Document text
Nationa l Center for Immunizatio n & Respirator y Diseases
Evidence to Recommendations Framework (Preliminary):
Use of 20-valent Pneumococcal Conjugate Vaccine in U.S. Children
Miwako Kobayashi, MD, MPH
Pneumococcal Vaccines Work Group
Advisory Committee on Immunization Practices
February 22, 2023
Evidence to Recommendations (EtR) framework
EtR Domain 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?2
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?Evidence to Recommendations (EtR) framework
EtR Domain 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?
Equity • What would be the impact of the intervention on health equity?3
All children under age 2 years have the same
pneumococcal vaccine recommendations
• 3 primary series and a booster=“3+1” schedule
PCV PCV PCV PCV 2months 4months 12–15 months 6months
Primary Series Booster
Either PCV13 or PCV15 can be used for U.S. children.
4
Primary Series Booster
Currently, either PCV13 or PCV15 can be used for U.S. children.All children under age 2 years have the same
pneumococcal vaccine recommendations
• 3 primary series and a booster=“3+1” schedule
PCV PCV PCV PCV 2months 4months 12–15 months 6months
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?
5
Children age ≥2 years with certain underlying conditions
recommended to receive PPSV23 in addition
PPSV23 Recommended
PCV doses Recommended
PCV doses Healthy
children
MC, CSF leak,
cochlear
implant
≥8 weeks
Recommended
PCV doses PPSV23 PPSV23 Immuno-
ompromised
≥8 weeks ≥5 years
MC aged 6–18
years PPSV23
C
c
C
Note: Excludes catch-up vaccination schedules.
CMC=chronic medical conditions, including chronic heart disease, chronic lung disease, diabetes mellitus
CSF=cerebrospinal fluid
Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization
Practices — United States, 2022 | MMWR (cdc.gov) 6
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?
7
PICO
Question Should PCV20 be recommended as an option for pneumococcal vaccination
for U.S. children?
Population U.S. children aged 2–18 years with All U.S. children aged <2 years underlying medical conditions
Intervention PCV20 according to currently
recommended dosing and PCV20 (without PPSV23) schedules
Comparison PCV13 or PCV15 according to currently recommended dosing and schedules
Outcomes VT-IPD, VT- pneumonia, VT- AOM, VT- pneumococcal deaths, serious adverse events following vaccination
8 VT: vaccine-type, IPD: invasive pneumococcal disease, AOM: acute otitis media
EtR Dom ain: P ublic Healt h Problem
Summary of 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.
• Risk of disease remains high in children with underlying conditions that increase the risk of pneumococcal disease.
• In 2018–2019, the proportion of IPD caused by vaccine serotypes was:
• PCV20, non-PCV13: ~30% of IPD
• PCV15, non-PCV13: ~15% of IPD
Gierke. February 2023 ACIP meeting presentation
King. February 2023 ACIP meeting presentation 10
Public Health Problem
Is pneumococcal disease of public health importance in U.S.
children?
□
□□□□□ N o
Probably no
Probably yes
Yes Varies Don’t know
11
Public Health Problem
Is pneumococcal disease of public health importance in U.S.
children?
□
□ □ □ □ □ N o
Probably no
Probably yes
Yes Varies Don’t know • Variability in Work Group members’
interpretations for children aged <2 years due to significant reductions in pneumococcal disease.
• Most agreed that pneumococcal disease continues to be of public health importance due to the remaining disease burden.
