Document text
Evidence to Recommendations and Proposed
Recommendations: Use of Vaxelis among
American Indian and Alaska Native Infants
Jennifer Collins, MD, MSc
Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group
June 26, 2024National Center for Immunization & Respiratory Diseases
2▪Capsular polysaccharide (PRP) conjugated to carrier proteins
–Tetanus toxoid (PRP -T)
–Outer membrane protein of meningococcal serogroup B (PRP -OMP)
▪Highly immunogenic via activation of T -cell dependent immunity
–95% of infants develop protective antibody levels after a primary series
–Estimated clinical efficacy 95% ─100%
–Invasive Hib disease is uncommon in children who are fully vaccinated Haemophilus influenzae type b (Hib)
polysaccharide conjugate vaccines remain
the primary prevention strategy for Hib disease
2
3Current Hib vaccines in the United States
Vaccine Product Trade Name Primary series Booster dose
Monovalent vaccines
PRP-OMP PedvaxHIB * 2, 4 months 12–15 months
PRP-T ActHIB 2, 4, 6 months 12–15 months
PRP-T Hiberix 2, 4, 6 months 12–15 months
Combination vaccines**
DTaP -IPV/Hib Pentacel 2, 4, 6 months 12–15 months
DTaP -IPV-Hib-HepB Vaxelis 2, 4, 6 months ***
*Recommended vaccine for American Indian/Alaska Native children
**Hib component of Pentacel is PRP -T. Hib component of Vaxelis is PRP -OMP .
***Vaxelis is not recommended for the booster dose. A different Hib -containing vaccine should be administered as a booster at 12 –15 months. 3
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Briere EC, et al. Prevention and Control of Haemophilus influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR
Recommendations and Reports . 63(RR01);1- 14
The use of trade names is for identification purposes only and does not imply endorsement by CDC.PedvaxHIB (PRP-OMP) is preferentially recommended
for AI/AN infants
•Vaccination with a 2 dose primary series of a Hib vaccine that contains
PRP-OMP ( PedvaxHIB ) is preferred for AI/AN infants to provide early
protection because this vaccine produce a protective antibody response
after the first dose
•A booster dose (dose 3) of Hib vaccine is recommended at age 12
through 15 months; for the booster dose, there is no preferred vaccine
formulation
4
5Vaxelis (DTaP- IPV-Hib-HepB) does not
currently have a preferential recommendation
for AI/AN infants
Vaccine Product Trade Name PRP OMP
PRP-OMP PedvaxHIB 7.5 mcg 125 mcg
DTaP -IPV-Hib-HepB Vaxelis 3 mcg 50 mcg▪Post -dose 1 immunogenicity data not previously available
▪Lower dose of PRP -OMP than PedvaxHIB
5
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
6Policy question
Should DTaP-IPV-Hib-HepB (Vaxelis) be included with
PRP-OMP (PedvaxHIB) in the preferential
recommendation for American Indian and Alaska Native
(AI/AN) infants based on the Hib component?
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Public health problem
Is invasive Hib disease among American Indian and Alaska Native infants a
problem of public health importance?
8•Before the introduction of effective vaccines, Hib was the leading cause
of bacterial meningitis and other invasive bacterial disease in the United
States, primarily among children aged <5 years
•Most common clinical syndromes of invasive Hib disease in the post -
vaccine eraPublic health problem
Bacteremic
pneumonia
MeningitisBacteremia
without a focus
9▪Incidence of invasive Hib disease
declined >99% with introduction of
Hib vaccines
▪American Indian/Alaska Native
children aged <5 years have a 31 -
fold higher incidence of invasive Hib
disease than non -Native childrenIncidence per 100,000 of invasive Hib disease
among children aged <5 years, 2011 –2020
0123
AI/AN Non-AI/AN2.5
0.08051015202530
1980 1990 2000 2010Incidence per 100,000 of invasive Hib disease
among children aged <5 years, 1980 –2012Public health problem
10▪Is invasive Hib disease a public health problem among American Indian
and Alaska Native populations?Public health problem:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
Most common 2nd most common
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?
