Document text
Centers for Disease Control and Prevention
Evidence to Recommendations Framework
Respiratory Syncytial Virus (RSV) in Adults
GSK adjuvanted RSVpreF3 vaccine in older adults
Pfizer bivalent RSVpreF vaccine in older adults
Michael Melgar, MD
Lead, Adult RSV ACIP Work Group ACIP Meeting February 23, 2023
Evidence to Recommendations (EtR ) Framework
Poli
cy Questions
Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥65 years?
Should v
accination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥60 years?
Should v
accination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥65 years?
Should vaccination with Pfizer bivalent RS VpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥60 years?
2
Evidence to Recommendations (EtR ) Framework
EtR Domain Question(s)
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?
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?
Feasibility Is the intervention feasible to implement?
Resource Use Is the intervention a reasonable and efficient allocation of resources?
Equity What would be in the impact of the intervention on health equity?
3
Evidence to Recommendations (EtR ) Framework
EtR Domain
Public Health Prob lem
Benefits and Harms
Values Acceptability Feasibility Resource Use Equity Data on RSV in older adults will be presented
4
Evidence to Recommendations (EtR ) Framework
EtR Domain
Public Health Problem
Benefits and Harms
Values
Acceptability
Feasibility
Resource Use
Equity Use of RSV vaccines broadly will be presented
5
Evidence to Recommendations (EtR ) Framework
EtR Domain
Public Health Problem
Benefits and Harms
Values
Acceptability
Feasibility
Resource Use
Equity Manufacturer- specific data will be presented
6
Public Health Problem
Is RSV among older adults of public health importance?
Among adults ≥65 years of
age in the United States,
RSV is associated with*…
*There is substantial uncertainty
in burden of disease, reflected in
wide ranges here.
6,000– 10,0001–3
deaths/year
60,000 –160,0004–8
hospitalizations/year
0.9–1.4 million5
medical encounters/year
5. McLaughlin et al, Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300
6. Zheng et al, Pneumonia (2022): https://doi.org/10.1186/s41479- 022-00098 -x
7. Branche et al, Clinical Infect Dis (2022): https://doi.org/10.1093/cid/ciab595
8. CDC RSV -NET data 2016– 2020 (unpublished) 1. Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179
2. Matias et al, Influenza Other Respi Viruses (2014): https://doi.org/10.1111/irv.12258
3. Hansen et al, JAMA Network Open (2022):
https://doi.org/10.1001/jamanetworkopen.2022.0527
4. Widmer et al, JAMA Network Open (2012): https://doi.org/10.1093/infdis/jis309 8
0 50 100 150 200 250 300 350 Hospitalizations per 100,000 237 to 325
42 to 53
7 to 11 26 to 36 50 to 67 69 to 84 111 to 133
18-49 yr 50-59 yr 60-64 yr 65-69 yr 70-79 yr 80+ yr Overall
2016-17 2017-18 2018-19 2019-20
RSV-associated hospitalization rates by adult age group,
RSV-NET 2016–2020
RSV-NET: unpublished data; https://www.cdc.gov/rsv/research/rsv-net/overview-methods.html.
Rates are adjusted for the frequency of RSV testing during recent prior seasons and the sensitivity of RSV diagnostic tests.. Slide credit: Fiona Havers 9
25 23
20 20 18
15
5 10
5 31
0
18-49 50-64 ≥65
Age group (years)
ICU admission Death
Slide credit: Fiona Havers Percent
Outcomes among adults ≥18 years hospitalized for
RSV: RSV -NET 2017–18 to 2019–20 seasons (n=8,214)
Severe outcomes
frequent among adults of all ages hospitalized for RSV
10
Adults with certain underlying medical conditions are
at higher risk of RSV hospitalization
Immune compromise, especially hematopoietic stem cell transplant and
solid organ transplant
Cardiovascular disease (e.g., congestive heart failure)
Diabetes mellitus
Chronic obstructive pulmonary disease (COPD)
Asthma
1. Anderson et al, Diagn Microbiol Infect Dis (2016): https://doi.org/10.1016/j.diagmicrobio.2016.02.025
2. Prasad et al, Clin Infect Dis (2020): https://doi.org/10.1093/cid/ciaa730
3. Kujawski et al, Plos One (2022): https://doi.org/10.1371/journal.pone.0264890
4. Branche et al, Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595 11
Summary
RSV is a frequent, often unrecognized, cause of severe respiratory
illness, with incidence increasing with age among older adults
High proportion of those hospitalized with RSV have severe outcomes, including ICU admission and death
Death is more common with increasing age
12
Public Health Problem- Work Group Interpretation
Is RSV disease of public health importance among adults aged ≥65
years?