12
EtR Dom ain: Benefits and Harms
Outcomes (Benefits)
Outcome Importance Description
VT- IPD Critical Studies assessing PCV20 against these
VT- non-bacteremic
pneumococcal pneumonia clinical outcomes are currently not Critical
available
VT- acute otitis media PCV20 immunogenicity studies for Critical GRADE
VT- pneumococcal deaths Critical PCV13/PPSV23 clinical outcome studies for background
AOM=acute otitis media, IPD=invasive pneumococcal disease, VT=vaccine-type 14
Outcomes (Harms)
Outcome Importance Description
Serious adverse events Critical Safety data for PCV20 are available
15
Background
PCV13 effectiveness (3+1) in children, VT-IPD
Study Population Dosin g schedule
(Ye ar o f
introduction) Me thod Outcome Vaccine (95% CI)
Effectiveness
Savulescu,
2022 Children 2m – 59m; Spidnet
(12 European 2+1 or 3+1
(variable) Indirect cohort 3 + 1 doses, ≥12 months 89.7% (adjusted*) (82, 94)
sites, 2012 -
2018
V an
de r
Linden,
2016* Childre n <2
years; German y
(GNRCS) 3+1 (Decembe r
2009) Indirec t
cohort PCV13-type; post-booster 91% (61, 99)
Weinberger,
2016 Childre n 2.5 –
56m; German y
(ESPED) 3+1 (Decembe r
2009) Indirec t
cohort PCV13-type +6C; ≥2 dose before 12
months or one dose on/afte r 12
months 85% (adjusted) (64, 94)
Dominguez,
2017 Childre n 7m -
59m; Sp ain
(Catalonia) 3+1 (public, Ju ly
2016) Matche d
case-
control PCV13-type; 7-59m; ≥2 doses before
12 months o r one dose afte r 12
months 78.9% (52.8, 90.5)
Moore ,
2016 Childre n 2-
59m; US 3+1 (2010) Matche d
case-
control PCV13-type; ≥1 dose 86.0%
(unadjusted) (75.5, 92.3)
* Adjusted by site, age, year of notification and at least one underlying disease
Post-licensure vaccine effectiveness studies have shown that PCV13 is highly effective against
VT-IPD 17
PCV13 effectiveness, VT-pneumococcal pneumonia
Study Population Dosing schedule
(Year of introduction) Method Outcome VE (95% CI)
Zhang, 2021 Children born
D
ecember 2016
– Novembe r
2018, China 3+1 (2017) Indirect cohort;
VT-CAP defined as hospita l
discharge diagnosis code of
pneumonia + deep uppe r
respiratory aspirate with
PCV13 serotypes. VT-CAP; ≥3
doses 62.1 %
(adjusted) (26.3 , 80.5)
Lew
nard,
2021* Children 4 to 59
months, Israel 2+1 (2010) Nested c ase-control ;
Used: • PCV-conferred protection
against VT pneumococca l
carriage
• Protection agains t
progression fr om carriage t o
pneumonia CAP attributed
t o PCV13 , 12-
59 months; 2+1
doses 77
.0 %
(adjusted) (-16.0, 100.0)
CAP=community acquired pneumonia
*funded by Pfizer Limited data on PCV13 effectiveness against VT-pneumococcal
pneumonia in children. PCV13 likely protective. 18
PCV13 effectiveness, VT-AOM
Study Population Dosing schedule
(Year of introduction) Method Outcome VE (95% CI)
Pichichero,
2018* Children ≤ 36
month s, United
States 3+1 (2010) Prospective
longitudina l
cohor t (PCV1 3 v
PCV 7 period) PCV13-non-PCV7 serotype s;
PCV1 3 full primar y serie s
(regardle ss of booste r statu s)
vs. PCV7 f or middle-ear flui d
samples a t onse t of AOM
Serotype 3; PCV13 ful l
primary serie s (regardle ss of
booste r status) vs. PCV 7 f or
middle-ear fluid samples a t
onse t of AOM 86 %
(adjusted)
5 %
(adjusted) (61 , 94)
(–181 , 68)
Oc
hoa-
Gondar, 2015 ≤14 years; Spain
(Catalonia region) 3+1 (2016, publicly available) Indirect cohort PCV13-type; ≥1 dose 62% (unadjusted) (-141, 95)
Dagan, 2021* Children 5 to 35 months, Israel 2+1 (2010) Nested case-control PCV13-type; ≥2 doses vs. 0 doses 77.4% (adjusted) (35.3, 92.1)
Serotype 3; ≥2 doses vs. 0 doses 89.0% (adjusted) (23.9, 98.4)
Limited data on PCV13 effectiveness against VT-pneumococcal AOM in
children. PCV13 likely protective. *funded by Pfizer 19
PPSV23 effectiveness, VT-IPD (Pre-PCV U.S. data)
Pre-PCV era data showed that PPSV23 is protective against VT-IPD among
children with underlying medical conditions.
