Document text
GRADE/Evidence to Recommendations Framework (EtR)
for GSK Pentavalent (MenABCWY) Vaccine
Sarah F. Schillie, MD, MPH, MBA
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization & Respiratory Diseases
1
Meningococcal Vaccine Recommendations
Routine schedule
–One MenACWY* dose at age 11 –12 years and a booster at age 16 years
–Two MenB** doses at age 16 –23 years (shared clinical decision -making [SCDM])
•Preferred age range: 16 –18 years
Increased risk, MenACWY*
–Asplenia, complement deficiency, complement inhibitor use, and HIV infection
–Some microbiologists
–Exposure during an outbreak
–Travel to hyperendemic areas
–First -year college students (if not previously vaccinated at age ≥16 years)
Increased risk, MenB**
–Asplenia, complement deficiency, and complement inhibitor use
–Some microbiologists
–Exposure during an outbreak
*MenACWY vaccines are interchangeable; **MenB vaccines are not interchangeable2
Two new MenABCWY vaccines:
–Pfizer (Penbraya, ACIP vote October 2023)
–GSK (ACIP vote anticipated February 2025)
Each vaccine is a combination of an existing:
–MenACWY vaccine
–MenB vaccine
Each vaccine assessed separately by Work Group
–Lack of data directly comparing Pfizer and GSK Pentavalent vaccinesPentavalent MenABCWY Vaccines
and
3
Pfizer and GSK MenABCWY Vaccines
Pfizer (Penbraya) GSK*
ACWY component Nimenrix (not licensed in U.S.) Menveo
B component Trumenba Bexsero
Schedule 2 doses, 6 months apart 2 doses, 6 months apart*
Age 10–25 years 10–25 years*
*Vaccine not yet licensed in U.S. and this slide represents anticipated schedule and age indications 4
Policy Questions
PICO 1:
Should the GSK pentavalent vaccine be included as an option for MenACWY/MenB
vaccination in people currently recommended to receive both vaccines at the same visit?
– For example, 16 year- olds*
PICO 2:
Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only?
–For example, 11 –12 year -olds
PICO 3:
Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB only?
– For example, during a serogroup B outbreak
*16 year -olds who decide to receive the MenB vaccine based on shared clinical decision -making5
Combined Policy and PICO Questions
6Policy QuestionShould the pentavalent vaccine be included as an option for people currently
recommended to receive MenACWY and MenB, MenACWY only, or MenB only ?
PopulationAll individuals aged ≥10 years currently recommended to receive MenACWY+MenB,
MenACWY , or MenB vaccine
Intervention Vaccination with the pentavalent vaccine
Comparison Vaccination with currently licensed MenACWY+MenB, MenACWY , or MenB vaccine
Outcomes•Meningococcal disease caused by serogroups A, B, C, W, and Y
•Short- term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
Outcomes Table
Outcome Importance* Included in
Evidence Profile
Meningococcal disease caused by serogroups
A, B, C, W, and YCritical Yes
Persistent immunity Important Yes
Short -term immunity Critical Yes
Interference with other recommended vaccines administered concurrentlyImportant Yes
Serious adverse events Critical Yes
Non -serious adverse events Important Yes
*Three options: critical, important but not critical, of limited importance for decision making
7
How PICOs Translate into Schedule Options for
Healthy Adolescents
8OptionsDose at age
11—12 yearsDose at age
16 yearsDose at age
16 years
Standard of care (MenACWY only) Q Q -
Standard of care (MenACWY + MenB) Q Q+B B
PICO 1 (MenABCWY as option for MenACWY + MenB) Q P B
PICO 2 (MenABCWY as option for MenACWY) P P B
PICO 3 (MenABCWY as option for MenB) Q P P
Combination of all 3 PICOs P P P
Legend
Q = MenACWY (quadrivalent)
B = MenB
P = MenABCWY (pentavalent)
EtR Domain Question
Public health
problemIs invasive meningococcal disease a problem of public health
importance?