No Prob
ably
No Pro
bably
Yes Ye
s Va
ries Don
’t
know
13
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?
Benefits and Harms
GSK adjuvanted RSVpreF3 vaccine
– Grading of Recommendations, Assessment, Development and
Evaluation ( GRADE) Summary
– Number-needed-to -vaccinate (NNV) analysis
Pfizer bivalent RSVpreF vaccine
– GRADE Summary
– NNV analysis
15
16
GRADE Framework: PICO Question
Population
Intervention
Comparison
Outcomes Persons aged ≥60 years
GSK RSVpreF3 vaccine (120 μg antigen + AS01E adjuvant, 1 dose IM)
-or-
Pfi
zer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM)
No RSV vaccine
RS
V lower respiratory tract illness/disease (LRTI/LRTD)
Medically attended RSV LRTI/LRTD
Hospitalization for RSV respiratory illness
Severe RSV respiratory illness requiring supplemental O2 or other
respiratory support
Death due to RSV respiratory illness
Serious Adverse Events (SAEs)
Inflammatory neuropathy (e.g., Guillain -Barré syndrome)
Reactogenicity (grade ≥3)
GRADE: GSK adjuvanted RSVpreF3
17
GSK, Benefits: vaccine efficacy estimates
Outcome Importance Data sources Vaccine efficacy estimatea
(95% confidence interval) Concerns in certainty
assessment
Benefits
RSV Lower Respiratory Tract Disease (LTRD) Critical
One phase 3 RCTb 82.5% (60.9%, 92.1%) Indirectness (serious)c
Medically attended RSV LRTD Critical One phase 3 RCTb 87.5% (58.4%, 96.2%) Indirectness (serious)c
Hospitalization for RSV respiratory illness Important
One phase 3 RCTb Unable to evaluated
Severe RSV respiratory illness requiring O2/respiratory support Important
One phase 3 RCTb Unable to evaluatee
Death due to RSV respiratory illness Important One phase 3 RCTb Unable to evaluatef
RCT: Randomized control trial
a Efficacy estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial int erim analysis. Data provided by manufacturer.
Efficacy was calculated as 1 – relative risk. Events of each outcome were included if they occurred on or after day 15 after injection.
b Papi A, Ison MG, Langley JM, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604
c Underrepresentation of adults aged ≥80 years, exclusion of persons with immune compromise.
d Three RSV -associated hospitalizations occurred in the modified exposed set up to the data lock point for the interim analysis. Information was not provided by study arm
(intervention vs. placebo) to avoid unblinding of cases.
e 31 cases of LRTD requiring oxygen supplementation were identified; 4 of the 31 cases were associated with RSV. All 4 cases oc curred in the placebo arm. Measures of
relative and absolute risk were not calculated due to small number of events.
f No RSV -associated deaths were recorded in the interim analysis. 18
GSK, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT,
one phase 1/2 RCT 1.03 (0.92, 1.17) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 4.10 (1.99, 8.45) None serious
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial interim analysis ( Papi A, et al. NEJM
2023 https://doi.org/10.1056/nejmoa2209604), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022
https://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer.
b No events recorded in studies included in GRADE. One event of Guillain- Barré syndrome recorded in a recipient of the investigational vaccine in an open label trial without a
placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.
19
GSK, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT,
one phase 1/2 RCT 1.03 (0.92, 1.17) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 4.10 (1.99, 8.45) None serious
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial interim analysis ( Papi A, et al. NEJM
2023 https://doi.org/10.1056/nejmoa2209604), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022
https://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer.
b No events recorded in studies included in GRADE. One event of Guillain- Barré syndrome recorded in a recipient of the investigational vaccine in an open label trial without a
placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.