12PICO components
Population American Indian and Alaska Native infants
Intervention Vaxelis (DTaP -IPV-Hib-HepB )
Comparison PedvaxHIB (PRP -OMP)
Outcomes- Invasive Hib disease
- Post -dose 1 immunity
- Post -primary series immunity
- Serious adverse events
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
13GRADE evidence retrieval
Records identified and
screened
(n=2,332)
Records excluded based on title (n=2,290):
Not a Hib vaccine clinical trial (n=2,070)
Different Hib vaccine (n=191)
Did not enroll AI/AN infants (n=29)Abstracts assessed for
eligibility
(n=42) Records excluded based on abstract/full text (n=41):
Not a Hib vaccine clinical trial (n=6)
Different Hib vaccine (n=10)
Did not enroll AI/AN infants (n=16)
Other PICO components not aligned (n=9) Articles included in GRADE
(n=1)
*Search was limited to studies in English from 2014 –present based on earliest clinical trials of Vaxelis having been published in 2015. Two reviewers screened titles, abstracts and full-text records,
as indicated, to determine whether records should be included.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
14GRADE Table 2: Outcomes and Rankings
Outcome ImportanceIncluded in
evidence profile
Invasive Hib disease Important No
Post -dose 1 immunity Critical Yes
Post -primary series immunity Important Yes
Serious adverse events Critical Yes
15▪Immunity and serious adverse events assessed using data from one phase
IV, prospective, open -label randomized controlled clinical trial
–Enrolled healthy infants
•Born at gestational age ≥35 weeks
•Aged 42 –90 days at the time of first vaccination
•Identified as AI/AN by parent/legally authorized representative
–Randomized to Vaxelis vs. PedvaxHIB
•Vaxelis administered at ages 2, 4, and 6 months
•PedvaxHIB administered at ages 2 and 4 months
–Compared antibody levels before vaccination vs. day 30, 120, and 150 post -
dose 1
–Safety monitoring for serious adverse events on day 0, 30, 60, 120, and 150 Available evidence
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
16Post-dose 1 immunity
▪Anti-Hib IgG geometric mean
concentration (GMC) ratio (Vaxelis:
PedvaxHIB ) 30 days post -dose 1
met pre -specified non -inferiority
criterion
▪The proportion of infants with anti -
Hib concentration above the
putative correlate of short -term
protection 30 days post -dose 1 was
similar between groups
–Vaxelis 75.7%
–PedvaxHIB 71.2%Slide credits: Laura Hammitt’s February 2024 ACIP Presentation
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
17GRADE evidence profile: post-dose 1 immunity
Assessed via proportion with anti- Hib IgG concentration ≥0.15 µg/mL 30 days post -dose 1
Certainty assessment Summary of findings Importance
#
studiesStudy
designRisk of
biasInconsistency Indirectness Imprecision Other
considerations# patients Effect Certainty
Vaxelis
n/N
%
(95% CI)PedvaxHIB
n/N
%
(95% CI)Relative
risk
(95%
CI)Absolute risk
(95% CI)
1 RCTNot
seriousaNot
seriousNot seriousb,c,dSeriouse None 115/152
(75.7%)104/146
(71.2%)1.06
(0.93 –
1.22)4,274 more
per 100,000
(from 4,986
fewer to
15,671 more)Moderate Critical
a Similar loss to follow -up for anti -Hib IgG concentration 30 days post -dose 1: Vaxelis: 15/167 (9%), PedvaxHIB : 20/166 (12%), p=0.36. Open -label study design would not affect
immune response. Median time of post -dose 1 blood draw was similar between groups: Vaxelis 34 days (IQR 32 –37 days) versus PedvaxHIB 34 days (IQR 31 –39 days).
b Immunity is inferred from proportion with anti -Hib concentration above the putative correlate of short -term protection.
C As modeled by constrained longitudinal data analysis, anti -Hib GMC 30 days post -dose 1 for Vaxelis group (0.41; 95% CI: 0.33 –0.51) was non -inferior to that of the PedvaxHIB
group (0.40; 95% CI: 0.31 –0.50). Ratio of GMCs ( Vaxelis:PedvaxHIB ): 1.03 (95% CI: 0.75 –1.41); the pre -specified non -inferiority criterion was met based on the lower bound of
the 95% CI being >0.67.
d Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did
not warrant a downgrade.