Benefits and
harmsHow substantial are the desirable anticipated effects?
How substantial are the undesirable anticipated effects?
Do the desirable anticipated effects outweigh the undesirable effects?
What is the overall certainty of the 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 outcome?
Acceptability Is the intervention acceptable to key stakeholders?
Resource use Is the intervention a reasonable and efficient allocation of resources?
Equity What would be the impact of the intervention on health equity?
Feasibility Is the intervention feasible to implement?
9
Public health problem
Is invasive meningococcal disease a problem of public health importance?
Meningococcal Disease
Most often presents as meningitis or bacteremia
Progresses rapidly
10–15% of cases are fatal (even with appropriate antibiotic
therapy)
~20% of survivors experience long -term sequelae
–Cognitive deficits
–Hearing loss
–Limb amputations
11
Public Health Problem
Is invasive meningococcal disease a problem of public health importance?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
12
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?
Studies Included in Review of Evidence
14Study ID(s) Location(s)Study
DesignPhase Blinding PopulationAuthor, year or
Study IDPeriod
NCT01210885
NCT01367158
NCT02451514Chile, Colombia,
PanamaRCT IIObserver -
blindHealthy, immuno -naïve individuals aged
11-18 yearsSaez -Llorens 2015a Dec 2010— Jul 2011
Saez -Llorens 2015b Jul 2011— Jul 2012
Open- label*Prior participants + individuals w/o
meningococcal vaccine historySaez -Llorens 2018 Jun 2015— Dec 2015
NCT01272180
NCT01992536Poland, USA RCT IIObserver -
blindHealthy, immuno -naïve individuals aged
10-25 yearsBlock 2015 Aug 2011— Sep 2012
Szenborn 2018 Dec 2013— Apr 2015
NCT02140762
NCT02285777USA RCT IIbObserver -
blindHealthy, immuno -naïve individuals aged
10-18 yearsWelsch 2018 May 2014— Jun 2015
NCT02212457
NCT02946386Finland, Poland RCT IIbObserver -
blindHealthy, immuno -naïve individuals aged
10-18 yearsVesikari 2021Aug 2014— Mar 2016
Nov 2016— Feb 2018
NCT03587207 Czechia RCT II Open- labelHealthy, immuno -naïve individuals aged
10-25 yearsBeran 2021 Jul 2018— Dec 2018
NCT04502693Australia, Canada,
Czechia, Estonia,
Finland, Turkey, USARCT IIIObserver -
blindHealthy individuals aged 10 -25 years w/o
history of meningococcal disease or
vaccinationv72_72 Aug 2020— Sep 2022
NCT04707391 Argentina, Australia,
Canada, USARCT IIIObserver -
blindHealthy individuals aged 15 -25 years
vaccinated with MenACWY ≥4 years prior
and w/o history of meningococcal diseaseMenABCWY_019 Jan 2021— Sep 2023
*This extension study did not randomize participants. All prior participants were given a single dose of MenABCWY, while all new ly enrolled participants were given two doses of MenABCWY.
