Document text
Summary of three economic analyses on the use of
21-valent pneumococcal conjugate vaccine (PCV21)
among adults in the United States
Andrew J. Leidner, PhD
Applied Research, Implementation Science and Evaluation (ARISE) Branch
Immunization Services Division (ISD)
NCIRD
ACIP Meeting
June 27, 2024NCIRD/ISD/ARISE
The findings and conclusions in this report are those of the author and do not necessarily represent the views of the Centers for Disease Control
and Prevention.1
•This presentation summarizes work conducted by three modeling teams
-Tulane -CDC team
•Charles Stoecker (Tulane University), Yin Wang (Tulane University), Miwako Kobayashi (CDC), Andrew
Leidner (CDC), Bo-Hyun Cho (CDC), Cheryl Ward (CDC)
-Merck team
•Kwame Owusu -Edusei , Zinan Yi, Elamin Elbasha , Elmira Flem , Thomas Weiss, Heather Platt, Kristen
Feemster, Kelly Johnson, Ulrike Buchwald, Craig Roberts, Don Yin
-Pittsburgh team
•Shoroq Altawalbeh , Angela Wateska , Mary Patricia Nowalk , Chyongchiou Lin, Lee Harrison, William
Shaffner , Richard Zimmerman, Kenneth SmithAcknowledgements
2Disclaimer: 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.
•Andrew Leidner: None
•Tulane -CDC team: None
•Merck team:
-Merck manufactures the PCV21, PCV15 and PPSV23 vaccines
•Pittsburgh team:
-From the competing interest section of their articlea: Dr. Wateska has had a research grant from NIAID in the
past 3 years. Dr. Nowalk has had research grants from Merck & Co., Inc. and Sanofi Pasteur in the past 3 years.
Dr. Schaffner has had a research grant from CDC in the past 3 years. Dr. Zimmerman has had research grants
from NIH and Sanofi Pasteur in 3 years. Dr. Smith has had research grants from NIAID and Sanofi Pasteur in the
past 3 years.Conflicts of interest statement
3a. Altawalbeh , Shoroq M., et al. "Cost -effectiveness of an in -development adult -formulated 21 -valent pneumococcal conjugate vaccine in US adults aged 50 years or
older." Vaccine 42.12 (2024): 3024 -3032. Link.
Terminology
4Abbreviation Full term/Meaning
CER Cost -effectiveness ratio
CFR Case -fatality rate
CMC Chronic medical conditions but not immunocompromised
IC Immunocompromising conditions
ICER Incremental cost -effectiveness ratio
IPD Invasive pneumococcal disease
NBP Non -bacteremic pneumonia
PCV15 15-valent pneumococcal conjugate vaccine
PCV20 20-valent pneumococcal conjugate vaccine
PCV21 21-valent pneumococcal conjugate vaccine
PPSV23 23-valent pneumococcal polysaccharide vaccine
QALYs Quality -adjusted life -years
•Background on cost -effectiveness analysis
•Model overview
•Main results
•Model comparison
•SummaryOutline
5
•CEAs compare the costs and outcomes of two or more strategies by estimating a cost -effectiveness
ratio (CER)
-CER is an estimated cost per unit of health outcome gained
•Outcomes: averted cases, averted hospitalizations, quality -adjusted life years (QALYs)
•Cost per QALY gained ($/QALY)
-CERs always compare 2 potential strategies
•E.g., vaccination vs. no vaccination, vaccine schedule A vs. vaccine schedule B, new
vaccination vs. status quoWhat is cost -effectiveness analysis (CEA)?
6CostsVaccineA – CostsVaccineB Change in costs
= = $/Outcome
OutcomesVaccineA – OutcomesVaccineB Change in outcomes
What is cost -effectiveness analysis (CEA)?