e Downgraded because the absolute effect confidence interval is wide.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
18▪The proportion of infants with
anti-Hib concentration above the
putative correlate of long -term
protection 150 days post -dose 1
was higher in the Vaxelis group
(83.6%) than in the PedvaxHIB
group (71.7%, p<0.05)
▪Antibody titers were not
collected beyond day 150 post -
dose 1Post-primary series immunity
Slide credit: Laura Hammitt’s February 2024 ACIP Presentation
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
19GRADE evidence profile: post-primary series immunity
Assessed via proportion with anti- Hib IgG concentration ≥1.0 µg/mL 150 days post -dose 1
Certainty assessment Summary of findings Importance
#
studiesStudy
designRisk of
biasInconsistency Indirectness Imprecision Other
considerations# patients Effect Certainty
Vaxelis
n/N
%
(95% CI)PedvaxHIB
n/N
%
(95% CI)Relative
risk
(95%
CI)Absolute
risk
(95% CI)
1 RCTNot
seriousaNot
seriousNot seriousb,cSeriousd None 107/128
(83.6%)84/117
(71.8%) 1.16
(1.02 –
1.34) 11,487 more
per 100,000
(from 1,436
more to
24,410
more)Moderate Important
a Similar loss to follow -up for anti -Hib IgG concentration 150 days post -dose 1: Vaxelis 39/167 (23%), PedvaxHIB 49/166 (30%), p=0.20. Open -label study design would not
affect immune response. Median time of day 150 blood draw was similar between groups: Vaxelis 174 days (IQR 163 –187 days) versus PedvaxHIB 180 days (IQR 162 –189
days).
b Immunity is inferred from proportion with anti -Hib concentration above the putative correlate of long -term protection.
c Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did
not warrant a downgrade.
d Downgraded because the absolute effect confidence interval is wide.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
20General safety of Vaxelis (DTaP-IPV-Hib-HepB)
▪In pre -licensure clinical trials, the safety profile was consistent with that of
licensed comparator vaccines except higher rate of fever than with DTaP -IPV/Hib
(Pentacel ) (47.1% –47.4% vs. 33.2% –34.4%)1,2; rates of fever -related medical
events were similar between groups
▪Post -licensure analysis of Vaccine Adverse Event Reporting System ( VAERS) data
from June 26, 2019 – June 16, 2023 did not identify new or unexpected safety
issues
1Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.
2Block SL, et al. Lot -to-lot consistency, safety, tolerability and immunogenicity of an investigational hexavalent vaccine in U.S . infants. Pediatr Infect Dis J 2017;36:202 –8.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
21▪The frequency of SAEs was similar
between groups
–Vaxelis (5%)
–PedvaxHIB (7%)
▪The most common SAE was acute
respiratory infection
▪No SAEs were deemed related to
study participation GRADE: Serious adverse events among
AI/AN infants in the Hibvax Study
Slide credit: Laura Hammitt’s February 2024 ACIP Presentation
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
22GRADE evidence profile: serious adverse events
Assessed via proportion with SAEsa
Certainty assessment Summary of findings Importance
#
studiesStudy
designRisk of
biasInconsistency Indirectness Imprecision Other
considerations# patients Effect Certainty
Vaxelis
n/N
%
(95% CI)PedvaxHIB
n/N
%
(95% CI)Relative
risk
(95%
CI)Absolute
risk
(95% CI)
1 RCTNot
seriousbNot
seriousNot seriouscSeriousd None9/167
(5.4%) e12/166
(7.2%)e0.75
(0.32 –
1.72)1,807
fewer per
100,000
(from
4,916
fewer to
5,205
more)Moderate Critical
a From the time of the first dose of study vaccine to the end of the last study visit (approximately 5 months).
b Similar loss to follow -up through the last study visit: Vaxelis 21/166 (13%) PedvaxHIB 16/167 (10%) p=0.37. Open -label study design may bias reporting of SAEs but WG members
determined this did not warrant a downgrade.
c Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did not
warrant a downgrade.
d Downgraded because the absolute effect confidence interval is wide.
e In the Vaxelis group 10 SAEs occurred among 9 participants. In the PedvaxHIB group, 15 SAEs occurred among 12 participants. The most common SAE was acute respiratory infection
21/25 (84%). No SAEs were deemed related to study participation.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
23GRADE Summary Table
Type Outcome ImportanceDesign
(# studies)FindingsEvidence
type*
BenefitsInvasive Hib disease n/a No data available ND
Post -dose 1
immunityCritical RCT (1)The proportion participants with anti -Hib
concentration ≥0.15 µg/mL* 30 days post -dose 1
was similar between groupsModerate
Post -primary series
immunityImportant RCT (1)The proportion participants with anti -Hib
concentration ≥1.0 µg/mL** 150 days post -dose 1
was higher in the Vaxelis group. Antibody titers
were not available beyond day 150 post -dose 1.Moderate
HarmsSerious adverse
eventsCritical RCT (1)The proportion of SAEs was similar between
groups; no SAEs were deemed related to study
participationModerate
*Putative correlate of short -term protection
**Putative correlate of long -term protection
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
24▪How substantial are the desirable anticipated effects overall and for each
main outcome for which there is a desirable effect?