Fiore et al. EID 1999 20
PPSV23 effectiveness, non-invasive pneumococcal
disease
• No study on PPSV23 VE against AOM identified in a recent systematic review1
• Two randomized-controlled trials (RCTs)2,3 evaluated PCV7-PPSV23 in series
against AOM
• No efficacy in the PCV7-PPSV23 groups
1. Marra et al. Value Health 2022
2. Veenhoven et al. Lancet 2003
3. Van Kempen et al. Int J Pediatr Otorhinolaryngol 2006 21
GRADE: PCV2 0 us e in children
Evidence retrieval: PCV20 use in children
Clinicaltrials.gov
N=12
4 studie s include d fo r GRADE
Phase I I tria l (published), N=1
Phase II I trial s (unpublished), N=3 Pubmed
N=62
PCV20 routi ne use
(N=3)
Immunogenicity (N=2)
Safety (N=3) PCV20 use i n childre n
wit h underlyi ng
conditions
(N=1)
Immunogenicity (N=1)
Safety (N=1) Unpublishe d data from
pharmaceutica l
company
N=3
23 Search terms used are provided in supplementary slides
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 immune responses* vs. PCV13 for most of the
13 shared serotypes
•Post dose 3 :
•PCV20 did not meet noninferiority criteria vs. PCV13 for some serotypes
•Post dose 4 :
•PCV20 noninferior to PCV13 for all 13 shared serotypes
•PCV20 noninferior to PCV13** for all 7 additional serotypes
*measured as IgG GMCs and GMRs
**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 B7471011 24
Summary of evidence:
Harms, children <2 years
• Serious adverse events (SAEs) across 3 studies (dose 1 through 6 months after
dose 4):
• PCV20: 4.5% (n=1,567) vs PCV13: 3.7% (n=1,376)
• None were considered to be vaccine-related
1. Senders et al. PIDJ 2021
2. Pfizer B7471011, unpublished data
3. Pfizer B7471013, unpublished data, limited to US and Puerto Rico sites 25
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 Importance Included in
evidence profile Certainty for
healthy individuals
VT- IPD Critical Yes Moderate
Benefits VT-pneumonia Critical Yes Moderate
VT- AOM Critical Yes Moderate
VT- pneumococcal
deaths Critical Yes Moderate
Harms SAEs following
vaccination Critical Yes Moderate
AOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine-type 26
Benefits and Harms
How substantial are the desirable anticipated effects?
Routine PCV20 use for children aged <2 years
□ Minimal
Small
Moderate Large Varies Don’t know □□□□□• PCV20 provides the broadest
serotype coverage among available PCVs.
• Unknown how substantial the protection conferred from PCV20 will be based on available data.
27
Benefits and Harms
How substantial are the undesirable anticipated effects?
Routine PCV20 use for children aged <2 years
□ Minimal
Small
Moderate Large Varies Don’t know □ □ □ □ □
28
Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
Routine PCV20 use for children aged <2 years
□ Favor s intervention*
Favor s current recommendation
Favor s both
Favor s neither
Varies
Don’t know □
□□□□
*Intervention: PCV20 use
Comparison: PCV13 or PCV15 use 29
Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
• Routine PCV20 use for children aged <2 years
Favors Intervention (PCV20):
• PCV20 is expected to prevent more disease compared with current PCVs (PCV13, PCV15)
Favors Both (PCV20 or PCV13/PCV15): • Clinical implications of the lower immunogenicity PCV20 compared with PCV13
unknown
• Clinical implications of improved immunogenicity of PCV15 against serotype 3*
unknown
*Banniettis. February 24, 2022 ACIP meeting presentation 30
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 B7471014 31
Summary of evidence:
Harms, children 2–18 years with underlying conditions
• Serious adverse events (SAEs) :
• PCV20: 0.6% (n=831)
• None were considered to be vaccine-related
Pfizer unpublished data from B7471014 32
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 Importance Included in evidence
profile Certainty for children
with underlying
conditions
VT-IPD Critical Yes Very Low
Benefits VT-pneumonia Critical Yes Very Low
VT-AOM Critical Yes Very Low
VT-pneumococcal
deaths Critical Yes Very Low
Harms SAEs following
vaccination Critical Yes Very Low
AOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine-type 33
Benefits and Harms
How substantial are the desirable anticipated effects?
PCV20 use for children aged 2–18 years with underlying medical conditions
□ Minimal
Small
Moderate Large Varies Don’t know □□□□□• PCV20 provides the broadest
serotype coverage among available PCVs.
• Unknown how substantial the protection conferred from PCV20 will be based on available data.
• No data from this population.
34
Benefits and Harms
How substantial are the undesirable anticipated effects?