Short- term immunity one month after one dose
MenABCWY vs MenACWY
Short -Term Immunity After One Dose for Healthy Persons
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Includes one study with concomitant administration of MenB; meta -analysis suggested no statistically significant subgroup differ ences.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. 16Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity vs MenACWY (follow -up: 1 month) Serogroup A
Moderate Critical
43 Randomized
trialsNot
seriousNot serious Serious4 Not serious GSK funded914 1,093 0.94 (0.86, 1.01)5,437 fewer (11,705
fewer to 832 more)
Serogroup C
926 1,105 1.03 (0.97, 1.10)2,726 more (2,545
fewer to 7,997 more)
Serogroup W
926 1,106 1.02 (1.00, 1.04)1,930 more (314 to
3,546 more)
Serogroup Y
929 1,109 0.98 (0.93, 1.03)1,930 fewer (6,528
fewer to 2,668 more)
Short -Term Immunity After One Dose for Persons at Increased Risk
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Includes one study with concomitant administration of MenB; meta -analysis suggested no statistically significant subgroup differ ences.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Studies did not include persons at increased risk.17Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity vs MenACWY (follow -up: 1 month) Serogroup A
Low Critical
43 Randomized
trialsNot
seriousNot seriousVery
serious4,5 Not serious GSK funded914 1,093 0.94 (0.86, 1.01)5,437 fewer (11,705
fewer to 832 more)
Serogroup C
926 1,105 1.03 (0.97, 1.10)2,726 more (2,545
fewer to 7,997 more)
Serogroup W
926 1,106 1.02 (1.00, 1.04)1,930 more (314 to
3,546 more)
Serogroup Y
929 1,109 0.98 (0.93, 1.03)1,930 fewer (6,528
fewer to 2,668 more)
Short- term immunity one month after
series completion
Two doses of MenABCWY vs two doses of MenB
Short -Term Immunity After Series* Completion for Healthy Persons
19*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity after series completion vs MenB series (follow -up: 1 month) fHbp
Moderate Critical
1Randomized
trialsNot
seriousNone3 Serious4 Not serious GSK funded738 707 1.01 (0.99, 1.04)1,300 more (896
fewer to 3,496 more)
NadA
734 707 0.98 (0.96, 1.00)1,800 fewer (3,526 to
74 fewer)
NHBA
738 711 0.98 (0.96,1.00)2,200 fewer (4,110 to
290 fewer)
PorA
709 684 0.91 (0.86, 0.96)7,300 fewer (11,560
to 3,040 fewer)
Short -Term Immunity After Series* Completion for Persons at Increased Risk
20*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Studies did not include persons at increased risk.Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Short -term immunity after series completion vs MenB series (follow -up: 1 month) fHbp
Low Critical
1Randomized
trialsNot
seriousNone3 Very
serious4,5 Not serious GSK funded738 707 1.01 (0.99, 1.04)1,300 more (896
fewer to 3,496 more)
NadA
734 707 0.98 (0.96, 1.00)1,800 fewer (3,526 to
74 fewer)
NHBA
738 711 0.98 (0.96,1.00)2,200 fewer (4,110 to
290 fewer)
PorA
709 684 0.91 (0.86, 0.96)7,300 fewer (11,560
to 3,040 fewer)
Long -term immunity two years after series
completion
Two doses of MenABCWY vs two doses of MenB
Long -Term Immunity After Series* Completion for Healthy Persons
22Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Long -term immunity after series completion vs MenACWY (follow -up: 2 years)
0
Long -term immunity after series completion vs MenB (follow -up: 2 years fHbp
Low Important
1Randomized
trialsNot
seriousNone3 Serious4 Serious5 GSK funded70 119 1.46 (0.84, 2.54)8,000 more (4,379
fewer to 20,379 more)
NadA
72 121 0.90 (0.77, 1.06)8,000 fewer (20,228
fewer to 4,228 more)
NHBA
71 122 1.31 (0.86, 2.00)9,000 more (4,770
fewer to 22,770 more)
PorA
71 121 1.17 (0.61, 2.22)2,000 more (9,069
fewer to 13,069 more)
*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Based on both the precision of the relative and absolute effects and the relatively small sample size
Long -Term Immunity After Series* Completion for Persons at Increased Risk
23Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
Long -term immunity after series completion vs MenACWY (follow -up: 2 years)
0
Long -term immunity after series completion vs MenB (follow -up: 2 years fHbp
Very low Important
1Randomized
trialsNot
seriousNone3 Very
serious4,5 Serious6 GSK funded70 119 1.46 (0.84, 2.54)8,000 more (4,379
fewer to 20,379 more)
NadA
72 121 0.90 (0.77, 1.06)8,000 fewer (20,228
fewer to 4,228 more)
NHBA
71 122 1.31 (0.86, 2.00)9,000 more (4,770
fewer to 22,770 more)
PorA
71 121 1.17 (0.61, 2.22)2,000 more (9,069
fewer to 13,069 more)
*MenABCWY and MenB given on a 0,6 month schedule
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider
et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26.
