Document text
Summary of Work Group Interpretation of EtR and
Policy Options
PCV Use in Adults aged ≥50 years
October 23, 2024
Miwako Kobayashi, MD, MPHNational Center for Immunization and Respiratory Diseases
1
PICO for WG discussion through October 2024
CMC=chronic medical conditions (i.e., alcoholism; chronic heart disease, including congestive heart failure and cardiomyopath ies; chronic liver disease; chronic lung disease, including
chronic obstructive pulmonary disease, emphysema, and asthma; cigarette smoking; or diabetes mellitus); IC=immunocompromising condition(i.e., chronic renal failure, nephrotic
syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV infection, Hodgkin disease, leukemia, l ymp homa, multiple myeloma, solid organ transplant,
congenital or acquired asplenia, or sickle cell disease or other hemoglobinopathies). Those with a cerebrospinal fluid leak a nd a cochlear implant are also included among those with a
risk-based vaccine indication. Policy question: Should a single dose of pneumococcal conjugate vaccine (PCV) be recommended
for all PCV -naïve adults aged 50 –64 years?
Population PCV-naïve adults aged 50 –64 years in the United States
Intervention One dose of PCV15*, PCV20, or PCV21
*In series with PPSV23
Comparison Current risk -based vaccine recommendation (CMC or IC)
Outcomes Vaccine type (VT) -IPD, VT -non-bacteremic pneumococcal pneumonia, VT -
pneumococcal mortality, serious adverse events
Evidence to Recommendations ( EtR) framework
3EtR Domain Question
Public Health Problem • Is the problem of public health importance?
Equity • What would be the impact of the intervention on health equity?
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?
Resource Use • Is the intervention a reasonable and efficient allocation of resources?
Feasibility • Is the intervention feasible to implement?
Public Health Problem
Is pneumococcal disease of public health importance for adults aged 50 –64 years?
4
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age ≥65Invasive pneumococcal disease (IPD) incidence rates, by age
group, 2007 –2022
Source: CDC’s Active Bacterial Core surveillancePCV13:
children
5 Adapted from Gierke Feb 2024 ACIP meeting presentationPost -COVID
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age 50-64 Age ≥65Invasive pneumococcal disease (IPD) incidence rates, by age
group, 2007 –2022
Source: CDC’s Active Bacterial Core surveillancePCV13:
children
6 Adapted from Gierke Feb 2024 ACIP meeting presentationPost -COVID
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age ≥65Invasive pneumococcal disease (IPD) incidence rates, by age
group, 2007 –2022
SCDM: shared clinical decision -making
Source: CDC’s Active Bacterial Core surveillancePCV13: adults
65+PCV13:
children
7PCV13: adults 65+
based on SCDM
Adapted from Gierke Feb 2024 ACIP meeting presentationPost -COVID
IPD mortality rate* in adults aged ≥65 years has
become closer to that in adults aged 50 –64 years
ABCs Bact Facts Interactive Data Dashboard | ABCs | CDC . *deaths from IPD per 100,000 population 8
Adults aged 50 –64 years at increased risk of
pneumococcal disease
•Among adults aged 50 –64 years with pneumococcal disease (IPD1,
hospitalized pneumococcal pneumonia2), a high proportion (88%) of adults
had ≥1 condition with a risk -based pneumococcal vaccine indication (risk
condition)
1. CDC ABCs 2018 –2021 data
2. Self et al. PNEUMO study unpublished data 9
Is pneumococcal disease of public health importance?
•Success of pediatric PCV program
increased the relative burden of
pneumococcal disease in adults aged 50 –
64 years, especially in those with risk
conditions*.
•Additional Work Group comment:
-Should consider the absolute rate of disease
(rather than relative burden compared with
other age groups). IPD rates have come
down significantly compared with pre -PCV
era rates.
*Adults with certain underlying medical conditions or other risk factors 10□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know
Equity
What would be the impact of recommending PCV for all PCV -naïve adults
aged 50 –64 years on health equity?
