with
underlying medical conditions that increase the risk ofpneumococcal disease (CMC/IC)?
•2.1. What isthe cost effectiveness ofPCV20 alone vsPCV13/ 15+PPSV 23series among CMC/IC?
•2.2. What isthe cost effectiveness ofadding PPSV 23toa PCV 20series among CMC/IC?
𝐶𝑜𝑠𝑡𝑠𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝐶𝑜𝑠𝑡𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟= 𝐼𝑛𝑐𝑟𝑒𝑚𝑒𝑛𝑡𝑎𝑙 𝑐𝑜𝑠𝑡 𝑒𝑓𝑓𝑒𝑐𝑡𝑖𝑣𝑒𝑛𝑒𝑠𝑠 𝑟𝑎𝑡𝑖𝑜(𝐼𝐶𝐸𝑅)𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟Comparator (dosing) Intervention (dosing) Population
PCV13/15(3+1) + PPSV23 (1) PCV20 (3+1) CMC
PCV13/15(3+1) + PPSV23 (1+1) PCV20 (3+1) IC
PCV20(3+1) + PPSV23 (1) PCV20 (3+1) CMC
PCV20(3+1) + PPSV23 (1+1) PCV20 (3+1) IC
23
Policy question 2.1
PCV20 alone vs PCV13/15+PPSV23 series among CMC/IC
Health outcomes and costs
PCV20 alone vs PCV15+PPSV23 in CMC, base case
Outcomes and costPCV20 vs PCV15 + PPSV23
Tulane -CDC Merck Pfizera
Health
outcomesIPD cases -26 -15 -5*
Pneumonia cases -780 -260 -1,100*
AOM cases -30,000 -28,000 -4,900*
Deaths -2 -1 -5*
QALYs 200 140 120
Costs
($ millions)Vaccine costs -1 7 5
Cost of disease + sequelae -32 -23 -18
Total cost -33 -16 -12
aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15+PPSV23.
a.The Pfizer model does not directly assess policy question 2 but compares the receipt of PCV20 with and without PPSV23 to the receipt of PPSV23 on six -year -
old children with a history of PCV13 vaccination.
Health outcomes and costs
PCV20 alone vs PCV15+PPSV23 in CMC, base case
Outcomes and costPCV20 vs PCV15 + PPSV23
Tulane -CDC Merck Pfizera
Health
outcomesIPD cases -26 -15 -5*
Pneumonia cases -780 -260 -1,100*
AOM cases -30,000 -28,000 -4,900*
Deaths -2 -1 -5*
QALYs 200 140 120
Costs
($ millions)Vaccine costs -1 7 5
Cost of disease + sequelae -32 -23 -18
Total cost -33 -16 -12
aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15+PPSV23.
a.The Pfizer model does not directly assess policy question 2 but compares the receipt of PCV20 with and without PPSV23 to the receipt of PPSV23 on six -year -old
children with a history of PCV13 vaccination.
Health outcomes and costs
PCV20 alone vs PCV15+PPSV23 in CMC, base case
Outcomes and costPCV20 vs PCV15 + PPSV23
Tulane -CDC Merck Pfizera
Health
outcomesIPD cases -26 -15 -5*
Pneumonia cases -780 -260 -1,100*
AOM cases -30,000 -28,000 -4,900*
Deaths -2 -1 -5*
QALYs 200 140 120
Costs
($ millions)Vaccine costs -1 7 5
Cost of disease + sequelae -32 -23 -18
Total cost -33 -16 -12
In these assessments,
all three models
estimate higher health
and lower total costsaThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15+PPSV23.
a.The Pfizer model does not directly assess policy question 2 but compares the receipt of PCV20 with and without PPSV23 to the receipt of PPSV23 on six -year -old
children with a history of PCV13 vaccination.
Cost -effectiveness results, policy question
base case
Risk group Intervention Comparator ModelCost per
QALY
CMCPCV20PCV13 + PPSV23 Tulane -CDC
&
Merck Cost -saving PCV15 +PPSV23
PCV13 +PCV20 PCV13 + PPSV23 Pfizera
ICPCV20PCV13 + PPSV23 +PPSV23 Tulane -CDC
&
Merck Cost -saving PCV15 + PPSV23 + PPSV23
PCV13 +PCV20 PCV13 + PPSV23 + PPSV23 Pfizera
aPfizer model had a different set of comparisons: in CMC: PCV13 (3+1) + PCV20 vs. PCV13 (3+1)+ PPSV23; in IC: PCV13 (3+1) + PCV20 vs. PCV13 (3+1)+ PPSV23 + PPSV23 ,because it started at age
6.6.28
Sensitivity analyses policy question #2.1
PCV20 alone vs PCV13/15+PPSV23
Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.
*Aside from the base case, no additional scenarios were conducted for this comparison.
aInthe scenarios where the Merck model assumed a re -emergence of IPD associated with certain serotypes that PCV20 missed the trial primary endpoint, PCV15 was found to be cost -saving relative to PCV20 (or
PCV20 was dominated by PCV15).
bPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6.Risk
groupIntervention Comparator ModelRanges including sensitivity
analyses ($/QALY)
CMCPCV20 PCV13 + PPSV23Tulane -CDC*Cost -saving
Merck*Cost -saving
PCV13 + PCV20 PCV13 + PPSV23 Pfizer Cost -savingb
ICPCV20 PCV13 + PPSV23 + PPSV23Tulane -CDC*Cost -saving
Merck Cost -saving
PCV13 + PCV20 PCV13 + PPSV23 + PPSV23 Pfizer Cost -savingb
CMC
PCV20PCV15 + PPSV23Tulane -CDC Cost -saving to $19,000
Merck Cost -saving to dominateda
IC PCV15 + PPSV23 + PPSV23Tulane -CDC Cost -saving
Merck Cost -saving to dominateda
29
Sensitivity analyses policy question #2.1
PCV20 alone vs PCV13/15+PPSV23
Risk
groupIntervention Comparator ModelRanges including sensitivity
analyses ($/QALY)
CMCPCV20 PCV13 + PPSV23Tulane -CDC*Cost -saving
Merck*Cost -saving
PCV13 + PCV20 PCV13 + PPSV23 Pfizer Cost -savingb
ICPCV20 PCV13 + PPSV23 + PPSV23Tulane -CDC*Cost -saving
Merck Cost -saving
PCV13 + PCV20 PCV13 + PPSV23 + PPSV23 Pfizer Cost -savingb
CMC
PCV20PCV15 + PPSV23Tulane -CDC Cost -saving to $19,000
Merck Cost -saving to dominateda
IC PCV15 + PPSV23 + PPSV23Tulane -CDC Cost -saving
Merck Cost -saving to dominateda
30Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.
*Aside from the base case, no additional scenarios were conducted for this comparison.
aInthe scenarios where the Merck model assumed a re -emergence of IPD associated with certain serotypes that PCV20 missed the trial primary endpoint, PCV15 was found to be cost -saving relative to PCV20 (or
PCV20 was dominated by PCV15).
bPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6.
Policy question 2.2
PCV20 +PPSV23 series vs PCV20 alone among CMC/IC
Risk
groupIntervention Comparator ModelCost per
QALY
CMCPCV20 + PPSV23 PCV20Tulane -CDC $4 million
Merck $1.9 milliona
PCV13 + PCV20 + PPSV23 PCV13+ PCV20 Pfizerb $6 million
ICPCV20 + PPSV23 +PPSV23 PCV20Tulane -CDC $690,000
Merck $204,000a
PCV13 + PCV20 + PPSV23 +
PPSV23PCV13 + PCV20 Pfizerb $535,000
aValues calculated by presenter using results in Merck technical report.
bPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6. 32Cost -effectiveness results, policy question #2.2
PCV20+ PPSV23 vs PCV20 alone, base case
Risk
groupIntervention Comparator ModelCost per
QALY
CMCPCV20 + PPSV23 PCV20Tulane -CDC $4 million
Merck $1.9 milliona
PCV13 + PCV20 + PPSV23 PCV13+ PCV20 Pfizerb $6 million
ICPCV20 + PPSV23 +PPSV23 PCV20Tulane -CDC $690,000
Merck $204,000a
PCV13 + PCV20 + PPSV23 +
PPSV23PCV13 + PCV20 Pfizerb $535,000
aValues calculated by presenter using results in Merck technical report.
bPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6. 33Cost -effectiveness results, policy question #2.2
PCV20+ PPSV23 vs PCV20 alone, base case
Summary
Summary
35Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.•Policy question #1
•Vaccination with PCV20 is expected to improve health outcomes
compared to PCV13 or PCV15.
•Compared to PCV13 ,the Pfizer and Merck models estimated
that PCV20 would be cost -saving, whereas the Tulane -CDC model
estimated a cost per QALY of $57,000.
•Compared to PCV15 , the Pfizer model estimated that PCV20
would be cost -saving, whereas the Tulane -CDC model and the
Merck model estimated a cost per QALY of just over $100,000.
Summary
36•Policy question #2.1
•Compared to PCV13/PCV15+PPSV23 series, PCV20 alone in CMC/IC
was estimated to be cost -saving in all but two scenarios investigated
•Policy question #2.2
•Compared to PCV20 alone , PCV20 +PPSV23 series in CM/IC was estimated to
cost between $204,000 to $7 million dollars for each QALY gained
Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.
Summary
37Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.
bAdditional details on these model inputs provided in supplemental slides.•Main differences across models appear to be related to indirect effects
•bOther important factors: model structure, Vaccine effectiveness, QALY
losses due to disease
Thank you!Contributors
•Miwako Kobayashi
•Andrew Leidner
Supplemental slides
39
References
1. Stoecker C, Hampton LM, Link -Gelles R, Messonnier ML, Zhou F, Moore MR. Cost -effectiveness of using 2 vs 3 primary doses of 13 -valent
pneumococcal conjugate vaccine. Pediatrics. 2013;132(2):e324 -e32.
2. Stoecker, Charles, Miwako Kobayashi, Almea Matanock, Bo -Hyun Cho, and Tamara Pilishvili. "Cost -effectiveness of continuing
pneumococcal conjugate vaccination at age 65 in the context of indirect effects from the childhood immunization program." Vaccine 38,
no. 7 (2020): 1770 -1777.
3. Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with pneumonia in the United States during
2008 –2014. BMC Health Services Research. 2018 Dec;18(1):1 -8.
4. Pfizer. CDC ABCs data (Data on File)
5. Stoecker, Charles, Lee M. Hampton, Ruth Link -Gelles , Mark L. Messonnier, Fangjun Zhou, and Matthew R. Moore. "Cost -effectiveness of
using 2 vs 3 primary doses of 13 -valent pneumococcal conjugate vaccine." Pediatrics 132, no. 2 (2013): e324 -e332.
6. Pilishvili T. 2018a. “Estimating PCV13 direct and indirect effects on IPD among adults ≥65 years”. Presented at the meeting o f the Advisory
Committee on Immunization Practices, February 22, 2018. Atlant a, Georgia.
7. Pilishvili T, Girke R, Xing W, Farley M, Schaffner W, Thomas A, Reingold A, Harrison L, Lynfield R, Zansky S, Petit S, Barnes M, Bareta J, Beal
B, Shang N, Whitney C. 2018b. “Changes in invasive pneumococcal disease (IPD) among adults following 6 year s of 13 -valent
pneumococcal conjugate vaccine use in the U.S. ” Presented at the International Symposium on Pneumococci and Pneumococcal Diseases,
2018. Melbourne, Australia .
8. Prasad, Namrata, Charles Stoecker, Wei Xing, Bo -Hyun Cho, Andrew J. Leidner, and Miwako Kobayashi. "Public health impact and cos t-
effectiveness of 15 -valent pneumococcal conjugate vaccine use among the pediatric population of the United States." Vaccine 41, no. 18
(2023): 2914 -2921.
Health outcomes and cost resultsa
PCV20 vs PCV15, base case
PCV20 vs PCV15 PCV20 vs PCV13
Outcomes and cost Tulane -CDC Merck++Pfizer
Health outcomesIPD cases -360 -400 -430*
Pneumonia cases -13,000 -2,300 -25,000*
AOM cases -150,000 -201,000 -238,000*
Total deaths -160 -28 -93*
QALYs 1,900 1,400 5,600
Costs ($ millions)Cost of disease + sequelae -210 -180 NA
Vaccine costs 440 330 NA
Total cost 230 150 NA
41aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model
*Outcomes not reported as discounted values.
All other values were discounted at 3%.
Negative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.
++Pfizer  scenario analyses with single cohort and no indirect effects applied, and comparison is between PCV20 and PCV13
Model assumptions: Selected base case assumptionsa
Policy question #1
Model input Tulane -CDC Merck Pfizer
Vaccine effectiveness •lower VE for ST3 and
ST19F across all
vaccines.
•the serotype specific
VEsin PCV20 were the
same as the serotype
specific VEs in PCV15
and PCV13 .•serotype specific VE
was lower in PCV20 for
six
serotypes (3,12F,1,4,2
3F,9V) than it was in
PCV15.•the serotype specific
VEsin PCV20 were the
same as the serotype
specific VEs in PCV15
and PCV13 .
QALY loss due to
hospitalized pneumonia in
adults0.0105 0.071 0.13
Model structure Single cohort (17 years) Single cohort (100 years) Multiple cohorts (10
years)
aFrom the review, in addition to indirect effects, these assumptions appear to be the important in terms of determining differences between model results for policy question #1.
For added context, a QALY losses of 0.0016, 0.071 and 0.130 could be considered as representing a 32 -day hospitalization 59 -day hospitalization, respectively, where 20% health -related quality
of life is experienced for the duration of hospitalization. 42
Description of models
Policy question #2
Model characteristics Tulane -CDC MerckaPfizer
Cohort type Single birth cohort Single birth cohort Single -cohort (6 -year -olds)
•~90 % have history of PCV13
Indirect effects Yes (vaccinated CMC/IC contribute
to indirect effect benefits)In scenarios only (not in base case) Yes (vaccinated CMC/IC experience
reduced incidence)b
Vaccine coverage PCV (3rddose): 94 %
PCV(4thdose): 82 %
cPPSV23(1stdose): 78 %
dPPSV23(2nddose): 64 %PCV (3+1): 93 %
PPSV23(1stdose): 64 %
PPSV23(2nddose): 53 %PCV20: 20%
PPSV23: 20%
eWeighted
vaccine price ($)PPSV23: 85 PPSV23: 91 PPSV23: 85
aThe Pfizer model does not directly assess policy question 2, but compares the receipt of PCV20 with and without PPSV23 to the rec eipt of PPSV23 on children with a history of PCV13 vaccination
bIncidence among 6+ year olds was reduced after year 2, assuming routine use of PCV20 would occur, so VPD burden declines from routine use.
cVaccine coverage of first PPSV23 dose is a percentage of those who got 4 doses of PCVs.
dCoverage of second PPSV23 dose is a percentage of those who got the first PPSV23 dose.
eAllthree models used blended vaccine prices (combined using private and public market prices share weights which varied across t hemodels). 43
Summary
44Policy QuestionBase case estimates ($/QALY)
*Range across all
models Tulane -CDC Merck Pfizer
1. PCV20 vs
PCV13/PCV1557,000 to 125,000 Cost -saving to 105,000 Cost -saving Cost -saving to
dominateda
2.1 PCV20 alone (in
CMC/IC)Cost -saving Cost -saving to
dominateda
2.2 PCV20+PPSV23 vs
PCV20 (in CMC/IC)690,000 to 4
million204,000 to 1.9 million 535,000 to 6 million 204,000 to 7 million
Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.
*The ranges presented are obtained from the scenario analyses and probabilistic sensitivity analyses across all models
aThe Merck model found PCV15 was cost -saving relative to PCV20 (or PCV20 was dominated by PCV15) in scenarios where they assumed a r esurgence of specific PCV20 -only serotype IPD
disease.
bAdditional details on these model inputs provided in supplemental slides.•Main differences across models appear to be related to indirect effects
•bOther important factors: model structure, Vaccine effectiveness, QALY losses due to disease