5Studies did not include persons at increased risk
6Based on both the precision of the relative and absolute effects and the relatively small sample size
Adverse events
Serious
Non -serious after one dose
Non -serious after ≥2 doses
Serious Adverse Events Assessed as Possibly Related to Vaccination,
Regardless of Dosing Schedule
25StudyNumber
Pentavalent MenACWY MenB MenACWY/MenB
Saez -Llorens 201510 0 -- --
Block 2015 0 0 0 --
Welsch 2018 0 0 -- --
Vesikari 20212
(seizure, connective
tissue disorder)-- 0 --
Beran 2021 0 01
(syncope)0
v72_722 1
(neuromyelitis optica)1
(pyrexia)1
(ulcerative colitis)--
MenABCWY_019 0 0 -- --
1One related event during extension study in a recipient of a MenABCWY that contained ¼ of the usual OMV component
2These were reported as related to vaccination by investigators; however, they were not considered adverse drug reactions rela ted to vaccination after GSK and independent evaluation
Serious Adverse Events Assessed as Related to Vaccination for Healthy Persons and Those at Increased
Risk
26Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
7Randomized
trialsNot
seriousNot serious Not serious Serious3GSK funded4,016
(0-2 events
per study)3,921
(0-2 events
per study)1.03 (0.30, 3.60)6 fewer (150 fewer
to 138 more)Moderate Critical
1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Based on the precision of the relative effect
4Studies did not include persons at increased risk.Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
(95% CI)Absolute effect
RD (95% CI)
per 100,000
7Randomized
trialsNot
seriousNot serious Serious4Serious3GSK funded4,016
(0-2 events
per study)3,921
(0-2 events
per study)1.03 (0.30, 3.60)6 fewer (150 fewer
to 138 more)Low CriticalHealthy Persons
Persons at Increased Risk
The a pparent directional discrepancy between RR and RD is due to a continuity correction for the RR to adjust zeros
Non -Serious Adverse Events for Healthy Persons
27Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
After one dose
4
Randomized
trialsNot
seriousvs MenB
Not serious Not serious Not serious GSK funded 2,766 2,315 1.00 (0.98, 1.02)106 more (1,434
fewer to 1,647 more)High Important
1vs MenB/MenACWY
None3 Not serious Serious4 GSK funded 100 204 0.93 (0.86, 1.00)6,588 fewer (13,337
fewer to 161 more)Moderate Important
6vs MenACWY
Not serious Not serious Serious5 GSK funded 2,683 1,190 1.97 (1.65, 2.36)42,626 more (36,291
to 48,962 more)Moderate Important
After two or more doses
2
Randomized
trialsNot
seriousvs MenB
Not serious Not serious Not serious GSK funded 1,680 2,660 1.00 (0.98, 1.02)135 more (1,837
fewer to 2,107 more)High Important
2vs MenACWY
Not serious Not serious Serious5 GSK funded 1,935 779 2.19 (1.89, 2.54)43,148 more (38,813
to 47,484 more)Moderate Important
1f >1 study included, effects and confidence intervals were derived from a random -effects meta -analysis; if one study included, effect and confidence intervals were derived using the Wald method
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Only one study included, therefore results are consistent by default.
4Based on the imprecision of the absolute effect and the relatively small sample size
5Based on the imprecision of the relative and absolute effects, despite the relatively large sample size.