11
About 32–54% of adults aged 50 –64 years have underlying
conditions with risk -based pneumococcal vaccine indication*
Source: NHIS 2020 data
*chronic heart disease, chronic lung disease, chronic liver disease, diabetes, smoking, alcoholism, weakened immune system du e to prescriptions, weakened immune system due to
health condition, solid cancer (not including non -melanoma skin cancer or unknown type of skin cancer) and blood cancer 120%10%20%30%40%50%60%70%80%90%100%
Age 50-64 years Age 65+ yearsHispanic
White, non-Hispanic
Black, non-Hispanic
Asian, non-Hispanic
Disparities in pneumococcal vaccine coverage by race/ethnicity exist
for both age -based and risk -based indications
Source: BRFSS 2022; AI/AN=American Indian and Alaska Native 130102030405060708090100
50-64 years, risk-based 65+ yearsPercentHispanic
White, non-Hispanic
Black, non-Hispanic
Asian, non-Hispanic
AI/AN, non-Hispanic
05101520253035
40-44 45-49 50-54 55-59 60-64 65+ 40-44 45-49 50-54 55-59 60-64 65+
Black Black Black Black Black Black Non
BlackNon
BlackNon
BlackNon
BlackNon
BlackNon
BlackIPD rates (any pneumococcal serotype) in Black adults peak
at a younger age compared with Non -Black adults
ABCs 2018 –2019 unpublished data 14IPD rate for adults aged ≥65 years across all
race/ethnicity (24/100,000)
Impact of hypothetical PCV20/PCV21 vaccination scenarios on
non-PCV13 -type IPD rates in adults aged ≥19 years
CDC ABCs 2014 –2019 unpublished data. 15
2 3
Vaccination Scenarios•For simplicity, assumes vaccine
protects against 100% of vaccine -
type disease
•Vaccine coverage is applied to
adults who developed non -
PCV13 -type IPD in 2014 –2019 (American Indian and Alaska Native)
Impact of hypothetical PCV20/PCV21 vaccination scenarios on
non-PCV13 -type IPD rates in adults aged ≥19 years
CDC ABCs 2014 –2019 unpublished data. 16
2 3
Vaccination Scenarios(American Indian and Alaska Native)
Vaccination Scenarios:
1.Current risk -based (19 –64 years)
and age -based (≥65 years)
recommendations with observed
vaccine coverage by race
• For simplicity, assumes vaccine protects
against 100% of vaccine -type disease
• Vaccine coverage is applied to adults who
developed non -PCV13 -type IPD in 2014 –2019 1 1Population
average
Impact of hypothetical PCV20/PCV21 vaccination scenarios on
non-PCV13 -type IPD rates in adults aged ≥19 years
CDC ABCs 2014 –2019 unpublished data. 17
2 3
Vaccination Scenarios(American Indian and Alaska Native)
1 1Vaccination Scenarios:
1.Current risk -based and age -based
recs with observed vaccine
coverage by race
2.Lower age -based recs to ≥50 years
using current coverage for adults
aged ≥65 years; risk -based for 19 –
49 years2 2
What would be the impact of recommending PCV for all PCV -
naïve adults aged 50 –64 years on health equity?
18□ Reduced
□ Probably reduced
□ Probably no impact
□ Probably increased
□ Increased
□ Varies
□ Don’t know
Work Group comments
•The intervention could help improve health equity by:
-Improving vaccine coverage for those with known or unknown risk conditions
-Providing protection at an earlier age when certain populations (e.g., Black
adults, AI adults) are already experiencing elevated disease rates
-Simplifying the recommendation, which could improve implementation across all
populations
•Acknowledged that the overall impact on health equity is complex and
would depend on how the recommendation is implemented and any
underlying disparities in healthcare access.
19
Benefits and Harms
20
Outcomes considered were specified in PICO
*Rated on a 1 to 9 scale, where 7 –9 are critical, 4 –6 are important, 1 –3 are of limited importance 21Outcome (Benefits) Importance* Data sources
VT-IPD Critical
PCV clinical trial data (immunogenicity)VT-non-bacteremic
pneumococcal pneumoniaCritical
VT-pneumococcal deaths Critical
Serious adverse events
(SAE)Critical PCV clinical trial data; post -licensure
safety data (PCV20)
Updated targeted literature search
•Previously conducted systematic review of literature and presented
summary of findings and GRADE for PCV151, PCV202, PCV213
•Updated literature search (August and September, 2024) based on current
PICO question
•6 PCV15 trials, 3 PCV20 trials, and 7 PCV21 trials included in the updated
review (list of studies available in supplemental slides)
1. Presented summary of literature search through February 18, 2021
2. Presented summary of literature search through March 31, 2022
3. Presented summary of literature search through October 17, 202322
PCV clinical trial data (immunogenicity)
Conclusions remain unchanged
•PCV15: Noninferior1 to PCV13 for all shared serotypes; had statistically significantly
greater response2 for non -PCV13 serotypes 22F and 33F vs. PCV13
•PCV20: Noninferior3 to PCV13 for all shared serotypes; noninferior3 to PPSV23 for
6/7 non -PCV13 serotypes (not met for serotype 8)
•PCV21: Noninferior4 to PCV20 for 10/10 shared serotypes; had statistically
significantly greater response5 for 10/11 PCV21 -unique serotypes (except serotype
15C)