7CostsVaccineA – CostsVaccineB Change in costs
= = $/Outcome
OutcomesVaccineA – OutcomesVaccineB Change in outcomes
Economic model inputs
Vaccine characteristics
Efficacy
Safety
Cost per dose
…
Disease burden inputs
Incidence rates
Health care costs
Mortality rates
…Economic model estimated outputs
Costs
Vaccination program costs
Disease -related costs
Health outcomes
Prevented episodes of disease
QALYs gainedEconomic
model
Interpreting a cost -effectiveness ratio
Change in costs
= $/Outcome
Change in outcomes
Quadrant II:
DominatedQuadrant I:
Higher costs &
higher health
Quadrant III:
Lower costs &
lower healthQuadrant IV:
Cost -savingBetter health outcomes
(Change in outcomes > 0)Worse health outcomes
(Change in outcomes < 0)Higher costs
(Change in costs > 0)
Lower costs
(Change in costs < 0)
VB
8 VB= VaccineB
•Background on cost -effectiveness analysis
•Model overview
•Main results
•Model comparison
•SummaryOutline
9
Model overview
10 a.In this presentation, all cost -effectiveness ratios that were reported in the Pittsburgh model have been adjusted to US$2023 (from US$2019) for consistency with the other models.Model characteristics Tulane -CDC Merck Pittsburgh
Cohort type Single cohort Multi -cohort Single cohort
Analytic model time frame Lifetime Lifetime Lifetime
Base case perspective Limited societal Societal Societal & healthcare sector
Currency year 2023 $ US 2023 $ US 2019 $ USa
Vaccine cost PCV20: $289
PCV21: $319PCV20: $261
PCV21: $287PCV20: $249
PCV21: $333
Other vaccine costs per doseAdmin: $30;
travel: $36Admin: $19 Admin: $24;
adverse events: $0.76
How many years following a PCV dose
until protections wanes to 0%15 years 15 years15 years for NBP
20 years for IPD
Circulating serotype protection ratio:
PCV21:PCV202.7 to 9.5
(vaccine -unique types)2.9 to 6.3
(vaccine -unique types)1.5 to 1.6
(all types)
Model overview, cont.
11Model characteristics Tulane -CDC Merck Pittsburgh
Include indirect effects from pediatric PCV20 use YesIn sensitivity
analysesIn sensitivity
analyses
Indirect effects magnitude, when included84% reduction
by year 633% reduction by
year 550% reduction
by year 1
Separately models disability sequalae, post -IPD NoaYes Yes
Separately models disability sequalae, post -NBP NoaNo Yes
Include age -adjusted incidence Yes Yes Yes
Include risk -stratified incidence groups General/CMC/IC General/CMC/ICBlack/Non -black &
General/Smoking/
CMC/IC
Case -fatality -rates (CFRs), inpatient pneumonia (NBP)
(%, among 50 -64 year olds)3 to 4b3b4 to 6b
Productivity loss for disease -related deaths adjusted by
employment status, varies by ageYes No No
a.In the Tulane -CDC model, inpatient disease burden assumptions includes a portion of the disease burden from disability sequalae, u p to 1 year for QALY loss and up to 6 months for costs.
b.For the Tulane -CDC and Merck model, NBP CFRs were based on National Inpatient Sample (i.e., hospital discharge) data, and in the Pi ttsburgh model NBP CFRs were assumed to be 50% of the rate of IPD CFRs.
Policy question 1: Currently recommended adults
Base case estimates ($/QALY)
12Intervention Comparator Tulane -CDC Merck Pittsburgh
Age-based vaccination
at 65 with PCV21Age-based vaccination
at 65 with PCV204,309
(Cost -saving to $18,599)a5,090
Cost -saving to
58,116b,cRisk-based vaccination
with PCV21Risk-based vaccination
with PCV20Cost -Saving
(Range was cost -saving)aCost -saving
a.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.
b.The Pittsburgh model assessed age -based and risk -based use in the same analysis, so strategies with age -based use at age 65 also in cluded risk -based use from age 50 to 64.
