07 RSV Adult Surie 508

Effectiveness of adult respiratory syncytial virus (RSV)
vaccines, 2023 –2024
Diya Surie, MD
Coronavirus and Other Respiratory Viruses Division
Centers for Disease Control and Prevention
June 26, 2024National Center for Immunization and Respiratory Diseases
This presentation has been
corrected. See slides 5, 6, 30,
and 32 for corrected slides. The
original slides are included at
the end of the presentation.
•Purpose of randomized vaccine trials is to answer the question:Goal of randomized vaccine trials is different from that
of observational vaccine effectiveness (VE) studies
Clemens J, et. al. Evaluating New Vaccines for Developing Countries: Efficacy or Effectiveness? JAMA.  1996;275(5) 390 –397. doi:10.1001/jama.1996.03530290060038 “Can the vaccine reduce disease caused by the target infection, safely,
under ideal conditions designed to detect a protective effect?”
•To maximize chances of detecting a protective effect, vaccine trials often:
-Enroll healthy individuals in the target population
-Minimize or exclude enrollment of individuals with comorbidities that might reduce
immuno genicity of vaccines
•Post -licensure observational VE studies are needed to assess vaccine performance in a
heterogeneous  population under routine vaccine program conditions
Limitations of RSV vaccine trials
1Papi A, et al; AReSVi -006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med . 2023;388(7):595 -608
2Walsh EE, et al; RENOIR Clinical Trial Group. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med . 2023;388(16):1465 -1477
3Critical illness is defined as intensive care unit admissions or deathRandomized
RSV vaccine trials1,2Observational
RSV VE studies
Immunocompromised patients Excluded Included
Adults aged ≥80 years <8% of participants ≥25% of included adults
Any chronic condition <52% of participants ≥94% of included adults
Endpoint or outcome Symptomatic, RSV -
associated lower
respiratory tract
diseaseRSV-associated emergency
department (ED) visits ,
hospitalization , critical
illness3
Presentation outline for observational VE studies
Observational VE studies Methods
IVY Network (CDC) Test-negative design1,2,3
VISION (CDC)
Veterans Health Administration (VHA) Target trial emulation4,5
Medicare/end stage renal disease (ESRD) patients Retrospective cohort
References for study design methods with relevant examples
1 Chua H, et. al. The Use of Test -negative Controls to Monitor Vaccine Effectiveness: A Systematic Review of Methodology. Epidemiology  2020;31:43 –64.
2 Adams K, et. al.  Vaccine effectiveness of primary series and booster doses against COVID -19-associated hospital admission in t he United States. BMJ  2022;379:e072065.
3 Thompson MG, et. al. Effectiveness of COVID -19 Vaccines in Ambulatory and Inpatient Care Settings. N Engl J Med. 2021;385:1355 –1371.
4 Hernan MA, et. al. Methods of Public Health Research – Strengthening Causal Inference from Observational Data. N Engl J Med. 202 1;385(15):1345 –48.
5 Bajema KL, et. al. Effectiveness of COVID -19 Treatment with Nirmatrelvir -Ritonavir or Molnupiravir  Among U.S. Veterans. Ann Intern Med. 2023;176(6):807 –816.
Comparison of demographic characteristics among
IVY , VISION, VHA, and Medicare/ESRD studies
IVY ,
no. (col %)VISION ,
no. (col %)VHA ,
no. (col %)Medicare/ESRD ,
no. (col %)
Characteristic Total no.
of
patientsTotal no.
of
patientsTotal no.
of
patientsTotal no.
of
patients
All patients 2,978 36,706 293,704§69,279
Median age, years (IQR) 72 (66 –80) 76 (69 –84) 76 (72 –80) 75 (70 -80)
Age group, years
60–74 1756 (59) 16,055 (44) 125,124 (43) 34,614 (50)‡
≥75 1222 (41) 20,651 (56) 168,580 (57) 34,665 (50)
Race and ethnicity
White, non -Hispanic 1867 (63) 27,057 (74) 225,713 (77) 42,157 (61)
Black, non -Hispanic  582 (20) 3,160 (9) 30,359 (10) 14,767 (21)
Hispanic or Latino, any race 335 (11) 2,789 (8) 11,302 (4) 3,983 (6)
Other race, non -Hispanic*101 (3) 3,395 (9) 5,971 (2) 8,372 (12)
Unknown†93 (3) 305 (1) 20,358 (7) -
* For VISION, “Other race, non -Hispanic” includes persons reporting non -Hispanic ethnicity and any of the following for race: Am erican Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander,
other races not listed, and multiple races; because of small numbers, these categories were combined. For IVY, “Other race, n on-Hispanic” includes Asian, American Indian or Alaska Native, and Native Hawaiian
or other Pacific Islander; because of small numbers, these categories were combined. For Medicare/ESRD, "Other race, non -Hispani c" includes Asian/Pacific Islander, non -Hispanic, Other, non -Hispanic, and
Unknown.