1. Noninferiority defined as the lower bound of the 2 -sided 95% CI of the OPA GMT ratio (PCV15/PCV13) to be >0.5.
2. Statistically significantly greater response for unique serotypes (22F and 33F) defined as the lower bound of the 2 -sided 95% CI of the OPA GMT ratio (PCV15/PCV13) to be >2.0 and the lower bound of
the 2 -sided 95% CI of the differences (PCV15 -PCV13) between the proportions of participants with a ≥4 -fold rise to be >0.1 (or 1 0 percentage points)
3. Noninferiority for a serotype was declared if the lower bound of the 2 -sided 95% CI for the OPA GMT ratio (PCV20/comparator vacci ne) for that serotype was greater than 0.5 (2 -fold criterion).
4. Noninferiority for GMT ratio was defined as the lower bound of the 2 -sided 95% CI of the OPA GMT ratio [PCV21 / (Comparator Vacc ine)] to be >0.5.
5. Statistically significantly greater response for GMT ratio was defined as the lower bound of the 2 -sided 95% CI of the OPA GMT r atio [PCV21 / (Comparator Vaccine)] to be >2.0. Statistically significantly
greater response for difference in proportions of participants with a ≥4 -fold rise in serotype -specific OPA responses from basel ine to 30 days postvaccination was defined as the lower bound of the 2 -
sided 95% CI of the differences [PCV21 – (Comparator Vaccine)] between the proportions of participants with a ≥4 -fold rise from baseline to 30 days postvaccination to be >0.1. 23
1. How substantial are the desirable anticipated
effects* of PCV vaccination?
Intervention: Recommending PCV for all PCV -naïve adults aged 50 –64 years
Comparator: Risk-based recommendation for adults with CMC/IC
CMC: chronic medical conditions, IC=immunocompromising conditions 24□ Minimal
□ Small
□ Moderate
□ Large
□ Varies
□ Don’t know *Desirable anticipated effects for the following outcomes
as specified in the PICO:
Vaccine -type (VT) IPD, VT non -bacteremic pneumococcal
pneumonia, VT pneumococcal mortality
Certainty of evidence (February 2024 ACIP meeting):
Moderate
PCV clinical trial data (safety)
Conclusions remain unchanged
•No vaccine -related serious adverse events reported for PCV15 and PCV20
•Two vaccine -related serious adverse events reported among PCV21
recipients (previously presented)
-Bronchospasm (V116 -005): 50 -year -old female in the sequential group with
bronchospasm within 30 minutes after the 2nd vaccination (V116); duration 23
hours; resolved
-Injection site cellulitis (V116 -006): 67 -year -old female in Cohort 1 (prior PPSV23)
with injection site cellulitis on Day 6; duration 1.57 weeks; resolved
25
Post -licensure PCV20 safety data
What we presented during the February 2024 ACIP meeting
•October 2021 –December 2023: 1,976 VAERS reports after PCV20 in adults*
•Most reports were classified as non -serious
•Data mining alert for disproportional reporting of Guillain -Barré Syndrome (GBS)
after PCV20 vaccine
•11 reports for GBS after PCV20 vaccine, verified by chart review
•The reporting rate for GBS after PCV20 vaccine was 0.5 cases per million doses distributed
•FDA also presented preliminary FDA -CMS partnership data at the meeting
•Near real -time monitoring in Medicare beneficiaries aged ≥65 years had not identified a
safety signal for GBS
*adults defined as individuals aged ≥19 years 26
Post -licensure PCV20 safety data
Updated data
•October 2021 –August 2024 : 2,767 VAERS reports after PCV20 in adults*
•18 reports for Guillain -Barré Syndrome (GBS) after PCV20 vaccine, verified by chart
review
•The reporting rate for GBS after PCV20 vaccine was 0.7 cases per million doses
distributed
•Updated data findings from FDA-CMS partnership ( data through May 31, 2024 )
•A statistically significant signal (IRR>1†) for GBS following PCV20 vaccination in Medicare
beneficiaries aged ≥65 years identified when using the primary GBS definition
•GBS events were not chart confirmed (based on claims)
•Findings were not statistically significant when using a different GBS definition or
adjusting for positive predictive value
•Incidence was low (<10 GBS cases per 100K person -years), resulting in wide
credible intervals
*adults defined as individuals aged ≥19 years
†Bayesian Poisson Regression was used to estimate the posterior distribution of incidence rate ratio (IRR) between pre -specified risk and comparison windows 27
Summary: Post -licensure PCV20 safety data
•Potential Guillain -Barré Syndrome (GBS) signal for PCV20 in VAERS
•GBS signal in Medicare sequential monitoring for primary definition, but
not for alternate definition or when adjusted for positive predictive value
•Significant uncertainty because of the small number of GBS cases
observed
•CDC and FDA will continue to monitor post -licensure PCV safety
28
2. How substantial are the undesirable anticipated
effects* of PCV vaccination?