Summary: Summary of three economic analyses of the use of  20-valent pneumococcal conjugate vaccine (PCV20)  in children in the United States Diepreye V. Ayabina Division of Bacterial Diseases CDC/NCIRDAdvisory Committee on Immunization Practices  June 22, 2023 Acknowledgements •This presentation summarizes work conducted by three modeling teams •Tulane -CDC team •Charles Stoecker (Tulane University), Miwako Kobayashi (CDC), Andrew Leidner (CDC), Diepreye Ayabina •Pfizer team •Mark Rozenbaum , Liping…


04 Pneumococcal Kobayashi 508

Evidence to Recommendations Framework and Policy Options:
Use of 20 -valent Pneumococcal Conjugate Vaccine in U.S. Children
Miwako Kobayashi, MD, MPH
Pneumococcal Vaccines Work Group
Advisory Committee on Immunization Practices
June 22, 2023National Center for Immunization & Respiratory Diseases
PICO
QuestionShould PCV20 be recommended as an option for pneumococcal vaccination
for U.S. children?
Population All U.S. children aged <2 yearsU.S. children aged 2 –18 years with
underlying medical conditions
InterventionPCV20 according to currently
recommended dosing and
schedulesPCV20 (without PPSV23)
Comparison PCV13 or PCV15 according to currently recommended dosing and schedules
OutcomesVT-IPD, VT -pneumonia, VT -AOM, VT -pneumococcal deaths, serious adverse
events following vaccination
VT: vaccine -type, IPD: invasive pneumococcal disease, AOM: acute otitis media2
PICO
QuestionShould PCV20 be recommended as an option for pneumococcal vaccination
for U.S. children?
Population All U.S. children aged <2 yearsU.S. children aged 2 –18 years with
underlying medical conditions
InterventionPCV20 according to currently
recommended dosing and
schedulesPCV20 (without PPSV23)
Comparison PCV13 or PCV15 according to currently recommended dosing and schedules
OutcomesVT-IPD, VT -pneumonia, VT -AOM, VT -pneumococcal deaths, serious adverse
events following vaccination
VT: vaccine -type, IPD: invasive pneumococcal disease, AOM: acute otitis media3
PICO
QuestionShould PCV20 be recommended as an option for pneumococcal vaccination
for U.S. children?
Population All U.S. children aged <2 yearsU.S. children aged 2 –18 years with
underlying medical conditions
InterventionPCV20 according to currently
recommended dosing and
schedulesPCV20 (without PPSV23)
Comparison PCV13 or PCV15 according to currently recommended dosing and schedules
OutcomesVT-IPD, VT -pneumonia, VT -AOM, VT -pneumococcal deaths, serious adverse
events following vaccination
VT: vaccine -type, IPD: invasive pneumococcal disease, AOM: acute otitis media4
Risk group/Condition
Children without immunocompromising conditions
Chronic heart disease†
Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in
immunocompromising conditions)
Chronic liver disease
Chronic lung disease (including moderate persistent or severe persistent asthma)
Diabetes mellitus
Cerebrospinal fluid leak
Cochlear implant
Children with immunocompromising conditions
On maintenance dialysis or nephrotic syndrome
Congenital or acquired asplenia, or splenic dysfunction
Congenital or acquired immunodeficiency¶
Diseases and conditions treated with immunosuppressive drugs or radiation therapy**
HIV infection
Sickle cell disease or other hemoglobinopathies
Solid organ transplant
†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.
¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).
** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.5
Risk group/Condition
Children without immunocompromising conditions
Chronic heart disease†
Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in
immunocompromising conditions)
Chronic liver disease
Chronic lung disease (including moderate persistent or severe persistent asthma)
Diabetes mellitus
Cerebrospinal fluid leak
Cochlear implant
Children with immunocompromising conditions
On maintenance dialysis or nephrotic syndrome
Congenital or acquired asplenia, or splenic dysfunction
Congenital or acquired immunodeficiency¶
Diseases and conditions treated with immunosuppressive drugs or radiation therapy**
HIV infection
Sickle cell disease or other hemoglobinopathies
Solid organ transplant
†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.
¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).
** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.6
Risk group/Condition
Children without immunocompromising conditions
Chronic heart disease†
Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in
immunocompromising conditions)
Chronic liver disease
Chronic lung disease (including moderate persistent or severe persistent asthma)
Diabetes mellitus
Cerebrospinal fluid leak
Cochlear implant
Children with immunocompromising conditions
On maintenance dialysis or nephrotic syndrome
Congenital or acquired asplenia, or splenic dysfunction
Congenital or acquired immunodeficiency¶
Diseases and conditions treated with immunosuppressive drugs or radiation therapy**
HIV infection
Sickle cell disease or other hemoglobinopathies
Solid organ transplant
†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.
¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).
** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.7
Rationale for updating indications for risk -based
recommendations
▪Improve harmonization between pediatric and adult recommendations
▪Data supporting increased risk of pneumococcal disease in this population
•Increased pneumococcal pneumonia1or IPD1,2risk in children with
asthma without long -term oral corticosteroid use
•Increased risk of IPD in children with chronic kidney disease
(regardless of stage)2,3
•Increased pneumococcal pneumonia2or IPD2,4risk in children with
chronic liver disease
IPD=invasive pneumococcal disease
1. Talbot et al. NEJM 2005 . Long -term oral corticosteroid use of ≥120 days defined as high risk
2. Pelton et al. CID 2014. Long -term oral corticosteroid use of ≥30 days defined as severe asthma
3. Hjuler et al. Pediatrics 2008.
4. Van Hoek et al. Journal of Infection 2012
ValuesEvidence to Recommendations ( EtR) framework
EtRDomain Question
Public Health Problem •Is the problem of public health importance?
Benefits and Harms •How substantial are the desirable anticipated effects?
•How substantial are the undesirable anticipated effects?
•Do the desirable effects outweigh the undesirable effects?
•What is the overall certainty of this evidence for the critical outcomes?
•Does the target population feel the desirable effects are large relative
to the undesirable effects?
•
Equity •Is there important variability in how patients value the outcomes?
Acceptability •Is the intervention acceptable to key stakeholders?
Feasibility •Is the intervention feasible to implement?
Resource Use •Is the intervention a reasonable and efficient allocation of resources?
What would be the impact of the intervention on health equity?9
Evidence to Recommendations ( EtR) framework
EtRDomain Question
Public Health Problem •Is the problem of public health importance?
Benefits and Harms •How substantial are the desirable anticipated effects?
•How substantial are the undesirable anticipated effects?
•Do the desirable effects outweigh the undesirable effects?
•What is the overall certainty of this evidence for the critical outcomes?
Values •Does the target population feel the desirable effects are large relative
to the undesirable effects?
•Is there important variability in how patients value the outcomes?
Acceptability •Is the intervention acceptable to key stakeholders?
Feasibility •Is the intervention feasible to implement?
Resource Use •Is the intervention a reasonable and efficient allocation of resources?
Equity •What would be the impact of the intervention on health equity?10
EtRDomain: Public Health Problem
Pneumococcal disease epidemiology in children
•Use of PCVs (PCV7, PCV13) significantly decreased the incidence of
pneumococcal disease in U.S. children.
•Outpatient ARIs caused by pneumococcus, such as AOM, sinusitis, and
pneumonia, are common causes of outpatient visits and antibiotic prescribing.
•Estimated incidence of outpatient visits and antibiotic prescriptions
attributable to PCV20, non -PCV13 serotypes: 4–5 times PCV15, non -PCV13
•In 2018 –2019, the proportion of IPD caused by vaccine serotypes was:
•PCV20, non -PCV13: ~30% of IPD
•PCV15, non -PCV13: ~15% of IPD
•PPSV23, non -PCV20: 1 –5% of IPD
•Risk of pneumococcal disease remains high in children with underlying
conditions that increase the risk of pneumococcal disease.
AOM=acute otitis media; ARI= acute respiratory illness; IPD=invasive pneumococcal disease
Gierke. February 2023 ACIP meeting presentation
King. February 2023 ACIP meeting presentation12
Monthly IPD rates (per 100,000) among children aged
<5 years old, 2018 –2022
0.000.200.400.600.801.001.201.40
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec2018 2019 2020 2021 2022 *
IPD=invasive pneumococcal disease
CDC ABCs unpublished data. *2022 estimates are preliminar y13
Public Health Problem
Is pneumococcal disease of public health importance in U.S.
children?
□
□
□
□
□
□No
Probably no
Probably yes
Yes
Varies
Don’t know
14
EtRDomain: Benefits and Harms
Summary of evidence: Benefits, children <2 years
•Informed by 2 randomized controlled trials (Phase II and III)1,2
•Healthy children randomized to either PCV13 or PCV20
•PCVs given using 3+1 schedule
•Summary of findings
•PCV20 had numerically lower IgG geometric mean concentrations vs. PCV13
for the 13 shared serotypes
•Post dose 3 :
•PCV20 did not meet noninferiority criteria* vs. PCV13 for serotypes 1, 3, 4, 9V, 23F, and
12F*** for one of the outcomes
•Post dose 4 :
•PCV20 noninferior **to PCV13 for all 13 shared serotypes
•PCV20 noninferior to PCV13*** for all 7 additional serotypes
*Measured as lower bound of 2 -sided 95% CI for percent difference proportion of participants (PCV20 -PCV13) meeting IgG threshold value of >=0.35μg/mL for all serotypes except ≥
0.23 μg/mL, ≥ 0.10 μg/mL and ≥ 0.12μg/mL for serotypes 5, 6B and 19A respectively
**Measured as lower bound of 2 -sided 95% CI for IgG geometric mean concentration ratio (PCV20/PCV13) >0.5
***Compared with the serotype with lowest immune response among PCV13 serotypes except for serotype 3
1. Senders et al. PIDJ 2021
2. Pfizer unpublished data from B747101116
Summary of evidence: Safety, children <2 years
•Serious adverse events (SAEs) across 3 studies (dose 1 through 6 months after
dose 4)1-3:
•PCV20: 4.5% (101 of 2,232) vs PCV13: 3.7% (64 of 1,717)
•None were considered to be vaccine -related
1. Senders et al. PIDJ 2021
2. Pfizer B7471011, https://www.fda.gov/media/149987/download
3. Pfizer B7471013, https://www.fda.gov/media/149987/download17
Should PCV20 be recommended as an option for pneumococcal conjugate
vaccination according to currently recommended dosing and schedules, for U.S.
children aged <2 years?
Type Outcome ImportanceIncluded in
evidence profileCertainty of
evidence
BenefitsVT-IPD Critical Yes Moderate
VT-pneumonia Critical Yes Moderate
VT-AOM Critical Yes Moderate
VT-pneumococcal
deathsCritical Yes Moderate
HarmsSAEs following