† For VISION, “Unknown” includes persons with missing race and ethnicity in their electronic health records. For IVY, “Unknow n” includes patients who self -reported their race and ethnicity as “Other” and those
for whom race and ethnicity were unknown. For VHA “Unknown” includes missing, unknown, or declined race or ethnicity.
§146,852 vaccinated persons were matched to 582,936 unvaccinated participants who were equally weighted to correspond to 146,8 52 matched unvaccinated participants.
‡Evaluation of Medicare fee -for-service claims data was restricted to adults aged 65 years and older.This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 45.
Comparison of clinical characteristics among IVY ,
VISION, VHA, and Medicare/ESRD studies
IVY ,
no. (col %)VISION ,
no. (col %)VHA ,
no. (col %)Medicare/ESRD ,
no. (col %)
Characteristic Total no.
of
patientsTotal no.
of
patientsTotal no.
of
patientsTotal no.
of
patients
All patients 2,978 36,706 293,704 69,279
No. of chronic medical condition categories
0 71 (2) 2,111 (6) 17,554 (6) 0 (0)
1 416 (14) 3,845 (10) 58,757 (20) 312 (<1)
2 783 (26) 15,420 (42) 83,992 (29) 1,497 (2)
3 863 (29) 15,330 (42) 73,296 (25) 9,242 (13)
≥4 845 (28) 2,111 (6) 60,106 (21) 58,228 (84)
Immunocompromised*720 (24) 8,435 (23) 32,996 (11) 17,499 (25)
Chronic lung disease†1423 (48) 17,541 (48) 88,648 (30) 38,529 (56)
Cardiovascular disease§2501 (84) 28,822 (79) 122,015 (42) 66,987 (97)
RSV vaccinated 265 (9) 3,275 (9) 146,852 (50)¶6,731 (10)
Received GSK (Arexvy) 137 (61)** 2,409 (74) 43,875 (30) 4,559 (68)
Received Pfizer (Abrysvo) 89 (39) ** 865 (36) 101,623 (69) 2,172 (32)
* Slide 41 provides definitions of immunocompromise from each network
† Slide 42 provides definitions of chronic lung disease from each network
§ Slide 43 provides definitions of cardiovascular disease from each network
¶ Each RSV -vaccinated patient was matched to up to 4 unvaccinated, equally weighted patients, resulting in 50% of matched persons having an RSV vaccination. Among match -eligible patients, 4.5% received RSV vaccination.
** Of 265 RSV vaccinated patients in IVY, 226 (85%) had known product type, which is used as the denominator for these percentag es.This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 47.
VE against RSV -associated hospitalization
among adults aged ≥60 years
IVY Network, October 1, 2023 –March 31, 2024
IVY Network —26 hospitals, 20 U.S. States
•Design : Test -negative, case -control design
•Analysis period : October 1, 2023 – March 31, 2024
•Population : Adults  aged  ≥60 years  hospitalized with acute respiratory
illness (ARI)* and RSV test results within 10 days of illness onset and 3 days
of admission
•Cases : ARI and test  positive  for RSV by NAAT or antigen test
– Co-infections with SARS -CoV-2 or influenza were excluded
• Controls : ARI and test negative  for vaccine -preventable respiratory
viruses, i.e., RSV, SARS -CoV-2 and influenza by RT -PCR†
•Vaccination data: Plausible self -report, e lectronic medical records (EMR),
state and city vaccine registries
•Vaccinated: Receipt of a single dose of either RSV vaccine (GSK or
Pfizer) ≥14 days before illness onset
•Unvaccinated : No RSV vaccination before illness onset
•Specimens: Nasal swabs  obtained on all patients for central RT -PCR testing
and whole genome sequencing
*ARI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pne umo nia, or hypoxemia ( SpO2 <92% on room air or below baseline for chronic users)
† Doll MK, et. al. Effects of Confounding Bias in Coronavirus Disease 2019 (COVID -19) and Influenza Vaccine Effectiveness Test -Negative Designs Due to Correlated Influenza and COVID -19 Vaccination Behaviors.
Clin Infect Dis. 2022;75(1):e564 –71

VE against RSV -associated hospitalization  among adults aged ≥60 years —
IVY Network, 24 hospitals, 19 US states, October 1, 2023 –March 31, 2024
Abbreviations : 95% CI = 95% confidence interval; IPVW = inverse probability of vaccination weighting; IQR = interquartile range
* Logistic regression m odels  were adjusted for age, sex, race and ethnicity, U.S. Department of Health and Human Services region, and month of admission. VE was calculated as: (1 – adjusted odds ratio) x 100%.