Non -Serious Adverse Events for Persons at Increased Risk
28Certainty assessment No. of patients Effect1
Certainty Importance No. of
studiesStudy
designRisk of
biasInconsistency Indirectness ImprecisionOther
considerations2GSK
MenABCWYComparatorRelative effect
RR (95% CI)Absolute effect
RD (95% CI)
per 100,000
After one dose
4
Randomized
trialsNot
seriousvs MenB
Not serious Serious3Not serious GSK funded 2,766 2,315 1.00 (0.98, 1.02)106 more (1,434
fewer to 1,647 more)Moderate Important
1vs MenB/MenACWY
None4 Serious3 Serious5 GSK funded 100 204 0.93 (0.86, 1.00)6,588 fewer (13,337
fewer to 161 more)Low Important
6vs MenACWY
Not serious Serious3 Serious6 GSK funded 2,683 1,190 1.97 (1.65, 2.36)42,626 more (36,291
to 48,962 more)Low Important
After two or more doses
2
Randomized
trialsNot
seriousvs MenB
Not serious Serious3Not serious GSK funded 1,680 2,660 1.00 (0.98, 1.02)135 more (1,837
fewer to 2,107 more)Moderate Important
2vs MenACWY
Not serious Serious3 Serious6 GSK funded 1,935 779 2.19 (1.89, 2.54)43,148 more (38,813
to 47,484 more)Low Important
1f >1 study included, effects and confidence intervals were derived from a random -effects meta -analysis; if one study included, effect and confidence intervals were derived using the Wald method
2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.
3Studies did not include persons at increased risk.
4Only one study included, therefore results are consistent by default.
5Based on the imprecision of the absolute effect and the relatively small sample size
6Based on the imprecision of the relative and absolute effects, despite the relatively large sample size.
Summary of Evidence
PICO 1: Certainty PICO 2: Certainty PICO 3: Certainty
Outcome Healthy Increased Risk Healthy Increased Risk Healthy Increased Risk
Critical outcomes
Meningococcal disease
caused by serogroups A, B,
C, W, and Y-- -- -- -- -- --
Short -term immunity Moderate Low Moderate Low Moderate Low
Serious adverse events Moderate Low Moderate Low Moderate Low
Important outcomes
Interference with other
recommended vaccines
administered concurrently-- -- -- -- -- --
Non -serious adverse
eventsModerate Low Moderate Low Moderate Low
Persistent immunity Low** Very low** -- -- Low Very low
*Three options: critical, important but not critical, of limited importance for decision making; **MenB only 29
How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
30
How substantial are the undesirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
31
Do the desirable effects outweigh the undesirable effects?Benefits and Harms
Favors
interventionFavors
comparisonFavors
bothFavors
neitherVariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X X
32
What is the overall certainty of this evidence for the critical outcomes?Benefits and Harms: Short -term Immunity
No studies
foundVery low Low Moderate High
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
33
What is the overall certainty of this evidence for the critical outcomes?Benefits and Harms: Serious Adverse Events
No studies
foundVery low Low Moderate High
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
34
Values
- Does the target population feel that the desirable effects are large relative to
the undesirable effects?
- Is there important uncertainty about or variability in how much people value
the main outcome?
MenACWY Coverage among Adolescents (2023)
≥ 1 dose
among 13 yr olds85.1%
≥ 2 doses
among 17 yr olds59.7%
Pingali C et al. MMWR Morb Mortal Wkly Rep 2024.36
MenB Coverage among Adolescents (2023)
≥ 1 dose
among 17 yr olds32.4%
≥ 2 doses
among 17 yr olds12.8%
Pingali C et al. MMWR Morb Mortal Wkly Rep 2024.37
Values
Most adolescents and parents prefer a simplified
meningococcal vaccine schedule (with fewer injections and fewer visits):
–89.6% of 16–23 year- olds
–69.1% of parents
Begum S et al. Infect Dis Ther 2024 (note GSK affiliation) 38
Values
Does the target population feel that the desirable effects are large relative to the
undesirable effects?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X X
39
Values
Is there important uncertainty about or variability in how much people value the
main outcome?