Total of 1 case of inflammatory neuropathy among approximately
15,000 investigational vaccine recipients across all clinical trials 20
Summary of GRADE for GSK RSVPreF3 vaccine in older adults
Outcome Importance Design
(# of studies)Findings Evidence type
Benefits
RSV Lower Respiratory Tract
Disease (LTRD) Critical RCT (1) GSK RSVpreF3 likely reduces RSV LRTD. Moderate
Medically attended RSV LRTD Critical RCT (1) GSK RSVpreF3 likely reduces medically attended RSV LRTD. Moderate
Hospitalization for RSV respiratory illness Important RCT (1) Only three events, unknown whether in vaccine or placebo arm Unable to
evaluate
Severe RSV respiratory illness requiring O2/respiratory support Important RCT (1) Measures of relative and absolute risk not calculated due to small number of events. Unable to
evaluate
Death due to RSV respiratory illness Important RCT (1) No events observed Unable to
evaluate
Harms
Serious adverse events Critical RCT (2) GSK RSVpreF3 results in little to no differences in SAEs. High
Inflammatory neuropathy Important RCT (2) No events observed in placebo -controlled trials. Single case
observed in an open- label uncontrolled study. Unable to
evaluate
Reactogenicity (grade ≥3) Important RCT (2) GSK RSVpreF3 increases severe reactogenicity events. High
21
Summary of GRADE for GSK RSV vaccine in older adults
Overall evidence rating: Moderate certainty 22
Number needed to vaccinate (NNV): GSK RSVpreF3
Derived from cost effectiveness analysis performed by U. Michigan
Time horizon: one year
Number of vaccinations
required to prevent… Adults aged ≥65 years Adults aged ≥60 years
1 RSV outpatient visita 84 vaccinations 90 vaccinations
1 RSV hospitalizationb 1,097 vaccinations 1,348 vaccinations
1 RSV deathc 21,442 vaccinations 27,284 vaccinations
a Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) (unadjusted for RSV under -detection by NP swab RT-PCR). Vaccine efficacy (VE) against
this outcome assumed to be equal to that against medically attended acute respiratory illness (ARI) caused by RSV (GSK AReSVi-006 trial, unpublished).
b Incidence rates of RSV hospitalization taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated hospitalization assumed to be equal to that against medically attended
lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished).
c Probability of in-hospital death among adults hospitalized for RSV taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated death assumed to be equal to that against
medically attended lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished). 23
Benefits and Harms GSK adjuvanted RSVpreF3 vaccine
How substantial are the desirable anticipated effects among adults
ag
ed ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated protective effect against:
• R
SV lower respiratory tract disease (LRTD)
• Medically attended RSV LRTD
• Hospitalization for RSV respiratory illness
• Severe RSV respiratory illness requiring supplemental O2/respiratory
support
• Death due to RSV respiratory illness
Minimal Small Moderate Large Varies Don’ t know
24
Benefits and Harms GSK adjuvanted RSVpreF3 vaccine
How substantial are the undesirable anticipated effects among
ad
ults aged ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated effect on:
• S
erious Adverse Events (SAEs)
• Inflammatory neuropathy (e.g., Guillain- Barré Syndrome)
• Reactogenicity (grade ≥3)
Minimal Small Mode rate Large Varies Don’t know
Minority opinion 25
Benefits and Harms GSK adjuvanted RSVpreF3 vaccine
Do the desirable effects outweigh the undesirable effects among
adu
lts aged ≥65 years?
– What
is the balance between the desirable effects relative to
the u
ndesirable effects?
Favors intervention (GSK RSVpreF3 vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
Minority opinion 26
GRADE: Pfizer bivalent RSVpreF
27
Pfizer, Benefits: vaccine efficacy estimates
Outcome Importance Data sources Vaccine efficacy estimatea
(95% confidence interval) Concerns in certainty
assessment
Benefits
RSV Lower Respiratory Tract Illness (LRTI)
b Critical One phase 3 RCT 85.7% (37.9%, 98.4%) Indirectness (serious)c
Medically attended RSV LRTIb Critical One phase 3 RCT 80.0% (6.3%, 97.9%) Indirectness (serious)c
Hospitalization for RSV respiratory illness Important Counts not
provided Unable to evaluated
Severe RSV respiratory illness
requiring O2/respiratory support Important Counts not
provided Unable to evaluated
Death due to RSV respiratory illness Important One phase 3 RCT Unable to evaluatee
RCT: Randomized control trial
a Efficacy estimates were independently calculated using counts of events and person- time observation in the Pfizer pivotal phase 3 trial interim analysis. Data provided by
manufacturer. Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or a fter day 15 after injection.
b Pfizer pivotal phase 3 trial included co -primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In
GRADE, the outcome of LRTI with ≥3 lower respiratory signs or symptoms was used.