† For the IPVW VE estimate, propensity for vaccination was modeled with a priori  covariables,  including age, sex, race and ethnicity, site, calendar month, Charlson  Comorbidity Index (CCI), underlying medical
conditions, long -term care facility residence, numbers of outpatient visits or hospitalizations in the previous year, and social  vulnerability index (SVI) of community of residence. Weights were computed as the
inverse of the probability of vaccination. Only SVI remained unbalanced between vaccinated and unvaccinated patients after weigh ting and was included as a covariate in the final logistic regression model.GroupNo. of
vaccinated RSV
case -patients/
total (%)No. of
vaccinated RSV
control -
patients/
total  (%)Days since RSV
vaccination,
Median (IQR)Vaccine
effectiveness,
% (95% CI)
Adults ≥60 years, unweighted* 9/367 (2.5) 256/2611 (9.8) 84 (54 –125) 75 (50 –87)
Adults ≥60 years, IPVW†9/367 (2.5) 256/2611 (9.8) 84 (54 –125) 79 (56 –90)
Age group, years, unweighted*
60–74 years 4/214 (1.9) 118/1542 (7.7) 88 (57 –128) 75 (31 –91)
≥75 years 5/153 (3.3) 138/1069 (12.9) 81 (50 –123) 76 (40 –91)
0 20 40 60 80 100
Vaccine Effectiveness, % (95% CI) VE was high against RSV -associated
hospitalization and similar among adults
aged 60 –74 years and ≥75 years
VE against RSV -associated ED visits,
hospitalization, and critical illness among
adults aged ≥60 years
VISION Network, October 1, 2023 –March 31, 2024
•Design:  Test-negative design analysis
•Population:  Adults aged ≥60 years visiting a participating ED
for or hospitalized with RSV -like illness (RLI)* with RSV test
result within 10 days before or 72 hours after encounter
-Cases:   RLI with positive  RSV antigen or NAAT
-Controls:   RLI with negative RSV NAAT
•Vaccination data:  Documented by electronic health records,
state and city registries, and claims data (subset of sites)
-Vaccinated: Receipt of a single dose of either RSV vaccine (GSK or Pfizer) ≥14
days before illness onset
-Unvaccinated : No RSV vaccination before illness onset
•Covariate data:  Documented in electronic health recordsVISION Multi -Site Network of Electronic Health Records
245 emergency rooms and 230 hospitals
VISION 2.0 partners included in this analysis –
ED: HealthPartners Institute, Intermountain Healthcare, KPNC, KPCHR,
Regenstrief
Inpatient : HealthPartners Institute, Intermountain, KPNC, KPCHR, Regenstrief ,
University of Colorado
• Note: KPSC does not participate in VISION adult RSV analyses.
*≥1 ICD -10 code indicating RSV -like illness (RLI), defined as COVID -19 pneumonia, influenza pneumonia, other viral pneumonia, in fluenza disease, bacterial pneumonia, ARDS, COPD
exacerbation, asthma exacerbation,  respiratory failure, other acute lower respiratory tract infection, sinusitis, acute uppe r respiratory tract infections, acute respiratory signs and symptoms,
viral illness not otherwise specified, acute febrile illness signs and symptoms, sepsis, respiratory failure unspecified, and  RSV disease.
VE against RSV -associated ED visits , hospitalization , and critical illness among
immunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024
TotalRSV -Positive,
N (row %)Median interval
since last dose,
days (IQR)Vaccine
Effectiveness*,
% (95% CI)
RSV -associated ED visits
≥60 years
Unvaccinated (Ref) 33,491 2,645 (8) NA Ref
Vaccinated 3,030 57 (2) 67 (40 –101) 77 (70 –83)
RSV -associated hospitalization
≥60 years
Unvaccinated (Ref) 25,816 1567 (6) NA Ref
Vaccinated 2,455 35 (1) 74 (44 –109) 80 (71 –85)
RSV -associated critical Illness†
≥60 years
Unvaccinated (Ref) 24,506 257 (1) NA Ref
Vaccinated 2,425 5 (<1) 74 (44 –109) 81 (52 –92)
0 20 40 60 80 100
Vaccine Effectiveness, % (95% CI)
*Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, social  vulnerability index, site, calendar time, and
geographic region. VE was calculated as (1 -adjusted odds ratio)*100%.