Intervention: Recommending PCV for all PCV -naïve adults aged 50 –64 years
Comparator: Risk-based recommendation for adults with CMC/IC
CMC: chronic medical conditions, IC=immunocompromising conditions 29□ Minimal
□ Small
□ Moderate
□ Large
□ Varies
□ Don’t know *Desirable unanticipated effects for the following
outcome as specified in the PICO: Serious adverse events
Certainty of evidence (February 2024 ACIP meeting):
Moderate
3. Do the desirable effects of PCV vaccination outweigh the
undesirable anticipated effects?
Intervention: Recommending PCV for all PCV -naïve adults aged 50 –64 years
Comparator: Risk-based recommendation for adults with CMC/IC
CMC: chronic medical conditions, IC=immunocompromising conditions 30□ Favors intervention
□ Favors current (risk -based for CMC/IC only)
□ Favors both
□ Favors neither
□ Varies
□ Don’t know Additional Work Group comment:
•Some members believed that
the interpretation would vary
by the PCV product
Values and Preferences
31
1. Does the target population feel that the desirable
effects are large relative to undesirable effects?
32□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know
Work Group comments
•Members with experience serving underserved populations, with many
underinsured or self -pay individuals, noted that these groups can be comfortable
with pneumococcal vaccines if benefits are clearly explained.
•The effectiveness of communication about benefits depends significantly on who
delivers the message and how much time is spent explaining it.
•There was discomfort in asserting what the target population thinks without more
evidence.
•Average populations may prioritize concerns about undesirable effects over
perceived benefits.
•Increased vaccine hesitancy observed in recent times makes the interpretation
challenging.
33
2. Is there important uncertainty about or variability
in how much people value the main outcomes*?
*Vaccine -type (VT) IPD, VT -non -bacteremic pneumococcal pneumonia, VT -pneumococcal deaths, serious adverse events 34□ Important uncertainty or variability
□ Probably important uncertainty or variability
□ Probably not important uncertainty or variability
□ No important uncertainty or variability
□ No known undesirable outcomes
Acceptability
Is the intervention acceptable to key stakeholders?
35
Is it acceptable to recommend PCV for all PCV -naïve
adults aged 50 –64 years?
•At the June ACIP meeting, presented
findings from Merck -funded healthcare
provider surveys1,2:
-challenges with implementing risk -based
vaccine recommendations (e.g., time
constraints, difficulties in identifying
vaccination history or underlying health
condition of the patient)
-support for lowering the age threshold of
the current age -based recommendation
1. Online survey conducted in February 2024 by ZS, funded by Merck. 502 HCPs (physicians, NP/PAs, pharmacists who vaccinate) par ticipated; majority (70%) physicians
2. Online survey conducted from March –May 2024 by OPEN Health, funded by Merck. Included a total of 340 HCPs consisting of physicia ns, nurse practitioners, physician assistants,
and pharmacists36□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know
Resource Use
Is the intervention a reasonable and efficient allocation of resources?
37
Summary of model findings, “adding” strategies
38•From the “adding” comparisons, all strategies improved health, but none were cost -saving
•Cost per QALY gained estimates for PCV20 had a wider range, more uncertainty than PCV21
•In two of three models, PCV21 had lower costs per QALY gained than PCV20
Leidner October 2024 ACIP meeting presentation 0 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000 1,000,000
Incermental cost -effectiveness ratio (ICER) ($/QALY)Cost -effectiveness estimates for PCV21 and PCV20 vaccination at age 50
and 65 years vs. current recommendations
PCV21
PCV21PCV20
PCV20
PCV20Tulane -CDC
Merck
model
Pfizer
model
Is PCV use for PCV -naïve adults aged 50 –64 years a reasonable
and efficient allocation of resources?
39□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know •Probably yes/yes:
-Despite the higher economic costs,
members valued the opportunity to
prevent more disease, particularly among
racial and ethnic groups who currently have
higher disease burden
Work Group comments
Probably No/Varies:
•Some Work Group members expressed concerns about the less favorable
economic analysis for PCV20 compared to PCV21 .