▪How substantial are the undesirable effects overall and for each main
outcome for which there is an undesirable effect?Benefits and harms:
Work Group determination
Minimal Small Moderate Large Varies Don’t know
Most common 2nd most common 3rd most common MajorityMinimal Small Moderate Large Varies Don’t know
25▪Do the desirable effects outweigh the undesirable effects?
▪What is the overall certainty of evidence for the critical outcomes?Benefits and harms:
Work Group determination
Most common 2nd most common Majority Favors
intervention
(Vaxelis only)Favors
comparison
(PedvaxHIB only)Favors
both
(Vaxelis & PedvaxHIB )Favors
neitherUnclear
High Moderate Low Very low
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
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?
27▪Limited data were available
▪Vaxelis would provide an additional option for AI/AN infants
▪In collaboration with CDC’ Office of Tribal Affairs and Strategic Alliances
(OTASA), NCIRD held a listening session with tribal communities in January
2024
–80 attendees, including
•9 from tribes or tribal serving organizations
•46 from Indian Health Service (IHS)
–Key questions and concerns raised by participants for WG consideration
•Will Vaxelis offer the same protection as PedvaxHIB ?
•Need to monitor for possible breakthrough cases
•Safety and side effects Values
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
28▪Does the target population feel the desirable effects are large relative to
the undesirable effects?
▪Is there important uncertainty about, or variability in, how patients value
the outcomes?Values:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
No Probably no Probably yes Yes Varies Don’t know
Most common 2nd most common 3rd most common 4th most common Majority
Acceptability
Is the intervention acceptable to key stakeholders?
30▪Limited data were available
▪Vaxelis would reduce the number of injections to complete the childhood
immunization series for those who receive it and may therefore improve
acceptability for parents/guardians and medical providers
▪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
–Considerations should include provider assessment, patient preference,
and the potential for adverse events.1
▪Proposed policy option to add Vaxelis retains flexibility for providers to
continue using PedvaxHIBAcceptability
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 2018 Report of the Committee on Infectious Diseases. 31st Edition.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
31General best practice guidance for
immunization: combination vaccines
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
1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html
32▪Is the intervention acceptable to key stakeholders?
–Are there key stakeholders that would not accept the distribution of
benefits, harms, and costs?
–Are there key stakeholders that would not accept the costs or
undesirable effects in the short term for the desirable effects in the
future?Acceptability:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
Most common 2nd most common 3rd most common Majority
Resource use
- Is the intervention a reasonable and efficient allocation of resources?
34Vaxelis protects against 6 infections with fewer
injections
Pediarix is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.
DTaP is a vaccine that protects against diphtheria, tetanus, and pertussis. The 4th dose of DTaP is recommended at age 15 –18 months.
IPV is inactivated polio vaccine.Option 2 months 4 months 6 months 12–15
monthsTotal shots
1 Vaxelis Vaxelis Vaxelis PedvaxHIB
DTaP5
2 PedvaxHIB
PediarixPedvaxHIB
Pediarix PediarixPedvaxHIB
DTaP7
3 PedvaxHIB
DTaP
IPV
HepBPedvaxHIB
DTaP
IPVDTaP
IPV
HepBPedvaxHIB
DTaP12
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
35Pediatric/Vaccines for Children (VFC) Vaccine Price List
Pediarix is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.
DTaP is a vaccine that protects against diphtheria, tetanus, and pertussis.
IPV is inactivated polio vaccine.Vaccine Trade name CDC cost/dose Private sector
cost/dose
DTaP -IPV-Hib-HepB Vaxelis $100.59 $150.85
PRP-OMP PedvaxHIB $16.14 $29.71
DTaP -HepB -IPV Pediarix $66.07 $97.97
DTaPDaptacel $21.69 $29.31
Infanrix $21.66 $28.80
IPV IPOL $16.46 $42.64
HepBEngerix B $17.38 $28.42
Recombivax HB $14.59 $27.12
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
36Estimated cost of vaccine options that protect against
the 6 pathogens in Vaxelis
*Vaccine cost ranges reflect different costs for DTaP ( Daptacel vs. Infanrix) and HepB (Engerix B vs. Recombivax HB).