† Critical illness was defined as intensive care unit admission and/or deathVE was high against RSV -associated ED
visits, hospitalization, and critical illness
VE against RSV -associated ED visits and hospitalization  by age group among
immunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024
TotalRSV -Positive,
N (row %)Median interval
since last dose,
days (IQR)Vaccine
effectiveness*,
 % (95% CI)
RSV -associated ED visits
60–74 years
Unvaccinated (Ref) 16,985 1303 (8) NA Ref
Vaccinated 1,139 23 (2) 66 (40 –100) 75 (62 –84)
≥75 years
Unvaccinated (Ref) 16,506 1342 (8) NA Ref
Vaccinated 1,891 34 (2) 69 (40 –101) 78 (69 –85)
RSV -associated hospitalization
60–74 years
Unvaccinated (Ref) 11,048 670 (6) NA Ref
Vaccinated  836 11 (1) 75 (46 –110) 81 (66 –90)
≥75 years
Unvaccinated (Ref) 14,768 897 (6) NA Ref
Vaccinated 1,619 24 (1) 74 (43 –108) 79 (68 –86)
0 20 40 60 80 100
Vaccine Effectiveness, % (95% CI)
* Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, socia l vulnerability index, site, calendar time, and
geographic region. VE was calculated as (1 -adjusted odds ratio)*100%.VE was similar among adults aged 60 –74
years and ≥75 years for both outcomes
VE against RSV -associated ED visits and hospitalization  by time since RSV vaccination
among immunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024
TotalRSV -Positive,
N (row %)Median interval
since last dose,
days (IQR)Vaccine
effectiveness*,
% (95% CI)
RSV -associated ED visits
≥60 years
Unvaccinated (Ref) 33,491 2,645 (8) NA Ref
Vaccinated 14 –59 days earlier 1,300 19 (1) 36 (26 –47) 85 (77 –91)
Vaccinated 60 –215 days earlier 1,728 37 (2) 95 (76 –119) 70 (58 –78)
RSV -associated hospitalization
≥60 years
Unvaccinated (Ref) 25,816 1567 (6) NA Ref
Vaccinated 14 –59 days earlier  934 7 (1) 37 (26 –48) 90 (79 –95)
Vaccinated 60 –215 days earlier 1,520 27 (2) 100 (79 –125) 73 (60 –82)
0 20 40 60 80 100
Vaccine Effectiveness, % (95% CI)VE point estimates decreased with
increased time since RSV vaccination with
limited follow -up time within the season
* Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, socia l vulnerability index, site, calendar time, and
geographic region. VE was calculated as (1 -adjusted odds ratio)*100%.
VE against RSV -associated ED visits and hospitalization  by RSV vaccine manufacturer
among immunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024
otalRSV -Positive,
N (row %)Median interval
since last dose,
days (IQR)Vaccine
effectiveness*,
% (95% CI)
RSV -associated ED visits
≥60 years
Unvaccinated (Ref) 33,491 2,645 (8) NA Ref
GSK (Arexvy) 2,522 47 (2) 67 (40 –99) 77 (70 –83)
Pfizer ( Abrysvo )  506 9 (2) 71 (40 –108) 79 (59 –89)
RSV -associated hospitalization
≥60 years
Unvaccinated (Ref) 25,816 1567 (6) NA Ref
GSK (Arexvy) 1,812 21 (1) 73 (43 –105) 83 (73 –89)
Pfizer (Abrysvo)  642 13 (2) 81 (48 –116) 73 (52 –85)
0 20 40 60 80 100
Vaccine Effectiveness, % (95% CI) VE was similar between GSK and
Pfizer RSV vaccines across outcomes
* Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, socia l vulnerability index, site, calendar time, and
geographic region. VE was calculated as (1 -adjusted odds ratio)*100%.
VE against RSV -associated hospitalization  among adults aged ≥60 years with
immunocompromise† by age group, October 1, 2023 –March 31, 2024
0 20 40 60 80 100
Vaccine Effectiveness, % (95% CI)
*Odds ratio was adjusted for age, race/ethnicity, sex, underlying medical conditions, social vulnerability index, site, calen dar time, and geographic region. VE was
calculated as (1 -adjusted odds ratio)*100%.
†Defined based on presence of ICD -10 code corresponding to hematologic malignancy, solid malignancy, transplant , rheumatologic/inflammatory disorders, HIV, or other
intrinsic immune condition or immunodeficiency in discharge diagnoses TotalRSV -Positive,
N (row %)Median interval
since last dose,
days (IQR)Vaccine
effectiveness*,
% (95% CI)
RSV -associated hospitalization
≥60 years
Unvaccinated (Ref) 7,615 314 (4) NA Ref
Vaccinated 820 10 (1) 72 (43 –108) 73 (48 –85)
RSV vaccines provided protection against
RSV-associated hospitalization among
people with immunocompromise
VE against documented RSV infection and RSV -
associated ED/UC or hospitalization among
adults aged ≥60 years
Veterans Health Administration (VHA), September 1, 2023 – March 31, 2024
Overall study design
▪Emulated a target randomized controlled trial of RSV vaccination (GSK [ Arexvy ] or Pfizer
[Abrysvo ]) compared with no RSV vaccination for the prevention of documented RSV infection and
RSV-associated ED/urgent care (UC) visits or hospitalization among Veterans ≥60 years
▪Enrollment: September 1 – December 31, 2023
▪Follow -up extended through March 31, 2024
▪Executed 4 monthly, nested sequential trials during the enrollment period
Nested sequential trial study design with matching
March 31, 2024
Abbreviations: CAN, Care Assessment Need; VISN, Veteran Integrated Service Network
* Cohort members who receive an RSV vaccine during a given trial month are no longer eligible for a subsequent trial month. C ohort members who remain unvaccinated,
alive, and who do not test positive for RSV through the end of a given trial month are eligible for a subsequent trial month.