c.These ICER values were calculated by the CDC ACIP economic review team from costs and effectiveness values reported in the Pittsbur g model. High range value comes from healthcare sector perspective; low range
value comes from societal perspective.•PCV21 protection against circulating serotypes is greater, and PCV21 is modestly more
expensive than PCV20
Policy question 2: Age 50 -64
Base case estimates ($/QALY)
13Intervention Comparator Tulane -CDC Merck Pittsburgh
Age-based vaccination
at 50 and 65 with PCV21Age-based vaccination
at 65 with PCV21b269,643
($198,098 to $701,066)a105,303 to
256,318b2,713 to
114,645c
Age-based vaccination
at 50 and 65 with PCV20Age-based vaccination at 65
and risk -based vaccination at
50-64 with PCV20628,473 NAd36,854 to
149,269c
a.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.
b.The Merck model assessed PCV21 use at age 50 and 65 vs PCV21 use at age 65 among general risk (i.e., not CMC or IC) populations a nd PCV20 use among CMC/IC populations. High range value comes from a scenario
with indirect effects and without productivity loss from disease -induced death; low range value comes from a scenario without in direct effects and with productivity loss from disease -induced death.
c.These ICER values were calculated by the CDC ACIP economic review team from costs and effectiveness values reported in the Pittsbur g model. High range value comes from healthcare sector perspective; low range
value comes from societal perspective.
d. The Merck model did not assess lowering the age -based recommendation to 50 for the use of PCV20.•Higher ICERs than for the currently recommended group because younger ages have lower
disease burden
•PCV21 protection against circulating serotypes is greater
•PCV20 preventable disease burden is impacted by indirect effects
•Substantial variation in estimates within models, across models and across vaccines
Policy question 3: Age 19 -49
Base case estimates ($/QALY)
14Intervention Comparator Tulane -CDC Merck
Age-based vaccination
at 19 with PCV21 (Tulane -CDC); or
at 19 and 65 with PCV21 (Merck)bAge-based vaccination
at 50 with PCV21 (Tulane -CDC);
or at 65 with PCV20 (Merck)bDominated
(Range was dominated)a647,569b
Notes : The Pittsburgh model did not assess strategies for individuals younger than 50 years. Across all models, the use of PCV20 w as not directly assessed for 19 -50-year -olds.
a.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.
b.The Merck model intervention strategy was PCV21 at age 19 and 65 and the comparator was PCV20 at age 65.•Higher ICERs (or “dominated” interventions) than for currently recommended adult or age
50 strategies because younger ages have lower disease burden
Supplemental dose
Base case estimates ($/QALY)
15Intervention Comparator Tulane -CDC Merck
Supplemental dose with PCV21
among individuals who have
received PCV20 No supplemental dose
with PCV21206,191 to
442,010a274,844 to
512,266b
Note: The Pittsburgh model did not assess supplemental PCV21 dose.
a.Range depends on whether a person received PCV20 because of age -based or risk -based recommendation and the time since PCV20, where ri sk-based vaccinees with a longer duration since PCV20 had lower costs.
b.Range depends on age and time since PCV20; high value assumed age 65 general population (i.e., no CMC or IC) and older and 2 years since PCV20; low value assumed age 50 -64 CMC/IC population and 5 years since
PCV20.•Higher ICERs than for the currently recommended adult strategies because individuals
previously vaccinated with PCV20 have lower disease burden due to PCV20 vaccine
protection
•Variation in estimates due to duration between supplemental PCV21 dose and the previous
dose of PCV20, and due to differences in disease burden by age and risk group
•Background on cost -effectiveness analysis
•Model overview
•Main results
•Model comparison
•SummaryOutline
16
Sensitivity/scenario analyses
What if selected Pittsburgh model assumptions were more similar to the Tulane -CDC model?
17Base case
(Pittsburgh model)
Including PCV20
indirect effects
PCV20 indirect effects
and no disability
PCV20 indirect effects,
no disability, and lower
NBP CFR
Base case
(Tulane -CDC model)
- 50,000 100,000 150,000 200,000 250,000 300,000 350,000 400,000 450,000 500,000
Incremental cost -effectiveness ratio (ICER) ($/QALY)Policy Question 2: Age 50 -64
Cost -effectiveness estimates
In the Pittsburgh model results, lower ICERs are from the societal perspective, higher ICERs are from the health care sector perspective.