**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for inflation.1 A factor of 0.6 was used to calculate the p rivate sector
administration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3
1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917
2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011
3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.OptionVaccines
(# doses to complete
childhood series)Total CDC cost
(vaccines only*)Total CDC cost
(vaccines + admin**)Total private sector cost
(vaccines only*)Total private sector cost
(vaccines + admin**)
1Vaxelis (3)
$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB (1)
DTaP (1)
2Pediarix (3)
$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB (3)
DTaP (1)
3PedvaxHIB (3)
$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)
IPV (3)
HepB (2)
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
37OptionVaccines
(# doses to complete
childhood series)Total CDC cost
(vaccines only*)Total CDC cost
(vaccines + admin**)Total private sector cost
(vaccines only*)Total private sector cost
(vaccines + admin**)
1Vaxelis (3)
$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB (1)
DTaP (1)
2Pediarix (3)
$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB (3)
DTaP (1)
3PedvaxHIB (3)
$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)
IPV (3)
HepB (2)Vaccine only costs are higher for option 1
(i.e., using Vaxelis)
*Vaccine cost ranges reflect different costs for DTaP ( Daptacel vs. Infanrix) and HepB (Engerix B vs. Recombivax HB).
**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for inflation.1 A factor of 0.6 was used to calculate the p rivate sector
administration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3
1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917
2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011
3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
38OptionVaccines
(# doses to complete
childhood series)Total CDC cost
(vaccines only*)Total CDC cost
(vaccines + admin**)Total private sector cost
(vaccines only*)Total private sector cost
(vaccines + admin**)
1Vaxelis (3)
$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB (1)
DTaP (1)
2Pediarix (3)
$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB (3)
DTaP (1)
3PedvaxHIB (3)
$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)
IPV (3)
HepB (2)Total costs are similar accounting for administration
costs
*Vaccine cost ranges reflect different costs for DTaP ( Daptacel vs. Infanrix) and HepB (Engerix B vs. Recombivax HB).
**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for inflation.1 A factor of 0.6 was used to calculate the p rivate sector
administration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3
1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917
2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011
3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
39▪Cost is similar for Vaxelis and other vaccine options that cover the same
pathogens, accounting for administration costs
▪Resource use has been acceptable for the general U.S. population;
equitable to use the same standard for AI/AN childrenResource use (summary)
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
40▪Is using Vaxelis among American Indian and Alaska Native infants a
reasonable and efficient allocation of resources?Resource use:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
The use of trade names is for identification purposes only and does not imply endorsement by CDC.Most common 2nd most common 3rd most common Majority
Equity
- What would be the impact on health equity?
42▪Limited data were available
▪The option to use a combination vaccine may improve equity by
–Improving reliability of the vaccine supply
–Improving Hib vaccination uptake among AI/AN populations, who
are disproportionately at risk for invasive Hib diseaseEquity
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
43▪What would be the impact of using Vaxelis among American Indian and
Alaska Native infants on health equity? Equity:
Work Group determination
Minimal* Small Moderate Large** Varies Don’t know
*Would not reduce disparities
**Would greatly reduce disparities
Most common 2nd most common 3rd most common 4th most common Majority
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Feasibility
- Is the intervention feasible to implement?
45▪Widely used in the general U.S. population with >7.4 million doses distributed in the United
States (as of Q1 2024)1
▪Adding Vaxelis to the preferential recommendation for AI/AN infants would
–Increase flexibility for patients and providers
–Reduce the number of injections to complete the childhood immunization series for those who
receive it
▪Neither Vaxelis nor PedvaxHIB require reconstitution
▪Shelf life of Vaxelis (4 years) is longer than that of PedvaxHIB (3 years)
▪Vaxelis cannot be used for the booster dose; clinics will need to stock additional products
–Stocking PRP -OMP ( PedvaxHIB ) for the Hib booster dose would maintain parent/guardian and
provider flexibility to choose this for doses 1 –3
–Stocking PRP -T is also an option
•Vaxelis primary series with a heterologous booster (PRP -T) was shown to produce a robust
immune response in a small study2
•Risk of inadvertent administration of PRP -T for doses 1 –3 with a less robust immune
response following doses 1 and 2Feasibility
1Per the manufacturer
2Wilck et al. Vaccine . 2021;39(9):1428- 1434.