† Follow -up begins on the day following the index date (date of RSV vaccination occurring anytime during a given trial month or same date for the matched unvaccinated
comparator) and extends until occurrence of the outcome, death, or end of the study period on March 31, 2024.
Data sources
▪The Department of Veterans Affairs
Corporate Data Warehouse (CDW)
integrates real -time, electronic health
record (EHR) data across all VHA
facilities
▪RSV tests were performed on
respiratory specimens within VHA
using nucleic acid amplification or
antigen testing
▪RSV vaccinations were administered
at VHA facilities or outside facilities
and recorded in the VHA EHR
VHA Network
18 regional systems of care
172 medical centers
1,138 outpatient sites of carehttps://www.va.gov/HEALTH/visns.asp
Eligibility
▪VHA enrollees ≥60 years during September 1 – December 31, 2023
▪Engaged in VHA care: ≥1 primary care encounter within 18 months prior to the first day of each
trial month
▪Excluded:
▪Missing ZIP codes
▪Any RSV vaccination prior to the first day of each trial month
▪Any positive RSV test results in the 90 days preceding the start of each trial month
Outcomes, Follow -up, and Analysis
▪Outcomes
▪Primary outcome:  Any positive RSV test result occurring from day 14 following the index date
through the end of the study period on March 31, 2024*
▪RSV-associated emergency department (ED) or urgent care encounters (UC)†
▪RSV-associated acute hospitalizations†
▪Negative outcome control:  incidence of laboratory -confirmed RSV infections 0 –13 days following
the index date
▪Vaccine effectiveness = (1 – hazard ratio) x 100
*Primary analysis is limited to matched groups in which patients did not have a positive RSV test result during days 0 –13 follow ing the index date.
†Occurring ±1 day of the eligible positive RSV test result.
Cumulative incidence of documented RSV infections and associated healthcare
events following the matched index date, September 1, 2023 –March 31, 2024
Negative
Outcome ControlDocumented RSV
Infection
RSV-associated
Acute
HospitalizationRSV-associated
ED or UC
Encounter

VE against documented RSV infection and RSV -associated
ED/UC visit or hospitalization, intention to treat*
RSV vaccination (GSK or Pfizer)
(N = 146,747)No Vaccination
(N = 146,747)
No. of
EventsFollow -up
(person -years)Incidence Rate
(events / 1000
person -years)No. of
EventsFollow -up
(person -years)Incidence Rate
(events / 1000
person -years)Vaccine
Effectiveness,
% (95% CI)
Documented RSV
infection from 14
days after index date88 51,281 1.7 (1.4 –2.1) 372.0 50,911 7.3 (6.6 –8.1) 77 (71 –81)
RSV-associated ED or
UC visit66 51,286 1.3 (1.0 –1.6) 289·3 50,929 5.7 (5.1 –6.4) 77 (71 –82)
RSV-associated
hospitalization15 51,298 0.3 (0.2 –0.5) 80·3 50,975 1.6 (1.3 –2.0) 82 (69 –89)
*Median follow -up 124 days [IQR 102 to 150 days]
VE against documented RSV infection by age and immunocompromised*
subgroups
RSV Vaccination (GSK or Pfizer) No Vaccination
NNo. of
EventsFollow -up,
person -
yearsIncidence
Rate (events/
1000 person -
years)No. of
EventsFollow -
up,
person -
yearsIncidence
Rate (events/
1000 person -
years)Vaccine
Effectiveness,
% (95% CI)
Age group
 60–69 years 28,247 17 7,4942.3
(1.3–3.6) 74.9 7,47410.0
(7.9–12.4) 78 (63 –86)
 70–79 years 82,734 47 22,2512.1
(1.6–2.8) 204.8 22,1689.2
(8.0–10.6) 77 (69 –83)
 ≥80 years 35,691 26 9,6012.7
(1.8–4.0) 93.5 9,5009.8
(8.0–12.0) 72 (59 –81)
Immunocompromised*
No135,936 71 365541.9
(1.5–2.5) 325.5 36,3549.0
(8.0–10.0) 78 (72 –83)
Yes10,639 16 27535.8
(3.3–9.4) 54.2 2,73019.9
(15.2 –25.8) 71 (52 –83)
*Immunocompromised was defined as receipt o f immunosuppressive (excluding steroids) or cancer medications within 90 days or 1 year of the index date (depending on the m edication), HIV with most
recent CD4 ≤2 years prior to index date ≤200 cells/mm3, or hematologic malignancy documented ≤2 years prior to index date.