c Underrepresentation of adults aged ≥80 years, exclusion of persons with immune compromise.
d Counts of event were not provided by manufacturer.
e No RSV -associated deaths were recorded in the interim analysis. 28
Pfizer, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT
one phase 1/2 RCT 1.01 (0.88 to 1.16) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 1.47 (0.88 to 2.46) Imprecision (serious)c
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phas e 3 trial interim analysis, as well as from a
placebo- controlled phase 1/2 formulation selection study ( Falsey A, et al. J Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611p ). Data provided by manufacturer.
b In the Pfizer pivotal phase 3 trial interim analysis, 2 events of Guillain -Barré syndrome were recorded in the intervention arm , compared with zero in the placebo arm. No
events were recorded in the phase 1/2 formulation selection study. Measures of relative and absolute risk were not calculated due to small number of events.
c 95% confidence interval for measure of absolute risk included potential for both benefit and harm.
29
Pfizer, Harms: relative risk
Outcome Importance Data sources Relative risk estimatea
(95% confidence interval) Concerns in certainty
assessment
Harms
Serious adverse events (SAEs) Critical One phase 3 RCT
one phase 1/2 RCT 1.01 (0.88 to 1.16) None serious
Inflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb
Reactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 1.47 (0.88 to 2.46) Imprecision (serious)c
RCT: Randomized control trial
a Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phas e 3 trial interim analysis, as well as from a
placebo- controlled phase 1/2 formulation selection study ( Falsey A, et al. J Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611p ). Data provided by manufacturer.
b In the Pfizer pivotal phase 3 trial interim analysis, 2 events of Guillain -Barré syndrome were recorded in the intervention arm , compared with zero in the placebo arm. No
events were recorded in the phase 1/2 formulation selection study. Measures of relative and absolute risk were not calculated due to small number of events.
c 95% confidence interval for measure of absolute risk included potential for both benefit and harm.
Total of 2 cases of inflammatory neuropathy among approximately
26,000 investigational vaccine recipients across all clinical trials 30
Summary of GRADE for Pfizer RSV vaccine in older adults
Outcome Importance Design
(# of studies)Findings Evidence type
Benefits
RSV Lower Respiratory Tract
Illness (LRTI) Critical RCT (1) Pfizer RSVpreF likely reduces RSV LRTI. Moderate
Medically attended RSV LRTI Critical RCT (1) Pfizer RSVpreF likely reduces medically attended RSV LRTI. Moderate
Hospitalization for RSV respiratory illness Important No data Unable to
evaluate
Severe RSV respiratory illness requiring O2/respiratory support Important No data Unable to
evaluate
Death due to RSV respiratory illness Important RCT (1) No events observed Unable to
evaluate
Harms
Serious adverse events (SAEs) Critical RCT (2) Pfizer RSVpreF results in little to no difference in SAEs. High
Inflammatory neuropathy Important RCT (2) Measures of relative and absolute risk not calculated due to
small number of events. Unable to
evaluate
Reactogenicity (grade ≥3) Important RCT (2) Pfizer RSVpreF likely increases severe reactogenicity events. Moderate
31
Summary of GRADE for Pfizer RSV vaccine in older adults
Overall evidence rating: Moderate certainty 32
Number needed to vaccinate (NNV): Pfizer RSVpreF
Derived from cost effectiveness analysis performed by U. Michigan
Time horizon: one year
Number of vaccinations
required to prevent… Adults aged ≥65 years Adults aged ≥60 years
1 RSV outpatient visita 95 vaccinations 103 vaccinations
1 RSV hospitalizationb 1,275 vaccinations 1,567 vaccinations
1 RSV deathc 24,927 vaccinations 31,717 vaccinations
a Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) (unadjusted for RSV under -detection by NP swab RT-PCR). Vaccine efficacy (VE) against
this outcome assumed to be equal to that against medically attended acute respiratory illness (ARI) caused by RSV (Pfizer REN OIR trial, unpublished).
b Incidence rates of RSV hospitalization taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated hospitalization assumed to be equal to that against medically attended
lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished).
c Probability of in-hospital death among adults hospitalized for RSV taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated death assumed to be equal to that against
medically attended lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished). 33
Benefits and Harms Pfizer bivalent RSVpreF vaccine
How substantial are the desirable anticipated effects among adults
ag
ed ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated protective effect against:
• R
SV lower respiratory tract disease (LRTD)
• Medically attended RSV LRTD
• Hospitalization for RSV respiratory illness
• Severe RSV respiratory illness requiring supplemental O2/respiratory
support
• Death due to RSV respiratory illness
Minimal Small Moderate Large Varies Don’t know
34
Benefits and Harms Pfizer bivalent RSVpreF vaccine
How substantial are the undesirable anticipated effects among
ad
ults aged ≥65 years (relative to no RSV vaccine)?