vaccinationCritical Yes Moderate
AOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine -type18
Summary of evidence:
Benefits, children 2 –18 years with underlying conditions
•No studies conducted among children with underlying medical conditions
•Informed by 1 non -randomized trial (Phase III), no comparator
•Healthy children aged 15 months to 17 years received a dose of PCV20
•Children aged <5 years received ≥3 doses of PCV13
•Summary of findings
•PCV20 was immunogenic * for all 20 vaccine serotypes 1 month after
vaccination vs. pre-vaccination.
*Measured as IgG GMCs and GMFR and OPA GMFRs
Pfizer unpublished data from B747101419
Summary of evidence:
Safety, children 2 –18 years with underlying conditions
•Serious adverse events (SAEs) :
•PCV20: 0.6% (5/831)
•None were considered to be vaccine -related
Pfizer unpublished data from B747101420
Should PCV20 without PPSV23 be recommended as an option for pneumococcal
vaccination for U.S. children aged 2– 18 years with underlying medical conditions that
increase the risk of pneumococcal disease?
Type Outcome ImportanceIncluded in evidence
profile Certainty of evidence
BenefitsVT-IPD Critical Yes Very Low
VT-pneumonia Critical Yes Very Low
VT-AOM Critical Yes Very Low
VT-pneumococcal
deathsCritical Yes Very Low
HarmsSAEs following
vaccinationCritical Yes Very Low
AOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine -type21
□
□
□
□
□
□Minimal
Small
Moderate
Large
Varies
Don’t knowBenefits and Harms
How substantial are the desirable anticipated effects?
▪Routine PCV20 use for children aged <2 years
▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions
•PCV20 provides the broadest serotype coverage among available
PCVs.
•Unknown how substantial the protection conferred from PCV20 will
be based on available data.
•No PCV20 data among children with underlying medical conditions .
22
Benefits and Harms
How substantial are the undesirable anticipated effects?
▪Routine PCV20 use for children aged <2 years
▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions
□
□Minimal
Small
□Moderate
□Large
□Varies
□Don’t know
23
Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
▪Routine PCV20 use for children aged <2 years
▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions
□
□
□Favors intervention*
Favors current recommendation
Favors both
□Favors neither
□Varies
□Don’t know*Intervention: PCV20 use
Comparison:
•Children <2 years: PCV13 or PCV15 use
•Children 2 –18 years with underlying
conditions: PPSV23 use after currently
recommended PCV (PCV13 or PCV15)
doses
24
EtRDomain: Equity
Summary of evidence
•Disparities in pneumococcal vaccine coverage by race/ethnicity, insurance coverage,
and poverty level exist1
•Nationally representative PPSV23 vaccine coverage data among children with
indications are limited2–5
•Range ~20 –60%, many reports from single institution
•Disparities in IPD rates by race and the percentage of census tract poverty remain6,7
•Most of the remaining disparities were due to serotypes not included in PCV20
1. ChildVaxView Interactive Child Vaccination Coverage | CDC
2. Reeves et al. Pediatric Blood & Cancer, 2018
3. Tran et al. Frontiers in Pediatrics, 2021
4. Mirza et al. The Ochsner Journal, 2022
5. Harris et al. Pediatrics, 2022
6. Farrar February 2022 ACIP meeting presentation
7. Kobayashi February 2023 ACIP meeting presentation26
Equity
What would be the impact of recommending PCV20 for U.S.
children on health equity?
□
□
□Reduced
Probably reduced
Probably no impact
□Probably increased
□Increased
□Varies
□Don’t know
27
Equity
What would be the impact of recommending PCV20 for U.S.
children aged <2 years on health equity?
Probably reduced:
•New interventions are likely to be accessible to wealthy communities, first
→VFC program mitigates inequities in access to recommended vaccines
Probably no impact:
•Remaining disparities in vaccine -type disease seem to be minimal
Probably increased:
•Post -PCV13 data showed that PCV13 reduced disparities in vaccine -type disease
VFC=Vaccines for Children28
Equity
What would be the impact of recommending PCV20 without
PPSV23 for U.S. children aged 2 –18 years with underlying
medical conditions on health equity?
Probably no impact:
•Risk-based recommendation is less likely to be equitable compared with routine
vaccine recommendations.
Probably increased:
•PCV20 use without PPSV23 could simplify the pneumococcal vaccine
recommendations and improve vaccine coverage.
29
EtRDomain: Values and Preferences
Values and Preferences
Criterion 1: Does the target population feel that the desirable
effects from vaccination are large relative toundesirable effects?
▪Routine PCV20 use for children aged <2 years
•Probably Yes
▪PCV20 without PPSV23 for children aged 2 –18 years with
underlying conditions
•Probably Yes/Yes
31
Values and Preferences
Criterion 2: Is there important uncertainty about, or variability
in, how much people value the main outcomes?
•Routine PCV20 use for children aged <2 years
•Probably important/not important uncertainty or
variability
•PCV20 without PPSV23 for children aged 2 –18 years with
underlying conditions
•Probably not important uncertainty or variability
32
Values and Preferences
Uncertainties:
▪No data assessing the public’s perception of PCV20
▪No data assessing efficacy/effectiveness of PCV20 against disease
▪Benefits from PCV20 use alone without PPSV23 for children with
underlying conditions are uncertain
Probably not important uncertainty or variability:
▪>90% vaccine coverage for ≥3 PCV doses in children by age 24 months1
▪Increased cases of invasive pneumococcal disease (late 2022): caregivers of
the child will likely value the use of PCV20
1.Hill et al. MMWR 2023.33
EtRDomain: Acceptability
Three healthcare provider surveys
▪Web -based surveys among providers who administer pneumococcal
vaccines to children
•1 by Pfizer (manufacturer of PCV13 and PCV20)1
•2 by Merck (manufacturer of PCV15 and PPSV23)2,3
1. Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers' Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Findings. 2023.
2. OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023.
3. Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023. 35
Key findings ( Pfizer survey )
Vaccine profiles of PCV15 and PCV20 shown, emphasizing IPD serotype coverage.
Children aged <2 years with incomplete series:
▪76% of providers responded that they would transition patients who started their PCV
series with either PCV13 or PCV15 to PCV20
•To provide protection against as many serotypes as possible ( 94% ).
Children with underlying conditions:
▪43% of providers responded that PCV20 alone without PPSV23 should be
recommended.
•Prefer/store only 1 vaccine instead of multiple vaccines ( 61% ).
•Prefer conjugated vaccines over unconjugated polysaccharide vaccines ( 48% ).
1. Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers' Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Findings. 2023.
36
Key findings ( Merck surveys )
▪Importance of pneumococcal vaccination
•>90% of providers believed that it is important to administer
pneumococcal vaccines to children aged <2 years.1
▪Important vaccine attributes
•≥90% of providers believed that it is important to have product -specific
data for immunocompromised or premature children.1
•Of the five vaccine attributes assessed for hypothetical vaccines, immune
response for the serotypes covered in PCV13 was given the highest
importance.2
1. Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023..
2. OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023.37
Acceptability
Is recommending PCV20 acceptable to key stakeholders?
▪Routine PCV20 use for children aged <2 years
•Yes
▪PCV20 without PPSV23 for children aged 2 –18 years with
underlying conditions
•Probably Yes/Yes
•Simplifies storage, less prone to vaccine administration errors
•Some providers may not feel comfortable recommending PCV20 alone without
PPSV23
38
EtRDomain: Resource Use
Summary of evidence
•Routine PCV20 use vs. PCV13 or PCV15 in children aged <2 years
•Base case ranged from cost -saving to $125,000 per QALY gained
•Differences across models related to indirect effects on adult disease
•PCV20 alone without PPSV23 use in children aged 2 –18 years with underlying
conditions
•PCV20 alone instead of PCV13/PCV15+PPSV23* was found to be cost -saving
in most model scenarios
•Addition of PPSV23 to PCV20 had high cost per QALY gained
•Greater than $1.9 million per QALY gained among CMC
•Between $200,000 to $690,000 per QALY gained among IC
CMC=chronic medical conditions, including chronic heart, lung, and liver disease, diabetes
IC=immunocompromising conditions, including chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV,
Hodgkin disease, leukemia, lymphoma, solid organ transplants, cochlear implants, CSF leaks, congenital or acquired asplenia, sic kle cell disease, or other hemoglobinopathies
QALY= quality -adjusted life -years
*CMC received 1 dose of PPSV23, IC received 2 doses of PPSV2340
□
□No
Probably no
□Probably yes
□Yes
□Varies
□Don’t knowResource Use
Is the option a reasonable and efficient allocation of resources?
▪Routine PCV20 use for children aged <2 years
▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions
Yes:
•Protects against more pneumococcal serotypes.
Minority opinion :
•Expensive vaccine.
•Uncertainties in the effectiveness remain.
•Onlyimmunogenicity data.
•No PCV20 data from children with underlying conditions.
•Challenging to interpret cost -effectiveness analyses findings that
use different methods and assumptions (routine PCV20 use).
•Sensitive to launch price.
41
EtRDomain: Feasibility
□
□No
Probably no
□Probably yes
□Yes
□Varies
□Don’t knowFeasibility
Is recommending PCV20 feasible to implement?
▪Routine PCV20 use for children aged <2 years
▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions
Routine PCV20 use for children aged <2 years:
•PCVs have been recommended for >20 years.
PCV20 without PPSV23 for children with underlying conditions:
•Simpler, streamlined recommendation.
•More feasible in general and are more likely to be followed in
clinical practice.
43
EtRDomains PCV20, <2 years (routine) PCV20, 2 –18 years old
Public Health Problem Yes
Benefits and Harms
a. Benefits Moderate
b. Harms Minimal
c. Benefit>Harm? Favors intervention/Favors both (split)
d. Overall certainty: effectiveness 2 (moderate) 4 (very low)
e. Overall certainty: safety 2 (moderate) 4 (very low)
Values
a. Desirable>Undesirable? Probably yes Probably yes/yes (split)
b. Uncertainty? Probably important uncertainty or
variability/Probably no important uncertainty or
variability (split)Probably no important uncertainty or variability
Acceptability Yes Probably yes/yes (split)
Resource Use Yes
Equity Probably increased (different opinions)
Feasibility YesSummary of Work Group Interpretation of the EtRDomains ( Updated )
44
Summary: Work Group Interpretations
Should PCV20 be recommended as an option for pneumococcal conjugate
vaccination according to currently recommended dosing and schedules for