VE against documented RSV infection by RSV vaccine manufacturer
RSV vaccination No Vaccination
NNo. of
EventsFollow -up,
person -
yearsIncidence
Rate
(events/
1000
person -
years)No. of
EventsFollow -
up,
person -
yearsIncidence
Rate (events/
1000 person -
years)Vaccine
Effectiveness,
 % (95% CI)
Vaccine product
GSK (Arexvy) 43,853 22 13,4111.6
(1.0–2.5) 94 13,3267.1
(5.7–8.6) 77 (64 –85)
Pfizer (Abrysvo) 101,542 66 25,5052.6
(2.0–3.3) 281·2 25,37611.1
(9.9–12.4) 77 (70 –82)
VE against RSV -associated hospitalization
among adults aged ≥65 years with end stage
renal disease (ESRD)
CMS Medicare Claims data, October 1, 2023 –February 24, 2024
Data source: Rebecca C. Woodruff, PhD. Chronic Conditions as Risk Factors for RSV -Associated Hospitalization. ACIP Meeting. February 29, 2024 . Available at:
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf     Adults with chronic kidney disease had a higher rate of
RSV-associated hospitalizations compared with all adults
*Data sources included Medicare Enrollment Database (EDB) and Common Medicare Environment (CME), Common Working File (CWF) an d Shared System Data (SSD) Medicare Parts A/B/D claims data, Minimum Data Set (MDS), and CDC/ATSDR Social Vulnerability
Index (SVI)
†At least 1 dialysis encounter (excluding acute kidney injury) in the 90 days before the index date (persons with end stage re nal disease receiving dialysis are eligible for Medicare benefits, regardless of age).  Investigation was underpowered to estimat e VE among
persons aged 60 -64 years with ESRD.
‡Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose administration.
§ RSV hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revision, Cli nical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at least one inpatient facility cl aim in the primary
position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with  pneumonia or acute respiratory failure outcome code
¶Death, disenrollment in Medicare parts A/B/D, enrollment in Medicare Part C, nursing home stay lasting ≥100 days, admission t o hospice facility, kidney transplant, receipt of a second RSV vaccine dose
**Hazard ratios adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and  Updated (2023 -2024 Formula) COVID -19 vaccination status.Medicare/ESRD: Overview
• Design: Retrospective cohort
• Data source:  Medicare fee -for-service claims data*
• Population:  Persons aged ≥65 with ESRD†
• Exposure: RSV vaccination‡
• Index date:  October 1, 2023
• Censoring events:
– RSV hospitalization§
– Other censoring event¶
– End of study period (February 24, 2024)
• VE = (1 - adjusted hazard ratio**) x 100%
where adjusted hazard ratio = 𝑟𝑎𝑡𝑒  𝑜𝑓 𝑅𝑆𝑉  ℎ𝑜𝑠𝑝𝑖𝑡𝑎𝑙𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑
𝑟𝑎𝑡𝑒  𝑜𝑓 𝑅𝑆𝑉  ℎ𝑜𝑠𝑝𝑖𝑡𝑎𝑙𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑢𝑛𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑
RSV hospitalizationOther Censoring Event
Unvaccinated person -time
Vaccinated person -time
10/1/2023 2/24/2024
*RSV -associated hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revi sion, Clinical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at
least one inpatient facility claim in the primary position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with pneumonia or acute respiratory failure outcome code.
†Defined as having at least one dialysis encounter (excluding acute kidney injury) in the 90 days preceding the index date. Pe rsons with end stage renal disease receiving dialysis are eligible for Medicare benefits, regardless of age.
§At least 2 encounters with a discharge diagnosis for an immunocompromising condition (hematologic malignancy, solid tumor mal ignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune conditions or
immunodeficiency) within 183 days before the index date.
¶A single beneficiary can contribute follow -up time in multiple categories.
**Adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and Updated (2023 -2024 Formula) COVID -19 vaccination status. VE was calculated as (1 − adjusted hazard ratio) x 100%.
††Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose
administration.
§§ Centers for Medicare & Medicaid Services (CMS) cell suppression policy limits the minimum cell size.