The use of trade names is for identification purposes only and does not imply endorsement by CDC.
46▪Is using Vaxelis among American Indian and Alaska Native infants feasible
to implement?Feasibility:
Work Group determination
No Probably no Probably yes Yes Varies Don’t know
The use of trade names is for identification purposes only and does not imply endorsement by CDC.Most common 2nd most common Majority
Summary
EtR Domain Question Work group
determination
Public health problem Is invasive Hib disease among American Indian and Alaska Native children a problem of
public health importance?Yes
Benefits and harms How substantial are the desirable anticipated effects? Moderate
How substantial are the undesirable anticipated effects? Minimal
Do the desirable anticipated effects outweigh the undesirable effects? Favors both
(Vaxelis & PedvaxHIB )
What is the overall certainty of the evidence for the critical outcomes? Moderate
Values Does the target population feel the desirable effects are large relative to the undesirable
effects?Probably yes or yes
Is there important variability in how patients value the outcome? Probably no, probably
yes or don’t know
Acceptability Is the intervention acceptable to key stakeholders? Probably yes
Resource use Is the intervention a reasonable and efficient allocation of resources? Yes
Equity What would be the impact of the intervention on health equity? Moderate
Feasibility Is the intervention feasible to implement? Yes
48The use of trade names is for identification purposes only and does not imply endorsement by CDC.Favorable Uncertain
49Balance of Consequences
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
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
Most common 2nd most common Majority of WG members think desirable consequences probably
outweigh undesirable consequences in most settings
Is there sufficient information to move forward with a recommendation?
Yes No
49
50Most common 2nd most common Work Group Interpretation:
Should DTaP-IPV-Hib-HepB (Vaxelis) be included with PRP-OMP
(PedvaxHIB) in the preferential recommendation for American
Indian and Alaska Native infants based on the Hib component?
We do not recommend the intervention
We recommend the intervention
Majority of WG members favored recommending the intervention
50The use of trade names is for identification purposes only and does not imply endorsement by CDC.
51ACIP recommends DTaP-IPV-Hib-HepB (Vaxelis®) should be included with
PRP-OMP (PedvaxHIB®) in the preferential recommendation for American
Indian and Alaska Native infants based on the Haemophilus influenzae
type b (Hib) Hib component.Draft proposal language
51The use of trade names is for identification purposes only and does not imply endorsement by CDC.
Acknowledgments
▪ ACIP Members on the WG
– Jamie Loehr (Chair)
– Wilbur Chen
▪ Ex Officio WG Members
– Margaret Bash (FDA)
– Matthew Clark (IHS)
– Xin-Xing Gu (NIH)
▪ WG Liaisons and Consultants
– Amra Resic (AAFP)
– Mary Healy (AAP)
– Barb Fluty (ACHA)
– Karyn Lyons (AIM)
– Paul Cieslak (CSTE)
– Kathy Hsu (IDSA)
– Pamela Doyon -Plourde (NACI)
– Jeff Goad (NFID)
– Jessica Cataldi (PIDS)
– Amy Middleman (SAHM)
– Kathy Poehling (Wake Forest)
– Lynn Bahta (Minnesota Department of Health)
– David Stephens (Emory)▪ CDC Contributors
– Lucy McNamara (DBD/NCIRD)
– Sarah Schillie (DBD/NCIRD)
– LeAnne Fox (DBD/NCIRD)
– Susan Hariri (DBD/NCIRD)
– Veronica Pinell -McNamara (DBD/NCIRD)
– Amy Rubis (DBD/NCIRD)
– Gabrielle Cooper (DBD/NCIRD)
– Noele Nelson (DBD/NCIRD)
– Alison Albert (DBD/NCIRD)
– Angela Jiles (DBD/NCIRD)
– Shelby Miller (DBD/NCIRD)
– Marc Fischer (DIDRI/NCEZID)
– Jonathan Duffy (DHQP/NCEZID)
– Pedro Moro (DHQP/NCEZID)
– Tanya Myers (DHQP/NCEZID)
– Liz Velazquez (ISD/NCIRD)
– Jessica MacNeil (ACIP Secretariat)
– Hannah Rosenblum (ACIP Secretariat)
– Melinda Wharton (ACIP Secretariat)
▪ GRADE/ EtR Support
– Doug Campos -Outcalt (Arizona)
– Rebecca Morgan (Case Western Reserve) 52
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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.
53