•Improved vaccination coverage among those with risk -based pneumococcal
vaccine indications could diminish the need for broader age -based
vaccination, while acknowledging that there has been insufficient success
•The decision varies when considering projections over the next 15 years,
e.g., indirect effects of pediatric vaccination, availability of new higher -
valency vaccines, data on duration of protection from vaccination, and
considerations of whether or not to give booster doses.
40
Feasibility
Is the intervention feasible to implement?
41
Is it feasible to implement PCV for all PCV -naïve adults
aged 50 –64 years?
42□ No
□ Probably no
□ Probably yes
□ Yes
□ Varies
□ Don’t know
Vaccine coverage tends to be lower in younger adults
even with an age -based recommendation
1.Week ending May 11, 2024. Vaccine coverage with the updated 2023 -2024 COVID -19 vaccine, defined as receipt of at least one vacci nation since September 2023.
2.Week ending May 11, 2024. Vaccine coverage for the 2023 -2024 influenza season
3.Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC , % represents those who received at least 2 doses
4.BRFSS 2022 data, % represents receipt of any pneumococcal vaccine dose 4350–64 yrs ≥65 yrs
COVID -19125.2% 40.6%
Influenza251.5% 73.8%
Recombinant
Zoster Vaccine312.2% (50 –59) 20.1% (60 –64) 22.8%
Pneumococcal437.3%* 69.7%
*Receipt of any pneumococcal vaccine dose among those with risk -based indications
Compared with vaccine coverage in adults aged ≥65 years,
pneumococcal vaccine coverage in adults aged 50 –64 years
with risk -based indication was disproportionately lower
1.Week ending May 11, 2024. Vaccine coverage with the updated 2023 -2024 COVID -19 vaccine, defined as receipt of at least one vacci nation since September 2023.
2.Week ending May 11, 2024. Vaccine coverage for the 2023 -2024 influenza season
3.Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC , % represents those who received at least 2 doses
4.BRFSS 2022 data, % represents receipt of any pneumococcal vaccine dose 4450–64 yrs ≥65 yrs (50–64 yrs)/
(≥65 yrs)
COVID -19125.2% 40.6% 0.62
Influenza251.5% 73.8% 0.70
Recombinant
Zoster Vaccine312.2% (50 –59) 20.1% (60 –64) 22.8%
Pneumococcal437.3%* 69.7% 0.54
*Receipt of any pneumococcal vaccine dose among those with risk -based indications
Work Group comments
•Age-based recommendations are generally easier to implement than risk -
based recommendations
•Lower vaccine coverage in younger adults is likely due to multiple factors,
such as healthcare access, perceived risk of disease or benefits from
vaccination.
-There is a larger proportion of adults aged 50 –64 years without health insurance
compared with adults aged ≥65 years1.
•Having a different age -based recommendation by vaccine product (e.g.,
PCV20, PCV21) will be more challenging to implement.
•Variability in health insurance coverage might keep PCV20 as the only
practical option for some individuals in the short term since PCV21 is new.
1. Health Insurance Coverage in the United States: 2022 (census.gov) 45
46EtR Domains Work Group Interpretation
Public Health Problem Yes
Equity Probably increased
Benefits and Harms
a. Benefits Moderate
b. Harms Minimal
c. Benefit>Harm? Favors intervention
Values and Preferences
a. Desirable>Undesirable? Probably yes/yes
b. Uncertainty? Probably not important uncertainty or variability
Acceptability Yes
Resource Use Probably yes/Yes
Feasibility Probably yes/YesSummary of Work Group Interpretations of EtR Domains
Key considerations: factors supporting lowering the
PCV age -based recommendation to age ≥50 years
1.The relatively high burden of pneumococcal disease in adults aged 50 –64 years,
particularly among those with risk conditions
2.Potential for improved vaccine uptake through an age -based recommendation,
which is easier to implement compared with the current risk -based
recommendation
3.Potential to reduce pneumococcal disease incidence in demographic groups
experiencing the highest burden
4.Projected health benefits from economic models* despite increased net costs
*Note that these are models that assumed that another vaccine dose is given later in life to ensure older adults are protecte d from disease 47
Key considerations: potential implications
1.Economic concerns: While our models showed health benefits, there were
significant concerns about the cost of lowering the age recommendation for both
PCV20 and PCV21 when considering overall health benefits to society
2.Market availability and insurance coverage: Concerns were raised that variability
in health insurance coverage might keep PCV20 as the only practical option for
some individuals in the short term, given that PCV21 is a newer vaccine
3.Ease of implementation: The Work Group agreed that having different age -based
recommendations by vaccine would be challenging to implement
48
Key considerations: uncertainties
1.How long is the duration of protection from a dose of PCV in adults?