– How substantial is the anticipated effect on:
• S
erious Adverse Events (SAEs)
• Inflammatory neuropathy (e.g., Guillain- Barré Syndrome)
• Reactogenicity (grade ≥3)
Minimal Small Mod erate Large Varies Don’t know
Minority opinion 35
Benefits and Harms Pfizer bivalent RSVpreF vaccine
Do the desirable effects outweigh the undesirable effects among
adu
lts aged ≥65 years?
– What
is the balance between the desirable effects relative to
the u
ndesirable effects?
Favors intervention (Pfizer RSVpreF vaccine)
Favors comparison (no vaccine)
Favors both
Favors neither
Unclear
Minority opinion 36
Values
Do older adults feel the desirable effects of RSV vaccination are
large relative to the undesirable effects?
Is there important variability in how older adults value the main
outcomes?
Survey of vaccination intent for an RSV vaccine among
U.S. adults aged ≥60 years
Designed to assess vaccination intentions for a hypothetical RSV vaccine
Data collection period: December 23– 31, 2022
Final sample: 586 respondents (98.7% completion rate)
GENDER RACE/ETHNICITY AGE
56.3% Female
43.7% Male or other
gender identity 74.9% N on-Hispanic White
12.4% Non- Hispanic Black
9.1% Hispanic 70.6% 60 –70 years
29.4% ≥70 years
CDC and University of Iowa/RAND survey, unpublished 38
Definitely or
probably would get vaccinated
Unsure
Definitely or probably would not
get vaccinated
39
68% of respondents said they ‘definitely’ or ‘probably’
would get vaccinated if a safe and effective FDA-
approved RSV vaccine was available
CDC and University of Iowa/RAND survey, unpublished
Definitely or
probably would get vaccinated
Unsure
Definitely or probably would not
get vaccinated
40
77% said they ‘definitely’ or ‘probably’ would get an
RSV vaccine if it were recommended by a healthcare
provider
CDC and University of Iowa/RAND survey, unpublished
% of respondents who expressed hesitancy to receive an RSV vaccine (n=378)
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
I don’t know enough about RSV
Long-term safety
Short-term safety
Cost concerns
Don’t trust an RSV vaccine
I’ve gotten too many vaccines
RSV vaccine might cause RSV
RSV vaccine might make infection worse
None of these
An RSV vaccine wouldn’t work well
Other
I don’t like needles
Not at risk of getting RSV
Would not get sick if I got RSV
Against my religious beliefs
I’ve already had RSV
No time to get vaccinated
RSV is not real 41.0%
39.4%
29.1%
13.0%
11.9%
11.1%
9.3%
9.3% 9.3%
5.8%
5.6%
5.3%
4.5%
4.2%
1.6%
0.8% 0.8%
0.5%
Lack of RSV knowledge and safety concerns were
among the top reasons for not wanting an RSV vaccine
CDC and University of Iowa/RAND survey, unpublished 41
Values
–
–Do older adults feel that the desirable effects of RSV vaccination are
lar
ge relative to the undesirable effects?
How d
o older adults view the balance of desirable versus
un
desirable effects?
Woul
d older adults feel that the benefits outweigh the harms?
No Probably no Probably Yes Yes Varies Don’t know
42
Values
Is there important uncertainty about, or variability in, how much older
ad
ults value the main outcomes?
– Is th
ere evidence that the variability is large enough to lead to
dif
ferent decisions?
Important uncertainty or variability
Probably important uncer tainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
43
Acceptability
Would recommending RSV vaccines for older adults be
acceptable to key stakeholders?
Vaccine Policy Collaborative Initiative
Survey of physicians, February–March 2017
National network of 930 primary care physicians who agreed to
participate in surveys about vaccine policy issues
– 620 physicians (67%) completed the survey
– Responses analyzed from 317 respondents (51%) who reported
caring for ≥1 adult patient with possible RSV in the preceding 12
months
Hurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine
37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031 . 45
Physician Perception of Importance of RSV as a pathogen in
the following groups of patients, United States, 2017 (n = 317)
A majority of physicians believed
that RSV was a very important pathogen in adults of any age with an immunocompromising
condition (57%) and adults aged
≥65 years with cardiopulmonary
disease (56%).
Hurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine
37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031. 46
Physician Perception of Importance of RSV as a pathogen in
the
following groups of patients, United States, 2017 (n = 317)
One third of physicians believed
that RSV was a very important pathogen in adults 50–64 years
with cardiopulmonary disease
(35%) and adults ≥65 years
without cardiopulmonary
disease (31%).
Hurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine
37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031. 47
Acceptability
Would r ecommending RSV vaccines for adults aged ≥65 years be
acceptable to key stakeholders?
– Are th
ere key stakeholders that would not accept the distribution of
bene
fits and harms?
– Are th
ere key stakeholders that would not accept the undesirable
effects in the short term for the desirable effects (benefits) in the
fu
ture?
No Probably No Probably Yes Yes Varies Don’t know
48
Feasibility
Is RSV vaccination for older adults feasible to implement?
Barriers to implementation of a novel RSV vaccine may
include:
Vaccine storage and handling requirements
Complexity of the adult vaccination schedule (including coadministration)
Financial barriers
50
51
Storage & handling requirements
GSK RSVpreF3 Pfizer RSVpreF
Supplied as single dose Supplied as single dose, or as a 5-pack or
10-pack of single- dose kits
Reconstitution required: single dose vial
of lyophilized powder (antigen component) + single dose vial of liquid (adjuvant component) Reconstitution required: single dose vial of lyophilized powder, reconstitution supplies included in kit
Both components should be refrigerated (2–8°C) in original container, protected
from light Product should be refrigerated (2–8° C) in
original container, protected from light
After reconstitution, the product should be administered within 4 hours, otherwise
discarded After reconstitution, the product should be administered within 4 hours, otherwise
discarded
Older adult routine immunization schedule is
becoming more complex
https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html
50-64 years ≥65 years
Influenza
inactivated (IIV4) or
Influenza recombinant (RIV4) 1 dose annually
Tetanus, diphtheria, pertussis
(Tdap or Td) 1 dose Tdap, then Td or Tdap booster every 10 years
Zoster recombinant
(RZV) 2 doses
Pneumococcal
(PCV15, PCV20,
PPSV23) 1 dose PCV15 followed by PPSV23
OR
1 dose PCV20 ( see notes ) 1 dose PCV15 followed by PPSV23
OR
1 dose PCV20
Potential fall or other regularly scheduled COVID -19 vaccine
Clinicians may face competing vaccine priorities 52
Time/financial barriers
Older adults without health insurance coverage may experience financial
hardship obtaining an RSV vaccine.
Financial hardship may also arise if vaccine recipients need to take time off
from work to receive an RSV vaccine, or due to post-vaccination reactogenicity.
53
Feasibility
Is the GSK adjuvanted RSVpreF3 vaccine feasible to implement among
adul
ts aged ≥65 years?
Is th
e Pfizer bivalent RSVpreF vaccine feasible to implement among adults
aged
≥65 years?
No Probably No Pr obably Yes Ye s Va ries Don’ t know
54
Resource Use
Is an RSV vaccine program for older adults a reasonable and
efficient allocation of resources?
Work group considerations
RSV vaccination for older adults could be a cost-effective intervention
There is substantial uncertainty in the net societal costs of an RSV
vaccination program for older adults, driven by:
– Uncertainty in incidence of severe RSV illness
– Uncertainty in vaccine acquisition cost
– Uncertainty in duration of protection from RSV vaccination
None of the three models incorporated medical costs of longer -term
sequelae of RSV infection (e.g., admission to skilled nursing facilities)
Vaccination of older age groups would be more cost effective than vaccination of younger age groups
56
Resource Use
Is use of GSK a djuvanted RSVpreF3 vaccine among adults aged ≥65
yea
rs a reasonable and efficient allocation of resources, compared with
no
RSV vaccine?
Is
use of Pfizer bivalent RSVpreF vaccine among adults aged ≥65
years a reasonable and efficient allocation of resources, compared with
no
RSV vaccine?
No Probably No Prob ably Yes Yes Var ies Don’t kno w
57
Equity
What would be the impact on health equity of recommending
RSV vaccines in older adults?