PCV20 use for children aged 2–18 years with underlying medical conditions
□ Minimal
Small
Moderate Large Varies Don’t know □□□□□
35
Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
PCV20 use for children aged 2–18 years with underlying medical conditions
□
□
□ □ □ □ Favor s intervention*
Favor s current recommendation
Favor s both
Favor s neither
Varies Don’t know *Intervention: PCV20 use
Comparison: PPSV23 use after currently
recommended PCV (PCV13 or PCV15) doses
36
Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
PCV20 use for children aged 2–18 years with underlying medical conditions
Favors Intervention (PCV20):
• PCV20 is expected to prevent more disease compared with current recommendations (PPSV23 after recommended PCV13/15 doses)
Favors Both (PCV20 or PPSV23 after recommended PCV13/PCV15 doses): • No data on PCV20 use in this population
• Clinical implications of improved immunogenicity of PCV15 against serotype 3*
unknown
*Banniettis. February 24, 2022 ACIP meeting presentation 37
EtR Dom ain: Equity
Compared with coverage among children with private
insurance only , children who were uninsured, and those
insured by Medicaid and other insurance was lower
≥3 PCV doses (%) ≥4 PCV doses (%)
Private insurance only (Ref)
(N=16,629) 96.2 90.0
Any Medicaid (N=10,200) 91.3* 78.8*
Other insurance (N=2,168) 91.1* 80.6*
Uninsured (N=608) 83.9* 62.3*
PCV=pneumococcal conjugate vaccine
*statistically significant difference compared with Ref.
Hill et al. MMWR 2023 39
Nationally representative PPSV23 vaccine coverage
data among children with indications are limited
• Vaccine coverage among children with sickle cell anemia, Michigan Medicaid program1
• 4PCV + 1 PPSV23 at age 5 years: 64%
• 4PCV + 2 PPSV23 at age 10 years: 53%
• Self-administered survey of parents/guardians of children aged <18 years with
nephrotic syndrome2
• PPSV23 receipt: 43%
• Data from single-center quality improvement studies among children seen in specialty
care clinics reported 20–30% PPSV23 coverage at baseline3,4
1. Reeves et al. Pediatric Blood & Cancer, 2018
2. Tran et al. Frontiers in Pediatrics, 2021
3. Mirza et al. The Ochsner Journal, 2022 40 4. Harris et al. Pediatrics, 2022
41IPD incidence
rate difference
in children aged ≤17 years by census tract poverty,
ABCs 2010–2019
CDC ABCs, unpublished data All Serotypes PCV13 Serotypes PCV15/non-PCV13
PCV20/non-PCV13 PCV20/non-PCV15 Nonvaccine Serotypes
42IPD incidence
rate difference
in children aged ≤17
Nonvaccine Serotypes
years by census tract poverty,
ABCs 2010–2019
CDC ABCs, unpublished data PCV15/non-PCV13
PCV20/non-PCV13 PCV20/non-PCV15 For all serotypes and PCV13 serotypes, IPD incidence rate
difference between the highest and lowest census tract poverty categories decreased after PCV13 introduction. All Serotypes PCV13 Serotypes
43IPD incidence
rate difference
in children aged ≤17 years by census tract poverty,
ABCs 2010–2019
CDC ABCs, unpublished data All Serotypes PCV13 Serotypes PCV15/non-PCV13
PCV20/non-PCV13 PCV20/non-PCV15 Nonvaccine Serotypes Essentially no IPD incidence rate difference for the
PCV15, non-PCV13 serotypes.
44All Serotypes PCV13 Serotypes PCV15/non-PCV13
IPD incidence
rate difference
in children aged ≤17 years by census tract poverty,
ABCs 2010–2019
CDC ABCs, unpublished data PCV20/non-PCV13 PCV20/non-PCV15 Nonvaccine Serotypes • IPD incidence rate difference for the additional serotypes
contained in PCV20 remain
• Slightly larger incidence rate difference for non-vaccine serotypes
Equity
What would be the impact of recommending PCV20 for U.S.
children on health equity?
□ Reduced
Probably reduced
Probably n o impact
Probably increased
Increased
Varie s
Don’t kno w □
□
□
□
□
□
45
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 Children
Equity
What would be the impact of recommending PCV20 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 could simplify the pneumococcal vaccine recommendations and
improve vaccine coverage.
Summary of Work Group Interpretation of the EtR Domains (Preliminary)
EtR Domains 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)
Equity Probably increased (different opinions)
48
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, Noele Nelson, Pedro Moro, Elizabeth Velazquez, Marc Fischer, Katie Hamilton, Noelle Sobotka, Rebecca Morgan, Doug Campos-Outcalt
49
Supplementar y Slides
GRADE Summary of Evidence
Search strategy: PCV20 use in children
No.