Policy question 2: Age 50 -64
Base case estimates ($/QALY)
18Intervention Comparator Tulane -CDC Merck Pittsburgh
Age-based vaccination
at 50 and 65 with PCV21Age-based vaccination
at 65 with PCV21b269,643
($198,098 to $701,066)a105,303 to
256,318b2,713 to
114,645c
Age-based vaccination
at 50 and 65 with PCV20Age-based vaccination at 65 and
risk-based vaccination at 50 -64
with PCV20628,473 NAd36,854 to
149,269c
a.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.
b.The Merck model assessed PCV21 use at age 50 and 65 vs PCV21 use at age 65 among general risk (i.e., no CMC or IC) populations an d PCV20 use among CMC/IC populations. High range value comes from a scenario
with indirect effects and without productivity loss from disease -induced death; low range value comes from a scenario without in direct effects and with productivity loss from disease -induced death.
c.These ICER values were calculated by the CDC ACIP economic review team from costs and effectiveness values reported in the Pittsbur g model. High range value comes from healthcare sector perspective; low range
value comes from societal perspective.
d. The Merck model did not assess lowering the age -based recommendation to 50 for the use of PCV20.•Comparison summary Tulane -CDC vs. Pittsburgh
-Not including PCV20 indirect effects, including long -term disability disease states, and higher pneumonia
CFR assumptions yield more favorable (i.e., lower) CERs
-Other factors include the magnitudes of indirect effect assumptions and productivity losses
•Limited data available on vaccine efficacy and duration of protection
•Uncertainties about several model inputs and assumptions
-Future epidemiology of pneumococcal serotypes that are not included in PCV21 (e.g., serotype 4, 19F)
-Indirect effects from pediatric PCV20 use
-Prevalence and severity of disability sequalae
-Vaccine price
•Merck model base case input for PCV21 cost per dose was $287, which has also been announced publicly as
the list pricea
•Potential challenges to vaccination implementation due to changing the pneumococcal
vaccine schedule were not includedLimitations
19a.US FDA approves Merck's pneumococcal vaccine for adults | Reuters
Summary of model findings
20Policy question
populations Strategy details Summary across available models
1. Currently
recommended
adultsAge-based PCV21 Cost -saving to $58,000 per QALY gained
Risk-based PCV21 Cost -saving in all three models
2. Ages 50 -64PCV21 $3,000 to $270,000 per QALY gained
PCV20 $37,000 to $630,000 per QALY gained
3. Ages 19 -49 PCV21 $650,000 per QALY gained to “Dominated”
Supplemental dose Supplemental dose with PCV21 $210,000 to $510,000 per QALY gained
•As modeled, most strategies improved health
-Age-based vaccination at 19 years instead of 50 years in the Tulane -CDC model did not improve health
•Several strategies were cost -saving
•Variability in estimates across models for age 50 and supplemental dose strategies
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY: 1 -888-232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Thank you for your attention and thank you to those that contributed to this presentation
21Tulane -CDC team
Charles Stoecker (Tulane University)
Yin Wang (Tulane University)
Miwako Kobayashi (CDC)
Andrew Leidner (CDC)
Bo-Hyun Cho (CDC)
Cheryl Ward (CDC)Merck team
Kwame Owusu -Edusei
Zinan Yi
Elamin Elbasha
Elmira Flem
Thomas Weiss
Heather Platt
Kristen Feemster
Kelly Johnson
Ulrike Buchwald
Craig Roberts
Don YinPittsburgh team
Shoroq Altawalbeh
Angela Wateska
Mary Patricia Nowalk
Chyongchiou Lin
Lee Harrison
William Shaffner
Richard Zimmerman
Kenneth SmithACIP economics review team
Austin Williams
Fangjun Zhou
Bo-Hyun Cho
Jamie Pike
Reni Kaul
Xiaoyu Dong