Incidence of RSV
hospitalization is higher among
persons in low -
income ZIP codes
Zheng Z, et al. Estimated incidence of respiratory hospitalizations attributable to RSV infections across age and socioeconom ic groups.
Pneumonia (Nathan). 2022 Oct 25;14(1):6. doi: 10.1186/s41479- 022-00098 -x. 59
Age of adults hospitalized with RSV, by race and
ethnicity, RSV -NET
N Median age, years
(interquartile range)
All 9,163 70 (58–81)
Race and ethnicity
White, non-Hispanic 5,596 73 (62–83)
Black, non-Hispanic 1,731 60 (50–70)
Hispanic 713 65 (50–77)
Asian or Pacific Islander, non-Hispanic 518 77 (64–85)
American Indian or Alaska Native, non-Hispanic 56 57 (47–71)
CDC RSV -NET data 2015–2020 (unpublished) 60
Age of adults hospitalized with RSV, by race and
ethnicity, RSV -NET
N Median age, years
(interquartile range)
All 9,163 70 (58–81)
Race and ethnicity
White, non-Hispanic 5,596 73 (62–83)
Black, non-Hispanic 1,731 60 (50–70)
Hispanic 713 65 (50–77)
Asian or Pacific Islander, non-Hispanic 518 77 (64–85)
American Indian or Alaska Native, non-Hispanic 56 57 (47–71)
CDC RSV -NET data 2015–2020 (unpublished) 61
Chronic medical conditions associated with increased risk of RSV disease
are more prevalent in U.S. adults in certain demographic groups
Heart failure Coronary heart
disease Diabetes mellitus COPD
a Asthma
Black, non-Hispanic
b ↑c ↑↑c ↑c,d ↑e,f
AI/ANg, non -
Hispanicb ↑↑h ↑↑h ↑e
Hispanica ↑c,d,h ↓e,f
Asian, non -
Hispanicb ↓c ↓c ↑c,d ↓h ↓e
Lower income or SES
i ↑j ↑h,j,k ↑h,l ↑h ↑e,f,h
a COPD = chronic obstructive pulmonary disease
b Compared with non- Hispanic White adults
c Tsao et al, Circulation (2022): https://doi.org/10.1161/cir.0000000000001052
d Cheng et al, JAMA (2019): https://doi.org/10.1001/jama.2019.19365
e https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm
f Bhan et al, Am J Public Health (2015): https://doi.org/10.2105/ajph.2014.302172
g AI/AN = American Indian or Alaska Native h NHIS 2018: https://www.cdc.gov/nchs/nhis/shs/tables.htm
i SES = socio -economic status
j Abdalla et al, JAMA Netw Open (2020):
https://doi.org/10.1001%2Fjamanetworkopen.2020.18150
k Hamad et al, JAMA Cardiol (2020): https://doi.org/10.1001/jamacardio.2020.1458
l Beckles and Chou, MMWR (2016): http://dx.doi.org/10.15585/mmwr.mm6545a4 62
Access to an RSV vaccine may be determined by health
insurance coverage
0% 5% 10% 15% 20%
55-64 ≥65 Percentage of U.S.
adults without health
insurance
Age group (years) American Indian or Alaska Native,
non-Hispanic
Hispanic
Black, non-Hispanic
Asian, non-Hispanic
White, non-Hispanic
U.S. Census Bureau, 2021 American Community Survey 1- year estimates: https://data.census.gov/table 63
Access to an RSV vaccine may be determined by health
insurance coverage
Age group
(years) Percentage of population without health insurance
Below
poverty 1.0– 1.9x
poverty 2.0– 2.9x
poverty ≥3.0x poverty
19–64 23.0% 22.2% 16.8% 6.5%
≥65 2.3% 1.0% 0.9% 0.5%
Example income for 2 -person household $18,145 $36,290 $54,435
without children, age <65 years
U.S. Census Bureau, 2021 American Community Survey 1- year estimates: https://data.census.gov/table 64
Equity
What would be the impact on health equity of recommending RSV
vacc
ines in adults aged ≥65 years?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
65
Summary
Domain Question Work Group Judgements
Adults aged ≥65 years GSK Pfizer
Public Health
Problem Is RSV of public health importance? Yes
Benefits and
Harms How substantial are the desirable anticipated effects? Moderate – Large Moderate – Large
How substantial are the undesirable anticipated effects? Minimal – Small Minimal – Small
Do the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention
What is the overall certainty of the evidence profile? Moderate Moderate
Values Does the target population feel the desirable effects are large
relative to the undesirable effects? Yes/Probably yes
Is there important variability in how patients value the outcomes? Important variability/Probably important variability
Acceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes
Feasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes
Resource Use Is the intervention a reasonable and efficient allocation of resources? Yes/Probably yes Yes/Probably yes
Equity What would be the impact on health equity? Increased/Probably increased
67
Work Group interpretation
GSK’s adjuvanted RSVpreF3 and Pfizer’s bivalent RSVpreF vaccines both