U.S. children aged <2 years ?
Comparison: PCV13 or PCV15
Balance of
consequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most
settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most
settingsThe balance
between
desirable and
undesirable
consequences
is closely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most
settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most
settingsThere is
insufficient
evidence to
determine the
balance of
consequences
Summary: Work Group Interpretations
Should PCV20 be recommended as an option for pneumococcal conjugate
vaccination according to currently recommended dosing and schedules for
U.S. children aged <2 years ?
In support of recommending PCV20:
•Additional serotypes covered by PCV20 areexpected to prevent additional disease.
In support of recommending both PCV20 and PCV15*:
•We only have immunogenicity study data for both PCV20 and PCV15, clinical
implications are unknown.
•Range in cost -effectiveness analysis findings.
•Good to have options for PCVs, in case of challenges with/delays in access to PCV20.
*PCV13 expected to be removed from market after a transition period
Summary: Work Group Interpretations
Should PCV20 without PPSV23 be recommended as an option for children
aged 2–18 years with underlying medical conditions that increase the risk
of pneumococcal disease?
Comparison: PCV13 or PCV15 + PPSV23 according to current dosing
/schedule
Balance of
consequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most
settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most
settingsThe balance
between
desirable and
undesirable
consequences
is closely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most
settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most
settingsThere is
insufficient
evidence to
determine the
balance of
consequences
Summary: Work Group Interpretations
Should PCV20 without PPSV23 be recommended as an option for children
aged 2 to 18 years with underlying medical conditions that increase the
risk of pneumococcal disease?
In support of recommending PCV20 without PPSV23:
•Simplicity of PCV20 use without PPSV23, ease of vaccine storage.
•Immunologic advantages of PCVs over PPSV23.
•PCV20 provides the broadest serotype coverage among available PCVs.
In support of recommending BOTH PCV20 without PPSV23 AND PCV15* + PPSV23:
•No data on PCV20 use in children with underlying medical conditions.
•Harmonization with the updated adult pneumococcal vaccine recommendations
(October 2022 ACIP meeting).
*PCV13 expected to be removed from market after a transition period
Proposed Policy Options for a Vote
1. Routine PCV use for all children aged <24 months
Use of either PCV15 or PCV20 is recommended for all children aged 2 –23
months according to currently recommended PCV dosing and schedules.
50
Age at visit/
Health statusNo. of previous PCV13/PCV15/PCV20
doses received Recommended PCV15 /PCV20 regimen†
All children (healthy and those with risk conditions)
2–6 mos13 additional doses: 2 doses, 8 wks apart; last dose at age
12–15 mos
22 additional doses: 1 dose 8 wks after most recent dose;
last dose ≥8 wks later at age 12 –15 mos
3 1 additional dose at age 12 –15 mos
7–11 mos
1 or 2 (at age <7 mos) 2 additional doses: 1 dose 8 wksafter most recent dose;
last dose ≥8 wkslater at age 12 –15 mos
3 (at age <7 mos) 1 additional dose at age 12 –15 mos
1 (at age ≥7 mos)2 additional doses: 1 dose 8 wksafter most recent dose;
last dose ≥8 wkslater at age 12 –15 mos
2 (at age ≥7 mos) 1 additional dose at age 12 –15 mos
12–23 mos1 (at age <12 mos)2 additional doses: 1 dose ≥8 wksafter most recent dose;
last dose ≥8 wkslater
2 or 3 (at age <12 mos) 1 additional dose, ≥8 wks after most recent dose
1 (at age ≥12 mos) 1 additional dose, ≥8 wksafter most recent dose†
†Minimum interval between doses is 8 weeks except for children vaccinated at age <1 year, for whom minimum interval between do ses is 4 weeks.
51
2. Catch -up PCV doses for children aged 24 –71 months
with an incomplete PCV vaccination status
For healthy children aged 24 –59 months or through age 71 months
for children with any underlying condition that increases the risk of
pneumococcal disease (hereafter, risk condition)* with an incomplete
PCV vaccination status , use of either PCV15 or PCV20 according to
currently recommended PCV dosing and schedules isrecommended.
*Risk conditions include: cerebrospinal fluid leak; chronic heart disease ; chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in
immunocompromising conditions); chronic liver disease; chronic lung disease (including moderate persistent or severe persiste nt asthma ); cochlear implant; diabetes mellitus;
immunocompromising conditions ( on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired
immunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant ne oplasms, leukemias, lymphomas, Hodgkin disease, and
solid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).52
Risk group/Condition
Children without immunocompromising conditions
Chronic heart disease†
Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in
immunocompromising conditions)
Chronic liver disease
Chronic lung disease (including moderate persistent or severe persistent asthma)
Diabetes mellitus
Cerebrospinal fluid leak
Cochlear implant
Children with immunocompromising conditions
On maintenance dialysis or nephrotic syndrome
Congenital or acquired asplenia, or splenic dysfunction
Congenital or acquired immunodeficiency¶
Diseases and conditions treated with immunosuppressive drugs or radiation therapy**
HIV infection
Sickle cell disease or other hemoglobinopathies
Solid organ transplant
†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.
¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).
** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.53
Age at visit/
Health statusNo. of previous PCV13/PCV15/PCV20
doses received Recommended PCV15/ PCV20 regimen†
Healthy Children
24–59 mos No previous doses or any incomplete
schedule by 24 mos1 additional dose, ≥8 wks after most recent dose
5–18 yrs No previous doses or any incomplete
schedule by 24 mosNo additional dose
Children with risk conditions
24–71 mos No previous doses or any incomplete
schedule and <3 doses by age 24 mos2 doses: 1 dose ≥8 wks after most recent dose; last
dose ≥8 wks later
3 (all at age <12 mos) 1 additional dose, ≥8 wks after most recent dose
†Minimum interval between doses is 8 weeks except for children vaccinated at age <1 year, for whom minimum interval between do ses is 4 weeks.
54
3. Children aged 2 –18 years with any risk condition who have
completed their recommended PCV doses before age 6 years
For children aged 2 –18 years with any risk condition who have
received all recommended doses before age 6 years
•Using ≥1 dose of PCV20: No additional doses of any pneumococcal
vaccine are indicated. This recommendation may be updated as
additional data become available.
•Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using
previously recommended doses and schedule is recommended.
55
Children aged 2 –18 years with CMC, CSF leak, or cochlear implant
who have received all recommended PCV doses before age 6 years,
current recommendations
CMC=chronic medical conditions, including chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, whic h are included in
immunocompromising conditions), chronic heart disease, chronic liver disease, chronic lung disease (including moderate persis tent or severe persistent asthma),
diabetes mellitus; CSF=cerebrospinal fluidPPSV23Complete with
either PCV13/15≥8 weeks
56
Children aged 2 –18 years with CMC, CSF leak, or cochlear implant
who have received all recommended PCV doses before age 6 years,
proposed recommendations
CMC=chronic medical conditions, including chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, whic h are included in
immunocompromising conditions), chronic heart disease, chronic liver disease, chronic lung disease (including moderate persis tent or severe persistent asthma),
diabetes mellitus; CSF=cerebrospinal fluidPPSV23≥8 weeks Complete with
either PCV13/1 5PCV20Complete with
any PCV20 doseScenario 1PCV vaccination status
No additional doses
indicated
Option 1Scenario 2
≥8 weeksOption 2
57
Children with an immunocompromising condition aged 2 –18 years
who have completed PCV doses before age 6 years, current
recommendations
IC= immunocompromising conditionPPSV23 PPSV23
≥5 yearsComplete with
either PCV13/15 ≥8 weeks
58
Children with an immunocompromising condition aged 2 –18 years
who have completed PCV doses before age 6 years, proposed
recommendations
IC= immunocompromising conditionPPSV23≥8 weeks
PCV20Complete with
any PCV20 dose
PPSV23≥5 yearsScenario 1
PPSV23
≥8 weeksComplete with
either PCV13/15 ≥5 yearsPCV20
≥8 weeksOption 3Option 1
Option 2No additional doses
indicatedScenario 2PCV vaccination status
No additional doses
indicated
59
4. Children aged 6 –18 years with any risk condition
who have not received any dose of PCV
For children aged 6 –18 years with any risk condition who have not
received any dose of PCV13, PCV15, or PCV20, a single dose of PCV15
or PCV20 is recommended at least 8 weeks after the most recent dose
of pneumococcal vaccine. When PCV15 is used, it should be followed
by a dose of PPSV23 at least 8 weeks later if not previously given.
60
Current risk-based pneumococcal vaccine recommendations for PCV
unvaccinated children aged 6 –18 years with risk conditions
PCV13/15 recommendedPPSV23
RecommendedSingle PPSV23 revaccination
5 yrsafter first dose
Chronic heart disease Y
Chronic lung disease Y
Diabetes mellitus Y
Cerebrospinal fluid leak Y Y
Cochlear implant Y Y
Chronic renal failure or
nephrotic syndromeY Y Y
Congenital or acquired
asplenia, or splenic
dysfunctionY Y Y
Congenital or acquired
immunodeficiencyY Y Y
Diseases and conditions
treated with
immunosuppressive drugs or
radiation therapyY Y Y
HIV infection Y Y Y
Sickle cell disease or other
hemoglobinopathiesY Y Y
Solid organ transplant Y Y Y
Proposed risk-based pneumococcal vaccine recommendations for
PCV unvaccinated children aged 6 –18 years with risk conditions
PCV15/ 20recommended PPSV23 Recommended
Chronic heart disease Y Only if PCV15 used
Chronic kidney disease Y Only if PCV15 used
Chronic liver disease Y Only if PCV15 used
Chronic lung disease * Y Only if PCV15 used
Diabetes mellitus Y Only if PCV15 used
Cerebrospinal fluid leak Y Only if PCV15 used
Cochlear implant Y Only if PCV15 used
Maintenance dialysis or nephrotic syndrome Y Only if PCV15 used
Congenital or acquired asplenia, or splenic
dysfunctionY Only if PCV15 used
Congenital or acquired immunodeficiency Y Only if PCV15 used
Diseases and conditions treated with
immunosuppressive drugs or radiation
therapyY Only if PCV15 used
HIV infection Y Only if PCV15 used
Sickle cell disease or other
hemoglobinopathiesY Only if PCV15 used
Solid organ transplant Y Only if PCV15 used
*including moderate persistent or severe persistent asthma
Clinical Guidance
PCV13 use for children aged <6 years
•If only PCV13 is available when the child is scheduled to receive a PCV,