2.What is the magnitude of indirect effects from pediatric PCV15/20 vaccination?
3.What might be the impact of higher -valency vaccines under development?
49
Summary: Work Group Interpretation
•Should a single dose of pneumococcal conjugate vaccine be
recommended for all PCV -naïve adults aged 50 –64 years?
50Balance 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
Should a single dose of pneumococcal conjugate vaccine be
recommended for all PCV -naïve adults aged 50 –64 years?
Is there sufficient information to move forward with a recommendation
Yes
•Policy options for ACIP consideration
-The majority recommended, but about a quarter said “do not recommend the
intervention”
•The higher cost/QALY gained for PCV20 compared to PCV21 in economic
analyses
•Uncertainties around key assumptions like the impact of pediatric PCV use
and duration of protection
•Concerns about the implications of a broad recommendation given the
differences in serotype coverage between PCV20 and PCV21
51
Should a single dose of pneumococcal conjugate vaccine be
recommended for all PCV -naïve adults aged 50 –64 years?
•Is there sufficient information to move forward with a recommendation
-Yes
•Policy options for ACIP consideration
-Recommend the intervention
52
Proposed policy option
•ACIP recommends a pneumococcal conjugate vaccine (PCV) for all PCV -
naïve adults aged ≥50 years
53
Clinical considerations
Proposed language
54
PCV-naïve adults* (or adults with unknown history)
•A single dose of PCV (PCV15, PCV20, or PCV21) is recommended for all
adults aged ≥50 years and for adults aged 19 –49 years with certain
underlying conditions or risk factors†who have not received a PCV or
whose vaccination history is unknown.
•If PCV15 is administered, a single dose of PPSV23§ should be
administered ≥1 year after the PCV15 dose. A minimum interval of 8
weeks can be considered if PCV15 is used in adults with an
immunocompromising condition¶, cochlear implant, or CSF leak.
*Includes adults who received PCV7 only
†Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; cerebrospinal fluid leak; diabetes mellitus;
generalized malignancy; HIV; Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple myeloma; nephrotic syndrome; solid organ
transplant; sickle cell disease; or other hemoglobinopathies.
§For adults who have received PCV15 but have not completed their recommended pneumococcal vaccine series with PPSV23, 1 dose o f PCV21 or PCV20 may be used if PPSV23 is not
available.
¶Chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV infect ion, Hodgkin disease, leukemia, lymphoma, multiple
myeloma, solid organ transplant, congenital or acquired asplenia, or sickle cell disease or other hemoglobinopathies .55DRAFT
Underlying
conditionsPrevious
vaccination
historyAge 19 –49 years Age ≥50 years
None None No vaccine recommendation
Chronic
medical
conditionsNone
CSF leak,
cochlear
implantNone
Immuno -
compromisedNonePCV15 PPSV23*OR
≥1yr
Use of 21 -Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Pra ctices — United States, 2024 | MMWR 56*If adults previously received PPSV23 before receiving a dose of PCV15, it need not be followed by another dose of PPSV23
†A minimum interval of 8 weeks can be considered for adults with an immunocompromising condition, cochlear implant, or cerebro spinal fluid
leakPCV20ORPCV21
PCV15 PPSV23*ORPCV20ORPCV21
≥1yr≥8wks†PCV-naïve adults (or adults with unknown history) DRAFT
PCV13 -experienced adults who completed the
recommended vaccine series
•Shared clinical decision -making is recommended regarding use of a
supplemental PCV20 or PCV21 dose for adults aged ≥65 years who have
completed their recommended vaccine series with both PCV13 and
PPSV23.
Rationale:
•No change is proposed to the age threshold. Under the previous
recommendation, PCV13 -vaccinated adults were only considered to have
“completed” their recommended vaccine doses after receiving one and
final dose of PPSV23 at or after age 65 years . Therefore, this scenario only
applies to adults aged ≥65 years who received both PCV13 and PPSV23 at
or after age 65 years. 57DRAFT (no change from current)
Underlying conditions Age ≥65 years
None
Chronic medical
conditions
CSF leak, cochlear
implant
Immuno -compromisedPCV13 -experienced adults who completed the
recommended vaccine series
Use of 21 -Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Pra ctices — United States, 2024 | MMWR58PCV13 PPSV23
≥1yr≥8wks*
PCV20ORPCV21
Shared clinical
decision -makingDRAFT (no change from current)
≥5yrs
*A minimum interval of 8 weeks can be considered for adults with an immunocompromising condition, cochlear implant, or cerebr ospinal fluid leak
PCV13 -experienced adults who have not completed
the recommended vaccine series
•A single dose of either PCV20 or PCV21 is recommended for adults aged
≥19 years who have started their pneumococcal vaccine series with PCV13
but have not received all recommended pneumococcal vaccine doses.