Important
uncertainty
or
variability Probably
important
uncertainty
or variabilityProbably
not
important
uncertainty
or variabilityNo
important
uncertainty
or variabilityNo known
undesirable
outcomes
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
Acceptability
- Is the intervention acceptable to key stakeholders?
Combination Vaccines
CDC’s General Best Practice Guidance for Immunization and American Academy
of Pediatrics Red Book both state a general preference for combination vaccines
over separate injections of equivalent component vaccines1,2
1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP . https://www.cdc.gov/vaccines/hcp/acip- recs/general -recs/index.html
2American Academy of Pediatrics. Red Book 2024 -27 Report of the Committee on Infectious Diseases. 33rd Edition.Potential advantages Potential disadvantages
•Improved vaccine coverage rates
•Timely catch -up immunizations
•Reduced shipping and stocking costs
•Reduced costs for extra health care visits necessitated by
deferral of vaccination
•Facilitation of additional new vaccines into vaccination programs•Adverse events that might occur more frequently with
combination vaccines than with individual components
•Confusion and uncertainty about selection of vaccine
combinations and schedules for subsequent doses
•Extra doses of certain antigens in the combination product
(MenB vaccine is more reactogenic than MenACWY vaccine)
42
Preference for Fewer Injections
Adolescents prefer fewer injections due to injection site
discomfort
Parents/caregivers prefer fewer injections to reduce number of physician visits
–Parental work loss
Begum S., et al. OFID ppS515- 6. IDWeek2023 (GSK affiliation). 43
Acceptability
Is the intervention acceptable to key stakeholders?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
44
Resource use
- Is the intervention a reasonable and efficient allocation of resources?
Economic Analysis
•PICO 1: Q-P-B was found to be cost -saving relative to the current
recommendation (vs. Q -Q-B-B).
•PICO 2: P-P-N could improve health outcomes, but costs $11.3
million per QALY saved (vs. Q -Q-N).
•PICO 3: Q-P-P is cost -saving compared to Q -Q-B-B.
Q-P-P is $4.5 million per QALY saved more than Q -P-B.
46
Resource Use
Is the intervention a reasonable and efficient allocation of resources?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X*
*WG sentiment varied from no to yes 47
Equity
- What would be the impact on health equity?
Meningococcal Disease Incidence by Race―United
States, 2015–2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Race is unknown for 5-12% of cases per year00.050.10.150.20.250.30.35
2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000
Year
White Black or African American American Indian or Alaska Native Asian or Pacific Islander
49
Average Annual Meningococcal Disease Incidence by Race
among 11 –20 year olds―United States, 2015–2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Race is unknown for 6-15% of cases per year00.010.020.030.040.050.060.070.080.090.1
White Black or African
AmericanAmerican Indian or
Alaska NativeAsian or Pacific
IslanderIncidence per 100,000
50
Meningococcal Disease Incidence by Ethnicity ―
United States, 2015 –2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Ethnicity is unknown for 2 -16% of cases per year00.020.040.060.080.10.120.140.16
2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000
Year
Hispanic or Latino Not Hispanic or Latino
51
Average Annual Meningococcal Disease Incidence by Ethnicity
among 11– 20 year olds―United States, 2015– 2023*
Source: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.
Ethnicity is unknown for 3 -27% of cases per year00.010.020.030.040.050.060.070.080.09
Hispanic or Latino Not Hispanic or LatinoIncidence per 100,000
52
MenB Vaccine Availability
Counties with lower socioeconomic status (SES) had
fewer MenB doses stocked
–20 doses/100 adolescents for low SES counties
vs.