PCV13 may be given as previously recommended.
•If a child started the PCV series with PCV13, the child may complete the
series with PCV15 or PCV20 without giving additional doses. The PCV
series does not need to be restarted.
64
Children aged 6 –18 years with a risk condition who
have received PCV13 only
For children who have previously received PCV13only, either adose of
PCV20atleast 8weeks later orPPSV 23based onprevious dosing and
schedules isrecommended .
65
Children who have received hematopoietic stem cell
transplant (HSCT)
Children who received HSCT are recommended to receive three doses of PCV20 , 4 weeks
apart starting 3 –6 months after HSCT. A fourth PCV20 dose is recommended at least 6
months after the third PCV20 dose, or at least 12 months after HSCT, whichever is later.
HSCT recipients who have started their pneumococcal vaccine series with PCV13 or PCV15
may complete their 4 -dose pneumococcal vaccine series with PCV20 without giving extra
doses.
If PCV20 is not available, three doses of PCV15, followed by a dose of PPSV23 at least
12 months after HSCT may be given. For patients with chronic graft -versus -host disease
who are receiving PCV15, a fourth dose of PCV15 can be given in place of PPSV23 since
these children are less likely to respond to PPSV23.
A patient’s clinical team is best positioned to determine the appropriate timing of
vaccination .
Language aligned with clinical guidance for adults (October 2022 ACIP meeting)66
Acknowledgements
•ACIP and the Pneumococcal Vaccines Work Group
•CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Kristin Andrejko,
Lindsay Zielinski, Emma Accorsi, Adam Cohen, Alison Albert, Angela Jiles, Noele
Nelson, Diepreye Ayabina, Andrew Leidner, Pedro Moro, Elizabeth Velazquez,
Marc Fischer, Katie Hamilton, Noelle Sobotka, Rebecca Morgan, Doug Campos -
Outcalt
67
Summary of voting language:
No change in PCV doses or schedule
1. Use of either PCV15 or PCV20 is recommended for all children aged 2 –23
months according to currently recommended PCV dosing and schedules.
2. For healthy children aged 24 –59 months or through age 71 months for children
with any underlying condition that increases the risk of pneumococcal disease
(hereafter, risk condition)* with an incomplete PCV vaccination status , use of
either PCV15 or PCV20 according to currently recommended PCV dosing and
schedules isrecommended.
*Risk conditions include: cerebrospinal fluid leak; chronic heart disease ; chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in
immunocompromising conditions); chronic liver disease; chronic lung disease (including moderate persistent or severe persiste nt asthma ); cochlear implant; diabetes mellitus;
immunocompromising conditions ( on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired
immunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant ne oplasms, leukemias, lymphomas, Hodgkin disease, and
solid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).68
Summary of voting language:
Modifications to schedule
3. For children aged 2 –18 years with any risk condition who have received all
recommended doses before age 6 years
•Using ≥1 dose of PCV20: No additional doses of any pneumococcal vaccine are
indicated. This recommendation may be updated as additional data become available.
•Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using previously
recommended doses and schedule is recommended.
4. For children aged 6 –18 years with any risk condition who have not received any dose
of PCV13, PCV15, or PCV20, a single dose of PCV15 or PCV20 is recommended at least 8
weeks after the most recent dose of pneumococcal vaccination. When PCV15 is used, it
should be followed by a dose of PPSV23 at least 8 weeks later if not previously given.
69
Supplementary Slides
GRADE Summary of Evidence
Search strategy: PCV20 use in children
Database StrategyNo.
identifiedIncluded in
GRADE
Clinicaltrials.gov Inclusion: Relevant Phase 2, or 3 randomized controlled trials of PCV20
•Involved human subjects
•Reported primary data
•Included infants and children (age ≤18 years)
•Included data relevant to the efficacy or effectiveness or immunogenicity and safety
outcomes being measured
•Included data for the dosage and timing being recommended:
o3+1 series for infants starting the vaccine series as currently recommended
oCatch -up vaccine schedule for older infants and children who did not start the 3+1 series
in time
oUse of PCV20 to complete the PCV13 series
oUse of PCV20 in series with PPSV23 in older children with underlying conditions in series
with PPSV2312 3*
Pubmed
Medline“PCV20” or “20 -valent pneumococcal conjugate vaccine”
Included studies using the criteria listed above62 1
Additional
resourcesUnpublished and other relevant data by consulting with the vaccine manufacturer
2 3*
*Same trials. Unpublished data from these trials were obtained from pharmaceutical companies. 71
Included Studies: Routine PCV20 Use in Children Aged <2 years
Author, yearStudy
designIntervention Country Age Total
populationN
InterventionN
comparisonOutcomesFunding
source
Senders,
2021Phase II RCT
in healthy
full-term
infantsPCV20 @ 2, 4, 6,
and 12 months of
ageUS42–98
days of
age at
consent460 232 228Immuno -
genicity and
safetyPfizer
B7471011Phase III RCT
in healthy
full-term
infantsPCV20 @ 2, 4, 6,
and 12 –15
months of ageUS,
Puerto
Rico42–98
days of
age at
consent1998 1001 997Immuno -
genicity and
safetyPfizer
B7471013Phase III RCT
in healthy
infantsPCV20 @ 2, 4, 6,
and 12 –15
months of ageUS,
Puerto
Rico,
Canada,
Chile,
Argentin
a, EU42–98
days of
age at
consent1511 1000 551 Safety Pfizer
RCT=Randomized Controlled Trial72
GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years
Certainty assessment № of patients Results
Certainty Importance № of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsIntervention comparisonRelative
(95% CI)Absolute
(95% CI)
Vaccine effectiveness
21-2 RCTNot
seriousNot serious SeriousaNot serious Not serious 921-1022 910-989•PCV20 had numerically lower
immune responses compared
with PCV13 for most of the 13
shared serotypes.
•PCV20 did not meet one of the
noninferiority endpointsbfor
some serotypes (1, 3, 4, 9V, 23F,
and 12F) after dose 3.
•PCV20 noninferiorcto PCV13 for
all 13 shared serotypes after
dose 4.
•PCV20 noninferiorcto PCV13 for
all 7 additional serotypes after
dose 4.Moderate Critical
RCT=randomized clinical trial
a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.
b. Noninferiority for difference in percentages of participants meeting predefined IgG threshold value was defined as the low er bound of 2 -sided 95% confidence interval for percent difference (PCV20 -PCV13)> -10%. Additional 7 serotypes contained in
PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest percentage excluding serotype 3.
c. Noninferiority for GMC ratio was defined as the lower bound of 2 -sided 95% confidence interval of IgG GMC ratio (PCV20/PCV13) >0.5. Additional 7 serotypes contained in PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest
percentage excluding serotype 3.
References
1. Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20 -valent Pneumococcal Conjugate Vaccine in Health y Infants in the United States. Pediatr Infect Dis J. 2021 Oct
1;40(10):944 -951. doi: 10.1097/INF.0000000000003277.
2.B7471011. A Phase 3, Randomized, double -blind trial to evaluate the safety and immunogenicity of a 20 -valent pneumococcal conj ugate vaccine in healthy infants73
GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years
Certainty assessment № of patients Results
Certainty Importance № of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsIntervention ComparisonRelative
(95% CI)Absolute
(95% CI)
Serious Adverse Events (SAEs) following vaccination
21-3 RCT Not
seriousNot serious Not serious Seriousa Not serious 101/2232
(4.5%)64/1717
(3.7%)No vaccine -related
serious adverse events
reportedModerate Critical
RCT=randomized clinical trial
a. No vaccine -related serious adverse events reported
References
1.Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20 -valent Pneumococcal Conjugate
Vaccine in Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct 1;40(10):944 -951. doi: 10.1097/INF.0000000000003277.
2.B7471011. A Phase 3, Randomized, double -blind trial to evaluate the safety and immunogenicity of a 20 -valent pneumococcal conj ugate vaccine in healthy infants
3.B7471013. A Phase 3, Randomized, double -blind trial to evaluate the safety of a 20 -valent pneumococcal conjugate vaccine in he althy infants. Data limited to U.S. and Puerto Rico sites.
74
Included Study: PCV20 Use in Children Aged 2 –18 Years with Underlying
Medical Conditions
Author, year Study design Intervention Country Age Total
populationN
InterventionN
comparisonOutcomesFunding
source
B7471014Phase III
Clinical Trial
in healthy
children,
some
previously
vaccinatedSingle dose PCV20
@ 15m to <24m;
previous
vaccination ≥3
doses of PCV13
US15m
to
<24m209 209 N/A
Immuno -
genicity
and
safetyPfizerSingle dose PCV20
@ 2y to <5y;
previous
vaccination ≥3
doses of PCV132y to
<5y216 216 N/A
Single dose PCV20
@ 5y to <10y5y to
<10y201 201 N/A
Single dose PCV20
@ 10 to <18y10y
to
<18y205 205 N/A75
GRADE Summary of Findings: PCV20 Use in Children Aged 2 –18 Years
with Underlying Medical Conditions
Certainty assessment № of patients Results
Certainty Importance № of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsIntervention comparisonRelative
(95% CI)Absolute
(95% CI)
Vaccine effectiveness
11 Non -RCTVery
Serious
aNot
applicableVery
Seriousb,cNot
seriousNot serious 752-757 NoneIgG GMCs were higher 1 -
month post -PCV20 dose
compared to before
vaccination for 13/13 shared
serotypes and 7/7 additional
serotypes, for all age groupsVery Low Critical
RCT=randomized clinical trial
a. Study design is an open label non -randomized controlled trial with no comparator group. Downgraded for lack of randomization, la ck of blinding, and lack of a comparison group.
b. Study population did not include children with underlying conditions
c. This is an immunogenicity study and there are no correlates of protection for some critical outcomes considered
References
B7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age76
GRADE Summary of Findings: PCV20 use in Children Aged 2 –18
Years With Underlying Medical Conditions
Certainty assessment № of patients Results
Certainty Importance № of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsPCV20 InterventionRelative
(95% CI)Absolute
(95% CI)
Serious Adverse Events (SAEs) following vaccination
11 Non -RCTSerious
aNot
applicableSeriousb Seriousc Not serious5/831
(0.6%) No vaccine -related
SAEs reported Very Low Critical
RCT=randomized clinical trial
a. Study design is an open label non -randomized controlled trial with no comparator group
b. Study population did not include children with underlying conditions
c. No vaccine -related serious adverse events reported; relative risk crossing 1
Reference
B7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age
77