Change:
•Removed the option to complete vaccine series with PPSV23 for PCV13 -
experienced adults
Rationale:
•The potential need for repeated PPSV23 doses in adults who received
PCV13 was one of the reasons for the complexity of the recommendation.
59DRAFT
Underlying
conditionsAge 19 –64 years Age ≥65 years
None
Chronic
medical
conditions
CSF leak,
cochlear
implant
Immuno -
compromised≥8wksPCV13 -experienced adults who have not completed the
recommended vaccine series (current recommendation)
60≥5yrs≥5yrs≥1yr
OR
PCV13PCV13
PCV13PCV13
PPSV23
PPSV23 PPSV23PPSV23≥1yr PCV20PCV21
OR
OR
PCV20PCV21
OR
PPSV23PCV20PCV21
OR
OR≥8wksOR
Underlying
conditionsAge 19 –64 years Age ≥65 years
None
Chronic
medical
conditions
CSF leak,
cochlear
implant
Immuno -
compromised≥8wksPCV13 -experienced adults who have not completed
the recommended vaccine series (proposed)
61≥5yrs≥5yrs≥1yr
OR
PCV13PCV13
PCV13PCV13
PPSV23
PPSV23 PPSV23PPSV23≥1yr PCV20PCV21
OR
OR
PCV20PCV21
OR
PPSV23PCV20PCV21
OR
OR≥8wksOR
Acknowledgements
•ACIP and the Pneumococcal Vaccines Work Group
•Active Bacterial Core surveillance sites and program
•Charles Stoecker, Yin Wang (Tulane University)
•Wesley Self, Jackson Resser (Vanderbilt University Medical Center)
•CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Andrew Leidner,
Sofia Bletnitsky, Kristin Andrejko, Emma Accorsi, Wei Xing, Adam Cohen, Alison
Albert, Shelby Miller, Noele Nelson, Kimberly Fox, Pedro Moro, Bo -Hyun Cho,
Elizabeth Velazquez, Janelle King, Fangjun Zhou, Peng -Jun Lu, Anup Srivastav, Carla
Black, Marc Fischer, Laurie Orell, Cheryl Ward, Rebecca Morgan, Doug Campos -
Outcalt
62
Supplementary Slides
63
Search strategy
64Database Strategy Run Date Records
PubMed (PCV15 OR PCV20 OR "15 -valent pneumococcal
conjugate vaccine" OR "20 -valent pneumococcal
conjugate vaccine") AND adult; Filters applied: English,
Humans, from 2021/2/19 - Present. August 3, 2024 94
PubMed (PCV21 OR V116 OR "pneumococcal conjugate vaccine
21" OR "pneumococcal conjugate vaccine 21 -valent")
AND ("2023/09/19"[Date - Publication] : "3000"[Date -
Publication])September 8,
202466
Clinicaltrials.gov V114, Filter: "Adult (18 -64)", "Phase 3" August 17, 2024 8
Clinicaltrials.gov 20vPnc, PCV20, 20 -valent PCV, 20 -valent pneumococcal
conjugate vaccine; Filter: "Adult (18 -64)", "Phase 3" August 17, 2024 18
Clinicaltrials.gov 1. Intervention: “V116”, filter: “Adult (18 –64)”, “Phase
3”
2. “PCV21”, filter: “Adult (18 –64)”, “Phase 3”
3. “21 valent pneumococcal conjugate vaccine”, filter:
“Adult (18 –64)”, “Phase 3”September 8,
20241. 7
2. 0
3. 7 (all duplicate
with 1)
Study Study designCountry (or
more detail, if
needed)Age (rangeTotal
populationN Intervention N comparison OutcomesFunding
source
Song 2021Phase III randomized
controlled trial US, Korea,
Spain, TaiwanAdults ≥50 years of
age, PCV followed by
PPSV23 12 months
later627 325 302Immunogenicity,
SafetyMerck
Mohapi 2022Phase III randomized
controlled trial USAdults ≥18 years of
age with HIV, PCV
followed by PPSV23 8
weeks later298 150 148Immunogenicity,
SafetyMerck
Platt 2022Phase III randomized
controlled trialUS, Japan,
Spain, Canada,
TaiwanAdults ≥50 years of
age1202 602 600Immunogenicity,
SafetyMerck
Simon 2022Phase III randomized