Database Strategy identified
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:
o 3+1 series for infants starting the vaccine series as currently recommended
o Catch-up vaccine schedule for older infants and children who did not start the 3+1 series
in time
o Use of PCV20 to complete the PCV13 series
o Use of PCV20 in series with PPSV23 in older children with underlying conditions in series
with PPSV23 Included in
GRADE
12 3*
Pubmed
Medline “PCV20” or “20-valent pneumococcal conjugate vaccine” Included studies using the criteria listed above 62 1
Additional resources Unpublished and other relevant data by consulting with the vaccine manufacturer
2 3*
*Same trials. Unpublished data from these trials were obtained from pharmaceutical companies. 51
Included Studies: Routine PCV20 Use in Children Aged <2 years
Author, year Study
design Intervention Country Age Total population N Intervention N comparison Outcomes Funding source
Phase II RCT 42–98
Senders, 2021 in healthy full-term
infants PCV20 @ 2, 4, 6,
and 12 months of age US days of age at
consent 460 232 228 Immuno-
genicity and safety Pfizer
B7471011 Phase III RCT
in healthy full-term
infants PCV20 @ 2, 4, 6,
and 12 – 15 months of age US, Puerto Rico 42–98
days of age at
consent 1998 1001 997 Immuno-
genicity and safety Pfizer
US, Puerto 42–98
B7471013 Phase III RCT in healthy infants PCV20 @ 2, 4, 6, and 12 – 15 months of age Rico,
Canada,
Chile, Argentin a, EU days of age at
consent 1511 1000 551 Safety Pfizer
52
RCT=Randomized Controlled Trial
Certainty assessment № of patients Results
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Intervention comparison Relative
(95% CI) Absolute
(95% CI)
-Vaccine effectiveness
21 2 RCT Not
serious Not serious Seriousa Not 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
noninferiority criteria for some serotypes after dose 3.
• PCV20 noninferior to PCV13 for all 13 shared serotypes after dose 4.
• PCV20 noninferior to PCV13
b
for all 7 additional serotypes after dose 4. Moderate Critical GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years
a. These are all immunogenicity studies and there are no correlates of protection for most outcomes.
b. Compared with serotype with lowest immune response among PCV13 serotypes except for 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 Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct
1;40(10):944-951. doi: 10.1097/INF.0000000000003277. 53 2.B7471011. A Phase 3, Randomized, double-blind trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in healthy infants
Certainty assessment № of patients Results
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Intervention Comparison Relative
(95% CI) Absolute
(95% CI)
Serious Adverse Events (SAEs) following vaccination
-21 3 RCT Not Not serious Not serious Seriousa Not serious 4.5% 3.7% No vaccine-related
serious (n=1567) (n=1376) serious adverse events Moderate Critical
reported GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years
a. No v
accine-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 conjugate 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 healthy infants. Data limited to U.S. and Puerto Rico sites.
54
Included Study: PCV20 Use in Children Aged 2–18 Years with Underlying
Medical Conditions
Author, year
B7471014
Study design Intervention Country Age Total
population N Intervention N comparison Outcomes
Funding
source
Single dose PCV20 @ 15m to <24m; 15m
previous
vaccination ≥3 to
<24m 209 209 N/A
Phase III doses of PCV13
Immuno-genicity and
safety Pfizer Clinical Trial
in healthy
children,
some previously Single dose PCV20 @ 2y to <5y; previous
vaccination ≥3
doses of PCV13 US 2y to <5y 216 216 N/A
vaccinated Single dose PCV20 @ 5y to <10y
Single dose PCV20
@ 10 to <18y 5y to <10y 201 201 N/A
55 10y to <18y 205 205 N/A
GRADE Summary of Findings: PCV20 Use in Children Aged 2–18 Years
with Underlying Medical Conditions
Certainty assessment № of patients Results
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Intervention comparison Relative
(95% CI) Absolute
(95% CI)
Vaccine effectiveness
11 Non-RCT Very
Serious
a Not
applicable Very
Seriousb,c Not
serious Not serious 752-75 7 None IgG 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 groups
Very Low Critical
a. Study design is an open label non-randomized controlled trial with no comparator group. Downgraded for lack of randomization, lack 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 Age 56
GRADE Summary of Findings: PCV20 use in Children Aged 2–18
Years With Underlying Medical Conditions
Certainty assessment № of patients Results
Certainty Importance № of
studies Study design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations PCV20 Intervention Relative
(95% CI) Absolute
(95% CI)
Serious Adverse Events (SAEs) following vaccination
11 Non-
randomized
trial Serious
a Not
applicable Seriousb Seriousc Not serious 0.6%
(n=831) No vaccine-related
SAEs reported Very Low Critical
a. Study design is an open label non-randomized controlled trial with no comparator group
b. Study population did not include children with underlying conditionsc. 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
57