Summary: Evidence to Recommendations Framework and Policy Options:  Use of 20 -valent Pneumococcal Conjugate Vaccine in U.S. Children Miwako Kobayashi, MD, MPH Pneumococcal Vaccines Work Group Advisory Committee on Immunization Practices June 22, 2023National Center for Immunization & Respiratory Diseases PICO  QuestionShould PCV20 be recommended as an option for pneumococcal vaccination  for U.S. children? Population All U.S. children aged <2 yearsU.S. children aged 2 –18 years with  underlying…


01 Dengue Chen 508

Centers for Disease Control and Prevention
National Center for Emerging and Zoonotic Infectious Diseases
ACIP Dengue Vaccines Work Group
Wilbur Chen, MD, MSc
ACIP Member and Workgroup Chair
Advisory Committee on Immunization Practices
ACIP Meeting June 22, 2023

▪DENV -1, 2, 3, 4
•Lifelong DENV type -specific
immunity
•Short -term cross -immunity (~1 –2
years)
•A second dengue infection is the
most important risk factor for
severe dengue
▪Dengue is the most common
mosquito -borne virus globallyDengue Virus
Dengvaxia ™
and previous
dengue
infectionClinical trials found different outcomes after
Dengvaxia ™vaccination among children with and
without previous dengue infection.
•Children without previous dengue infection had a
higher risk for hospitalization and severe dengue if
they were vaccinated and then had a DENV infection.
•Children with previous dengue infection were
protected from hospitalization and severe dengue if
they were vaccinated with Dengvaxia ™.
Dengvaxia ™ACIP Recommendation June 2021
Three doses of Dengvaxia are indicated
for the prevention of dengue disease
caused by dengue virus serotypes 1, 2,
3, and 4 in people 9 –16 years old with:
•laboratory confirmation of previous
dengue virus infection
AND
•living in endemic areas.