¶¶Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point
estimate shown, and estimates should therefore be interpreted with caution.Medicare/ESRD: VE against RSV -associated hospitalization* among adults aged ≥65
years with ESRD†, by immunocompromise status§,  October 2023 –February 2024
Immunocompromise status |
vaccination status# of
Beneficiaries# of
OutcomesMedian
Follow -up
Time (Days) ¶Vaccine Effectiveness,
% (95% CI)**
Without  Additional Immunocompromise
Unvaccinated (Ref) 47,177 342 146 Ref
Vaccinated†† 4,603 <11§§ 91 72 (41 -87)
With  Additional Immunocompromise
Unvaccinated (Ref) 15,371 161 146 Ref
Vaccinated 2,128 <11§§ 90 83 (45 -95) ¶¶
0 50 100
Vaccine Effectiveness, % (95% CI)RSV vaccination provided protection
against RSV -associated hospitalization
among adults with ESRD on dialysisThis slide contains corrections. To see the slide as originally presented, without corrections, please see slide 49.
Summary
Outcome Analysis Vaccine efficacy /effectiveness,  % (95% CI)
Symptomatic,
RSV -associated
lower
respiratory tract
disease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†83 (58 –94)
Pfizer trial (≥2 sx LRTI, co -primary endpoint) * 67 (29 –86)
Pfizer trial (≥3 sx LRTI, co -primary endpoint) * 86 (32 –99)
RSV -associated
hospitalizationIVY Network, adults ≥60 years§75 (50 –87)
VISION, adults ≥60 years, immunocompetent 80 (71 –85)
VHA, adults ≥60 years§82 (69 –89)
Medicare ESRD, otherwise immunocompetent, ≥65y 72 (41 -87)
VISION, immunocompromised 73 (48 –85)
Medicare ESRD, additional immunocompromise, ≥65y 83 (45 -95)Observational VE studies show RSV vaccines protect against severe RSV
disease, similar to results from trials, although endpoints differ
0 20 40 60 80 100
Vaccine effectiveness, % (95% CI)
† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 43 for detailed definitions.
* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 43 for detailed definitions.
§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; y = yearsThis slide contains corrections. To see the slide as originally presented, without corrections, please see slide 51.
Limitations of observational VE studies
•RSV vaccine uptake in these study populations was 5 –10%
-Early adopters of new vaccines may have different healthcare -seeking behaviors than the general population,
which could bias VE estimates upward*
•Multivariable adjustment and inverse -probability -of-vaccination -weighting were used
to minimize bias, but residual bias from unmeasured confounding may remain
•Definitions of immunocompromise varied across studies and studies were not powered
to assess VE for specific types of immunosuppression
•Median duration since RSV vaccination in these studies was 3 –4 months, which is
insufficient follow -up time to determine duration of RSV vaccine effectiveness beyond a
season
* Sullivan SG, et. al. Am J Epidemiol.  2016;184(5):345 –353.
•Under real -world conditions, RSV vaccination (GSK or Pfizer) provided protection
against severe RSV disease among US adults aged ≥60 years in this first season of use
•These results build on those from RSV vaccine trials in two ways:
-Provide evidence of VE against RSV -associated ED visits, hospitalizations, and critical illness
-Demonstrate protection in a population that more closely represents those at high -risk of
severe RSV disease, including
•Adults aged 75 years or older
•Adults with a composite of various immunocompromising conditions
•Adults with underlying conditions, especially cardiopulmonary disease
•Ongoing monitoring of RSV VE is needed to confirm findings from this season and
assess durability of RSV vaccine protectionConclusions
Acknowledgements
CDC
Amadea Britton
Allison Avrich Ciesla
Fatimah S. Dawood
Jennifer DeCuir
Monica Dickerson
Katherine Fleming -Dutra
Shikha Garg
Danica Gomes
Kelly Hatfield
Amber Kautz
Ruth Link -Gelles
Josephine Mak
Michael Melgar
Morgan Najdowski
Shannon Novosad
Lakshmi Panagiotakopoulos
Amanda Payne
Caitlin Ray
Emily L. Reeves
Mark W. Tenforde
Megan Wallace
Ryan Wiegand
Katherine A. Yuengling
CMS Collaborators
CMS
Alia Bayatti
Acumen
Heng -Ming Sung
Ivy Zhang
Carla Gomez Victor
Yenlin  Lai
Bradley Lufkin
Yoganand ChillarigeVISION Collaborators
Columbia University
Karthik Natarajan
HealthPartners
Malini B. DeSilva
Omobosola  O. Akinsete
Charlene E. McEvoy
Inih J. Essien