have demonstrated significant efficacy against lower respiratory tract
illness caused by RSV among older adults
– Trials underpowered to show efficacy against RSV hospitalization
– Groups at highest risk of severe RSV disease were under- represented in
clinical trials
At least one case of inflammatory neuropathy has been observed among recipients of each investigational vaccine
If licensed, post licensure surveillance for both safety and vaccine
effectiveness will be critical
68
Choice of age threshold at which to recommend* RSV vaccines
Pros Cons
Age ≥65 years • Greater risk of RSV disease and therefore
more favorable population- wide balance
of risks and benefits of vaccination (in light of 1– 2 cases of inflammatory
neuropathy observed)
• Aligns with licensure for adjuvanted and high- dose influenza vaccines and age -
based pneumococcal vaccination • Lost opportunity to prevent additional disease in the 60–64 age group, who are
disproportionately from racial and ethnic groups impacted by RSV at earlier ages
Age ≥60 years • Potential to prevent a greater total burden of disease (e.g., number of hospitalizations)
• Increases access to adults 60 –64 with
medical risk factors for severe RSV disease (disproportionately in racial and ethnic groups impacted by RSV at earlier ages) • Uninsured adults would have difficulty obtaining vaccination (disproportionately aged 60–64 in racial, ethnic and socioeconomic
groups at greater risk)
• May experience more difficulty achieving clinician adoption of the recommendation among patients 60–64
• Less efficient allocation of societal resources
*FDA has not yet completed review of safety and efficacy data for the GSK RSVpreF3 vaccine and the Pfizer RSVpreF
vaccine. ACIP recommendations would be made only if the vaccines are approved and licensed by the FDA.
69
Evidence to Recommendations Framework
Summary: Work Group Interpretations (GSK RSVpreF3)
70
Evidence to Recommendations Framework
Summary: Work Group Interpretations (GSK RSVpreF3)
Among adults aged ≥65 years: Minority opinion
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
Among adults aged ≥60 years:
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
71
Evidence to Recommendations Framework
Summary: Work Group Interpretations (GSK RSVpreF3)
Type of recommendation, adults aged ≥65 years
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
Type of recommendation, adults aged ≥60 years*
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
*Minority opinion: shared clinical decision -making for individual adults aged 60– 64 years
Minority opinion 72
Evidence to Recommendations Framework
Summary: Work Group Interpretations (Pfizer RSVpreF )
73
Evidence to Recommendations Framework
Summary: Work Group Interpretations (Pfizer RSVpreF )
Among adults aged ≥65 years: Minority opinion
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
Among adults aged ≥60 years:
Balance of
consequences Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
74
Evidence to Recommendations Framework
Summary: Work Group Interpretations (Pfizer RSVpreF )
Type of recommendation, adults aged ≥65 years
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
Type of recommendation, adults aged ≥60 years*
We do not recommend the intervention
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention
*Minority opinion: shared clinical decision -making for individual adults aged 60– 64 years
Minority opinion 75
Acknowledgements
Doug Campos -Outcalt
Katherine Fleming-Dutra
Monica Godfrey
Fiona Havers
Anne Hause
Jefferson Jones
Megan Lindley
Meredith McMorrow
Rebecca Morgan
Neil Murthy
Sara Oliver
Christine Olson
Ismael Ortega Sanchez David Shay
Amanda Payne
Huong Pham
Jamison Pike
Tamara Pilishvili
Mila Prill
Lauren Roper
Diya Surie
Christopher Taylor
Evelyn Twentyman
Megan Wallace
Michael Whitaker
Patricia Wodi 76
Policy questions for ACIP
Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥65 years?
Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1
dose IM), rather than no vaccine, be recommended in persons aged ≥60 years?
Should vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥65 years?
Should vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),
rather than no vaccine, be recommended in persons aged ≥60 years?
For more information, contact CDC
1-800-CDC- INFO (232- 4636)
TTY: 1 -888- 232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.