Previous Presentations to ACIP on TAK -003
Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov2022 2023
•
••
•Takeda dengue
vaccine safety and
efficacy presentation
Workgroup summary
and interpretationDengue epidemiology
Review of Sanofi dengue
vaccine and ACIP
recommendation
Presentations Today
Introduction of policy questions for TAK -003
•Dr. Alfonso Hernandez, CDC, NCEZID, DVBD
Cost effectiveness analysis and health impacts of routine vaccination
with TAK -003 dengue vaccine in Puerto Rico
•Dr. Guido España , Notre Dame
Summary of two economic models for dengue vaccine TAK -003 use in
Puerto Rico
•Dr. RajReni Kaul, CDC
Partial evidence to recommendations framework for TAK -003
•Dr. Joshua Wong, CDC, NCEZID, DVBD
Future Presentations to ACIP on TAK -003
*Timeline subject to changeSep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov2022 2023
•
••
•
•
••
••
•
•Takeda dengue
vaccine safety and
efficacy presentation
Workgroup summary
and interpretationPolicy questions
Cost-effective (CE) analysis
(CDC/Notre Dame)
Comparison of CE models
Partial EtRDengue epidemiology
Review of Sanofi dengue
vaccine and ACIP
recommendation Full EtR*
Draft recommendation*
Vote*
ACIP Dengue Vaccines Work Group
ACIP Members
•Wilbur Chen (Chair)
•Kathy Poehling
•Beth Bell
•Veronica McNally
CDC Co -Leads
•Gabriela Paz -Bailey
•Laura Adams
Ex Officio Members
•Kaitlyn Morabito (NIH)
•Ralph LeBlanc (FDA)
•Ihid Carneiro Leao (FDA)
•Kirk Prutzman (FDA)•Srihari Seshadri (DOD)
•Liaison Representatives
•Elizabeth Barnett (AAP)
•Rob Schechter (AIM)
Consultants
•Edwin Asturias
•Robert Atmar
•Alan Barrett
•IrisCardona
•Anna Durbin
•Tony Marfin
•Kristen Pierce
•Anita ShetCDC Contributors
•Joshua Wong
•Nicole Medina
•Mimi Eckert
•Rachel Eidex
•Alfonso Hernandez
•Susan Hills
•Terri Hyde
•Mike McNeil
•Jorge Munoz
•Erin Staples
•Cindy Weinbaum
•Rita Helfand

Summary: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases ACIP Dengue Vaccines Work Group Wilbur Chen, MD, MSc ACIP Member and Workgroup Chair Advisory Committee on Immunization Practices ACIP Meeting June 22, 2023  ▪DENV -1, 2, 3, 4 •Lifelong DENV type -specific  immunity •Short -term cross -immunity (~1 –2  years) •A second dengue infection is the  most important risk factor for   severe dengue ▪Dengue is the most common  mosquito -borne virus…


02 Dengue Hernandez 508

Centers for Disease Control and Prevention
National Center for Emerging and Zoonotic Infectious Diseases
Introduction of Policy Questions for TAK -003
Alfonso Hernandez -Romieu, MD, MPH
ACIP June 22, 2023
Dengue Branch, CDC

We formulated PICO questions based on the
directness of data and risk -benefit differences.
*Persons aged 17 years were considered in this category but were not included in original immunobridging (18 –60 years) or
phase 3 trials (4 –16 years)•4–16 years: 57-month vaccine efficacy from a phase 3
randomized controlled trial
•17*–60 years: Non -inferiority of antibody titer ratios post -
vaccination (2 doses) compared to persons aged 4 –16 years
(i.e., immunobridging )
Result: Developed PICO questions by age -group
We formulated PICO questions based on the
directness of data and risk-benefit differences .
•No efficacy against hospitalizations for DENV -3 among
seronegative vaccine recipients compared to placebo (-87.9%;
95% CI: -573.4, 47.6%).
•Data insufficient to rule out an increased risk among
seronegative vaccine recipients.
Result: Developed PICO questions by serostatus
Hospitalization for DENV -3 and DENV -4 among
seronegative* children was low.
Placebo
n=1832Incidence
density/100
person -yearsTAK-003
n=3714Incidence
density/100
person -yearsVE (95% CI)
DENV -1 14 0.17 6 0.03 78.4% (43.9, 91.7%)
DENV -2 23 0.28 0 0.0 100% (NE, NE)
DENV -3 3 0.04 11 0.07–87.9% (–573.4, 47.6%)
DENV -4 1 0.01 0 0.0 100% (NE, NE)
*Seronegative refers to no serologic evidence of previous dengue infection before vaccination.
We formulated PICO questions based on the
directness of data and risk-benefit differences .
•No efficacy against hospitalizations for DENV -3 among
seronegative vaccine recipients compared to placebo (-87.9%;
95% CI: -573.4, 47.6%).
•Data insufficient to rule out an increased risk among
seronegative vaccine recipients.
Result: Developed PICO questions by serostatus
PICO questions include persons living in
dengue endemic areas only.
•Recommendations for travelers to dengue endemic areas will be
addressed by the work group after the October 2023 ACIP meeting.
•Travelers to endemic areas will require a separate evidence -to-
Recommendations ( EtR) framework including but not limited to:
•public health importance
•benefits and harms
•resource use
PICO Questions
1.Should two doses of TAK -003 be administered routinely to seropositive*
persons aged 4 –16 years living in dengue -endemic areas?
2.Should two doses of TAK -003 be administered routinely to seronegative
persons aged 4 –16 years living in dengue -endemic areas?
3.Should two doses of TAK -003 be administered routinely to seropositive*
persons aged 17 –60 years living in dengue -endemic areas?
4.Should two doses of TAK -003 be administered routinely to seronegative
persons aged 17 –60 years living in dengue -endemic areas?
*Recommendation for seropositive individuals only will require prevaccination screening for previous dengue virus infection.
Seropositive Seronegative
4–16 years
Children/Adolescents•Vaccine Efficacy (VE)
•Safety
•Cost -effectiveness (CE)•VE
•Safety
•CE
17–60 years
Adults•Immunobridging *
•Safety
•CE•Immunobridging
•Safety
•CEData elements used for each policy question
*Immunogenicity in seropositive adults inferred from data in seronegative adults.

Summary: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Introduction of Policy Questions for TAK -003 Alfonso Hernandez -Romieu, MD, MPH ACIP June 22, 2023 Dengue Branch, CDC  We formulated PICO questions based on the  directness of data and risk -benefit differences. *Persons aged 17 years were considered in this category but were not included in original immunobridging (18 –60 years) or     phase 3 trials (4 –16 years)•4–16 years: 57-month…