–28 doses/100 adolescents for high SES counties
Schley et al. BMC Publ Hlth 2024 (note: Pfizer affiliation)53
Equity and Shared Clinical Decision-Making
Provider or patient awareness of a SCDM recommendation is a pre-
requisite for discussions with patients and could lead to health
inequities
–Only 51% of pediatricians and 31% of family physicians reported always or
often discussing MenB vaccination
Pentavalent vaccine could potentially reduce disparities among those
who might be interested in MenB vaccination but who might not
receive clinical care that includes discussion of MenB vaccine
Gidengil et al. Vaccine 2023; Kempe et al. Pediatrics 2018. 54
Lack of MenB Vaccine Interchangeability
Lack of MenB vaccine interchangeability currently restricts
existing MenABCWY vaccine use to patients of providers stocking Pfizer MenB vaccine products
55
Equity
What would be the impact on health equity
ReducedProbably
reducedProbably
no impactProbably
increasedIncreased VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
56
Feasibility
- Is the intervention feasible to implement?
Feasibility
Challenges with insurance or financial burdens related
to pentavalent vaccine not expected
GSK pentavalent vaccine would provide additional option and may reduce number of doses for some people
Lack of MenB vaccine interchangeability complicates stocking considerations
58
Feasibility
Is the intervention feasible to implement?
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX X
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
59
EtR Domain QuestionWork Group
Determination –
PICO 1Work Group
Determination –
PICO 2Work Group
Determination –
PICO 3
Public health
problemIs invasive meningococcal disease a problem of public health importance?Yes Yes Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Small Small Small
How substantial are the undesirable anticipated effects? Minimal Small Minimal
Do the desirable anticipated effects outweigh the undesirable effects?Favors
interventionFavors intervention/
comparison/bothFavors
intervention/
comparison/both
What is the overall certainty of evidence? Low Low Low
Values Does the target population feel the desirable effects are large relative to the undesirable effects?Yes Probably yes Probably yes/yes/
don’t know
Is there important variability in how patients value the
outcome?Probably not/no Probably/probably
notProbably/probably
not
Acceptability Is the intervention acceptable to key stakeholders? Yes Probably yes Probably yes/yes
Resource use Is the intervention a reasonable and efficient allocation of
resources?Yes Probably no/varies Varies
Equity What would be the impact of the intervention on health equity?Probably
increasedProbably
increased/increasedProbably increased
Feasibility Is the intervention feasible to implement? Yes Probably yes/yes Yes
60
Balance of Consequences
Undesirable
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
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X X
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX X X
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X X X
Work Group Interpretation
Is there sufficient information to move forward with a recommendation?
Yes No
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY +
MenBX
PICO 2 (PPB vs. QQBB or PP
vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X
62
Work Group Interpretation
We do not
recommend the
interventionWe do
recommend the
intervention
PICO 1 (QPB vs. QQBB):
MenABCWY vs. MenACWY + MenBX
PICO 2 (PPB vs. QQBB or PP vs. QQ):
MenABCWY vs. MenACWYX
PICO 3 (QPP vs. QQBB):
MenABCWY vs. MenB X X
63
64Comment Regarding Work Group Interpretation
Several Work Group members noted that it would be important to
harmonize recommendations between the GSK and Pfizer pentavalent
vaccines
–Unless there is a vaccine -specific reason to have a different
recommendation
65Next Steps
An interim recommendation for the GSK vaccine could mirror the
recommendation made for the Pfizer vaccine last year
–Accept PICO 1, reject PICOs 2 and 3
Recommendations for use of both pentavalent vaccines could then be
revisited as part of future adolescent schedule deliberations if desired
66Acknowledgements
Avnika Amin
Lucy McNamara
Xiaoyu Dong
Rebecca Morgan
Doug Campos -Outcalt
Noele Nelson
Susan Hariri
LeAnne Fox
Jennifer Collins
Amy Rubis
Thank you!
67For more information, contact CDC
1-800- CDC- INFO (232- 4636)
TTY: 1 -888- 232- 6348 cdc.gov
Follow us on X (Twitter) @CDCgov & @CDCEnvironment
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f
the U. S. Centers for Disease Control and Prevention.