controlled trialUS, Australia,
Chile, Denmark,
Finland, UKAdults ≥50 years of
age2340 2107 233 Immunogenicity, Safety Merck
Severance 2022Phase III randomized
controlled trialUSAdults ≥50 years of
age1200600 (concomitant
with QIV)600 (sequential QIV
administration)Immunogenicity, Safety Merck
V110 -911Phase III randomized
controlled trialUS, Puerto RicoAdults ≥50 years of
age850 (includes 426
who received
PPSV23 214 (concomitant
with mRNA -1273)210 (sequential mRNA -
1273 administration)Immunogenicity and
safetyMerckPCV15 studies included in the review of evidence
65
Study Study designCountry (or
more detail, if
needed)Age (rangeTotal
populationN Intervention N comparison OutcomesFunding
source
Essink , 2022Phase III
randomized
controlled
trial US and
SwedenAdults ≥ 18 -49
years (34.0, SD
8.8)448 336 (PCV20) 112 (PCV13)
Immunogenicity,
SafetyPfizerAdults ≥ 50 -59
years (54.9, SD
2.8)445 334 (PCV20) 111 (PCV13)
Adults ≥ 60
years (64.6, SD
4.8)2997 1507 (PCV20)1490
(PCV13+PPSV23)
Hurley, 2021 Phase II
randomized
controlled
trial USAdults 60 - 64
years (62.0, SD
1.4)444 222 222Immunogenicity,
SafetyPfizer
Haranaka , 2024Phase III
randomized
controlled
trialJapan,
South
Korea, and
TaiwanAdults aged
≥60 years (66.1,
SD 4.7)1421 711 (PCV20)710
(PCV13+PPSV23)Immunogenicity,
SafetyPfizerPCV20 studies included in the review of evidence
66
PCV21 studies included in the review of evidence
*participants who received at least one dose of study intervention67Study Study design Country Age Total population N Intervention* N comparison OutcomesFunding
source
Platt, 2023 RCT (Phase II) US Adults ≥50 years 508 254 PPSV23: 254 Immunogenicity and SafetyMerck
Platt, 2024RCT (Phase III);
pivotal studyUS, Australia, Belgium,
Chile, Germany, Korea,
New Zealand, Puerto
Rico, Sweden, Taiwan,
TurkeyHealthy adults ≥50 years,
pneumococcal vaccine – naïve
2,6631,179 PCV20: 1,177
Immunogenicity and Safety Merck
Healthy adults 18 - 49 years,
pneumococcal vaccine – naïve200 PCV20: 100
V116 -005RCT (Phase III)US Adults ≥50 years 1,080(V116 + QIV,
coadministered): 536(QIV followed by V116):
536Immunogenicity and
SafetyMerck
Scott, 2024RCT (Phase III)US, Canada, Israel,
France, Italy, Japan,
Korea, Spain, TaiwanAdults ≥50 years, previous PPSV23
≥1 year prior to enrollment350 229 PCV15, n=117
Immunogenicity
and
SafetyMerckAdults ≥50 years, previous PCV13 ≥1
year prior to enrollment261 174PPSV23
N=85
Adults ≥50 years, PCV13+PPSV23,
PCV15+PPSV23, PCV15, PCV20, or
PPSV23+PCV13 ≥1 year prior to
enrollment106 105 None
V116 -007 RCT (Phase III)Belgium, Chile, France,
South Africa,
Thailand,
United StatesAdults ≥18 years living with HIV; 36%
prior PCV13 or PPSV23*313 155 PCV15+PPSV23, n=156 Immunogenicity and Safety Merck
V116 -008 RCT (Phase III)United States, Australia,
Canada, Chile, Japan,
South Korea, New
Zealand, Poland, Adults aged 18 –64 years with
increased risk for pneumococcal
disease†518 386 PCV15+PPSV23, n=130 Immunogenicity and Safety Merck
V116 -010 RCT (Phase III)Argentina, Australia,
Colombia, Germany,
Israel, South Korea, New
Zealand, Spain, Taiwan,
Turkey, United KingdomAdults aged ≥50 years,
pneumococcal vaccine -naïve 1,484 739 PPSV23: 741 Immunogenicity and Safety Merck