03 Dengue Espana 508

Economic analysis and health impacts of routine vaccination
with TAK- 003 dengue vaccine inSan Juan, Puerto Rico
Guido España, Manar Alkuzweny ,Alex Perkins
University ofNotre Dame
June 22nd,2023
Conflicts ofinterest & Disclosures
•GEand APhave previously received research funding from
GlaxoSmithKline tosupport unrelated research ondengue vaccine
development.
•APcurrently receives research funding and consulting fees from
Emergent Biosciences tosupport unrelated research on
chikungunya vaccine development.
•As of June 2023, GE is an employee of CDC. This work was
performed while working at the University of Notre Dame. The
findings and conclusions in this presentation are those of the
author(s) and do not necessarily represent the views of the CDC.
2
Abbreviation Full term/Meaning
VCD Virologically confirmed disease
VE Vaccine efficacy
DENV (e.g., DENV -3) Dengue virus (e.g., serotype 3 dengue virus)
HPV Human papillomavirus
PICO Policy question articulated as Population, Intervention,
Comparison, Outcomes
Additional hospitalizations Hospitalization induced by vaccine -enhanced disease
ICER Incremental cost -effectiveness ratio ($/QALY , $/hospitalization
averted)
QALY Quality adjusted life years
3Terminology
We modeled six scenarios to answer each of the
policy (PICO) questions.
•Age group scenarios:
•4 –16 years
•17 –60 years
•4 –60 years
•For each age group we modeled:
•Without required pre -vaccination screening (vaccinate
seropositives and seronegatives )
•With required pre -vaccination screening (vaccinate
seropositives only)
4
Outcomes of interest included benefits, harms, and
costs.
•Epidemiological outcomes:
•VCD* and hospitalizations averted
•Dengue hospitalizations among vaccinated seronegative
persons infected with DENV -3 and DENV -4.
•Health Outcomes:
•QALYs gained
•Economic outcomes:
•ICER ($/QALY)
•ICER ($/hospitalization averted)
*VCD refers to medically attended cases only 5
We calibrated an agent -based model to reproduce patterns
ofserotype circulation, force of infection, and age-specific
incidence.
•Wecreated asynthetic population torepresent demographic and
geographic characteristics ofSan Juan, Puerto Rico.
•Our model simulates individual daily activities ofhumans and
mosquitoes.
•Model calibrated using 30years ofhistorical dengue surveillance data
to reproduce observed force of infection and age -specific
incidence.
6
The serotype distribution simulated over 10 year time horizon of vaccination
was modeled on 30 (1986-2016) years of data from San Juan, Puerto Rico.
*Model based on 1,000 bootstraps with different proportion of serotypes in every simulation. Average reflects the mean propor tion of serotypes among
entire model. These estimates are preliminary and are subject to change.SerotypeAverage proportion in
model*
• DENV -1 14% (5% -25%)
• DENV -2 35% (17% -51%)
• DENV -3 29% (11% –46%)
• DENV -4 22% (9% -40%)
7
The estimated seroprevalence among persons 9 years of
age was approximately 40%.
•30% ofindividuals aged 5–9years were seropositive .
•People aged 20, 75% of people had ≥1 infection bytheend ofthe
calibration.Age group
8
Wesimulated the vaccine roll-out based onprevious
introduction ofHPV vaccine in the US*.
•Vaccine coverage increased gradually from 0% to ~40% in 10 years
and was distributed evenly across age ranges in the scenario.
•Wesimulated additional scenarios of2xand 0.5x thefinal coverage.
*https://www.cdc.gov/nchs/data/hus/2020 -2021/VaxTn.pdf 9
Vaccine efficacy and vaccine protection assumptions
10
Model and trial estimates of vaccine efficacy for VCD and
hospitalization among seropositive participants .
54100
70 686796
74100
020406080100
1 2 3 46385
43605680
5271
020406080100
1 2 3 4VCD HospitalizationVaccine efficacy
Takeda –ACIP WG presentation September13th –100% VE values are assumed. Biswal (Takeda). ACIP, February 17, 2023.11
Model and trial estimates of vaccine efficacy for VCD and
hospitalization among seronegative participants .
VCD Hospitalization
3096
30
-14588
-16
-106
-150-100-50050100
1 2 3 48599
-303978100
-88100
-150-100-50050100
1 2 3 4Vaccine efficacy
12
Takeda –ACIP WG presentation September 13th–100% VE values are assumed. Biswal (Takeda). ACIP, February 17, 2023.
Vaccine protection assumptions
•Protection varies foreach serotype (DENV 1 -4)and serostatus (seronegative
orseropositive).
•The duration of protection was estimated as
•VCD for seronegatives (13.1yrs) and for seropositives (17.4yrs)
•Hospitalization for seronegatives (19.3) and for seropositives (25.6).
•Equal level of protection against infection and disease given infection.
•In scenarios with pre -vaccination screening, the coverage of pre -vaccination
screening is the same as the vaccine rollout coverage (without screening). The
test has 80% sensitivity and 98% specificity for detecting previous dengue
infection.
•Wesimulated outcomes of VCD and hospitalizations over 10years in
scenarios with vaccination compared to scenarios without vaccination.
•We assumed that all individuals testing positive are vaccinated.
14
Epidemiological outcomes*: VCD and hospitalizations
averted (Benefits)
15*Results are preliminary and are subject to change.
No pre -vaccination screening increased the proportion
of total VCD averted compared to screening .
02468101214161820
1 2 3% of symptomatic VCD averted in the total
population
389
167
16*Results are preliminary and are subject to change.
No pre -vaccination screening increased the proportion of
total hospitalizations averted compared to screening .
02468101214161820
1 2 3% ofhospitalizations averted in the total
population
3 31315
1012
17*Results are preliminary and are subject to change.
Epidemiological outcomes: Additional hospitalizations
(Harms)
18
Outcomes: Additional hospitalizations (Harms)
•We used the ratio of averted hospitalizations to additional
hospitalizations as a relative measure of harm.
•Additional hospitalizations only occurred among seronegative persons
who received the vaccine and were infected with DENV -3 or DENV -4
post -vaccination.
19
Screening increased the ratio of averted to additional
hospitalizations compared to no pre-vaccination screening .
0102030405060708090100
1 2 3Ratio ofhospitalizations averted to
additional hospitalizations*
6:115:135:1
18:1102:1
69:1
*among seronegative persons who received the vaccine and were infected with DENV -3 post -vaccination.    Note: Results are prelim inary and are subject to change.
20
Economic outcomes*
21
Weestimated theIncremental Cost -Effectiveness
Ratio to determine cost -effectiveness
•Weestimated thequality -adjusted life-years (QALYs) gained with
routine vaccination using disability weights (Zeng et al. 2018)
•The unit cost perfully vaccinated individual was varied from 100
to 600 USD (330 USD baseline).Costintervention–Costnointervention= ICER
QALYintervention–QALYnointervention
*The cost per fully vaccinated individual was estimated as 150 USD per dose with an additional 15 USD for vaccine administrat ioncosts per dose. All
costs were estimated for the year 2022.
22
Economic outcomes* by scenario for a public
payer perspective, over 10 years, 3% discounting.
Age
groupPre-vaccination
screeningQALYs
gainedICER $ / QALY
gainedICER $ /
hospitalization
averted
4-16 Yes 17 181,918 16,800
4-16 No 35 254,751 46,813
17-60 Yes 89 396,574 48,986
17-60 No 118 314,597 39,886
4-60 Yes 106 384,830 48,305
4-60 No 134 326,412 45,495
23*Results are preliminary and are subject to change.
Summary
•Our model simulations show some benefits from vaccination in terms of
symptomatic cases and hospitalizations averted.
•These benefits depend ontheserostatus ofthevaccinees and the
circulating serotypes.
•Overall, pre-vaccination screening reduces thepotential negative
outcomes inseronegative individuals.
•ICERs per QALY gained and ICER per hospitalization averted were higher
when implementing pre -vaccination screening except in the 4 –16 age
group where screening was more cost -effective.
•Cost -effectiveness of the intervention depended on the
seroprevalence, which is lower for younger age groups.
24
Limitations
•Our model projections are not predictions on the serotype circulation or
theburden of disease.
•Our results on the benefits and cost -effectiveness of the intervention
depend on the circulation of specific serotypes during the projection
period.
•We are not including QALYs loss due to death in the cost -effectiveness
analysis.
24
Acknowledgements
This analysis isbased onprevious analyses described inthe
manuscript byEspaña etal.:“Model -based assessment ofpublic
health impact and cost-effectiveness ofdengue vaccination
following screening for prior exposure. PLOS NTDs 2019” (España
etal.,2019). The manuscript was prepared incollaboration with
other authors: Yutong Yao, Kathryn B.Anderson, Meagan C.
Fitzpatrick, David L.Smith, Amy C.Morrison, Annelies
Wilder-Smith, and Thomas W.Scott.
References I
Zeng, W.,Halasa -Rappel, Y.A.,Durand, L.,Coudeville, L.,&
Shepard, D.S.(2018). Impact ofanonfatal dengue episode
ondisability -adjusted lifeyears: Asystematic analysis. The
American Journal ofTropical Medicine and Hygiene ,99(6),
1458 –1465. https://doi.org/10.4269/ajtmh.18 -0309
Halasa ,Y.A.,Shepard, D.S.,&Zeng, W.(2012). Economic cost of
dengue inPuerto Rico. The American journal oftropical
medicine and hygiene ,86(5),745–752.
España ,G.,Yao, Y.,Anderson, K.B.,Fitzpatrick, M.C., Smith, D.
L.,Morrison, A.C.,Wilder -Smith, A.,Scott, T.W.,&
Perkins, T.A.(2019). Model -based assessment ofpublic
health impact and cost-effectiveness of dengue vaccination
following screening forprior exposure. PLOS Neglected
Tropical Diseases ,13(7),1–21.
https://doi.org/10.1371/journal.pntd.0007482

Summary: Economic analysis and health impacts of routine vaccination with TAK- 003 dengue vaccine inSan Juan, Puerto Rico Guido España, Manar Alkuzweny ,Alex Perkins University ofNotre Dame June 22nd,2023 Conflicts ofinterest & Disclosures •GEand APhave previously received research funding from  GlaxoSmithKline tosupport unrelated research ondengue vaccine development. •APcurrently receives research funding and consulting fees from Emergent Biosciences tosupport unrelated research on  chikungunya…


01 Chikungunya Chen 508

CHIKUNGUNYA VACCINES
ACIP Meeting
June 26, 2024
Wilbur Chen, MD, MS
Chair, ACIP Chikungunya Vaccines Work Group
•Chikungunya Vaccines Work Group formed in May 2022
•Developing policy options for ACIP’s consideration for use of chikungunya
vaccine among U.S. persons at risk of chikungunya
-Travelers
-Laboratory workers
-Residents of U.S. territories and states with risk of transmissionBackground
•October 2022
-Overview of chikungunya virus disease and vaccines
-Overview of live attenuated chikungunya vaccine
•February 2023
-Epidemiology of chikungunya globally and among U.S. travelers
-Sequelae of chikungunya
•June 2023
-Value of a vaccine to U.S. travelers
-Chikungunya virus infection among laboratory workers
•October 2023
-EtR for use of live attenuated chikungunya vaccine among U.S. travelers and
laboratory workersRecap of previous Work Group presentations to ACIP (1)
•February 2024
-Recommendations approved for use of live attenuated chikungunya vaccine
among U.S. travelers and laboratory workersRecap of previous Work Group presentations to ACIP (2)
•Update on chikungunya vaccines
•Epidemiology of chikungunya in U.S. territories and states
•Cost- effectiveness of use of live attenuated chikungunya vaccine among
adults living in U.S. territories
•Next steps for Work GroupOverview of today’s session
Chikungunya Vaccines Work Group members
ACIP ACIP Liaisons Invited Consultants ( cont )
Wilbur Chen, Univ Maryland Elizabeth Barnett, ISTM Margaret Ryan, DoD
Matthew Daley, Kaiser Permanente James Campbell, AAP Steven Schofield, CATMAT
Mary Pat Friedlander, AAFP David Shlim, Jackson Hole Travel & Trop Med
CDC Lead Saroj Rai, AIM Nestor Sosa, Uni New Mexico Hospital
Susan Hills, DVBD Sanet Torres, San Jorge Children & Women's Hospital
Invited Consultants Kirsten Vannice, Bill & Melinda Gates Foundation
Ex Officio Alan Barrett, Univ Texas Galveston Mary Wilson, Univ California San Francisco
Robin Levis, FDA Beth Bell, Univ Washington
Sixun Yang, FDA Carina Blackmore, Florida Dept Health
Lesley Dupuy (NIH) Alan Lam, DoD
Chikungunya Vaccines Work Group CDC participants
DVBD DGMH ISD
Erin Staples Kevin O’Laughlin Elisabeth Velazque z
Sarah Guagliardo
Ann Powers DHQP GRADE/ETR consultants
Laura Adams Michael McNeil Doug Campos -Outcalt
Joshua Wong Rebecca Morgan
GID
NCEZID Rebecca Casey ACIP Secretariat
Rita Helfand Jessica MacNeil, NCIRD
Leslie Lee, NCIRD

Summary: CHIKUNGUNYA VACCINES ACIP Meeting June 26, 2024 Wilbur Chen, MD, MS Chair, ACIP Chikungunya Vaccines Work Group •Chikungunya Vaccines Work Group formed in May 2022  •Developing policy options for ACIP’s consideration for use of chikungunya  vaccine among U.S. persons at risk of chikungunya  -Travelers -Laboratory workers -Residents of U.S. territories and states with risk of transmissionBackground •October 2022 -Overview of chikungunya virus disease and vaccines -Overview of live attenuated…


02 Chikungunya Hills 508

Update on chikungunya vaccinesNational Center for Emerging and Zoonotic Infectious Diseases
Susan Hills MBBS MTH
CDC Lead , Chikungunya Vaccines Work Group
Arboviral Diseases Branch
Division of Vector -Borne Diseases
Fort Collins, Colorado
ACIP Meeting, June 26, 2024
•Manufactured by Bavarian Nordic
•Submission of BLA to FDA completed on June 17, 2024
•Licensure possible first half of 2025
•Intended age group is adolescents and adults aged ≥12 years
•Single dose schedule Virus -like particle chikungunya vaccine
•Manufactured by Valneva as IXCHIQ
•Licensed November 9, 2023
•Age group currently adults ≥18 years
•Single dose schedule Live attenuated chikungunya vaccine

Summary: Update on chikungunya vaccinesNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP Meeting, June 26, 2024 •Manufactured by Bavarian Nordic •Submission of BLA to FDA completed on June 17, 2024 •Licensure possible first half of 2025 •Intended age group is adolescents and adults aged ≥12 years •Single dose schedule Virus -like particle…