Intermountain Health
Kristin Dascomb
Tamara Sheffield
Daniel Bride
Julie Arndorfer
Kaiser Permanente
Center for Health Research
Stephanie A. Irving
Allison L. Naleway
Padma Koppolu
Kaiser Permanente
Northern California
Nicola P. Klein
Bruce Fireman
Ousseny  Zerbo
Julius Timbol
Kristin Goddard
Regenstrief
Shaun J. Grannis
Brian E. Dixon
William F. Fadel
Colin Rogerson
Katie AllenVA Collaborators
Grant Huang
Mihaela  Aslan
Kristina L. Bajema
George N. Ioannou
Lei Yan
Yuli Li
Stephanie Argraves
Nallakkandi  Rajeevan
Alexandra Fox
Robert Vergun
Kristin Berry
David Bui
Yuan Huang
Hung -Mo Lin
Denise Hynes
Cynthia Lucero -Obusan
Patricia Schirmer
Francesca Cunningham
Rene LaFleur
William Lance
Alysia Maffucci
FDA
BARDAIVY Collaborators
Vanderbilt University
Wesley H. Self
Carlos G. Grijalva
Yuwei Zhu
Cassandra A. Johnson
H. Keipp Talbot
Kelsey N. Womack
Jillian P. Rhoads
Adrienne Baughman
Sydney A. Swan
Todd W. Rice
Jonathan D. Casey
Paul W. Blair
Natasha Halasa
James D. Chappell
Baylor, Scott and White
Manju Gaglani
Shekhar Ghamande
Tresa McNeal
Cristie Columbus
Robert L. Gottlieb
Catherine Raver
Baystate Medical Center
Jay S. Steingrub
Beth Israel Medical Center
Nathan I. Shapiro
Cleveland Clinic
Abhijit Duggal
Emory University
Laurence W. Busse
William S. Bender
Hennepin County
Matthew E. Prekker
Anne Frosch
Johns Hopkins University
David N. HagerIVY Collaborators
Intermountain Health
Ithan D. Peltan
Samuel M. Brown
Emory University
Laurence W. Busse
William S. Bender
Hennepin County
Matthew E. Prekker
Anne Frosch
Intermountain Health
Ithan D. Peltan
Samuel M. Brown
Montefiore Medical Center
Michelle N. Gong
Amira Mohamed
Ohio State Medical Center
Matthew C. Exline
Oregon Health and Sciences
University
Catherine L. Hough
Akram Khan
Stanford University
Jennifer G. Wilson
University of Arizona
Jarrod Mosier
Beth Salvagio  Campbell
UCLA
Nida Qadir
Steven Y. Chang
University of Colorado
Adit A. Ginde
University of Iowa
Nicholas M. Mohr
Anne Zepeski
University of Miami
Christopher MallowIVY Collaborators
University of Michigan
Adam S. Lauring
Emily T. Martin
Aleda M. Leis
University of Utah
Estelle S. Harris
University of Washington
Nicholas J. Johnson
Vasisht  Srinivasan
Wake Forest University
Kevin W. Gibbs
Washington University
Jennie H. Kwon
Bijal Parikh
Henry Ford Health
Ivana A. Vaughn
Mayur Ramesh
Yale University
Basmah SafdarVISION Collaborators
University of Colorado
Toan C. Ong
Suchitra Rao
David Mayer
Michelle Barron
Westat
Sarah Ball
Margaret Dunne
Patrick Mitchell
Sarah E. Reese
Elizabeth A.K. Rowley
Janet Watts
Zack Weber
Additional slides
Cumulative RSV vaccine coverage among adults aged
≥60 years, September 30, 2023 – May 11, 2024
Data source: National Immunization Survey – Adult COVID Module. Available at: Respiratory Syncytial Virus (RSV) Vaccination Coverage and Intent for Vaccination, Adults 60 Years and Older, United
States | CDC . Accessed on June 13, 2024.By May 11, 2024, an estimated
24% of adults aged ≥60 years
had received RSV vaccination
Most RSV vaccinations were administered in pharmacy
settings
Data source: Dr. Carla Black. Implementation update: older adult RSV vaccination. ACIP Meeting, February 29, 2024. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-
29/04 -RSV-Adults -Black -508.pdf   By May 11, 2024, an estimated
24% of adults aged ≥60 years
had received RSV vaccination

Test-negative Design (TND)
•Advantage of TND compared with traditional
case -control or cohort analyses
-Efficiency in enrolling cases and controls from the
same location with the same clinical syndrome
-Reduces selection bias due to healthcare -seeking
behaviorStandardized clinical syndrome
is used to enroll symptomatic
patients seeking medical care
Laboratory test
Positive
CaseNegative
Control
Chua H, et. al., The Use of Test -negative Controls to Monitor Vaccine Effectiveness: A Systematic Review of Methodology. Epidemiology . 2020;31(1): 43 –64.
Definitions of immunocompromise for each observational
VE analysis
Analysis Immunocompromising conditions
IVY Network Active solid tumor or hematologic malignancy (i.e., newly diagnosed malignancy or treatment for a
malignancy within the previous 6 months), solid organ transplant; bone marrow/hematopoietic stem
cell transplant, HIV infection, congenital immunodeficiency syndrome; use of an immunosuppressive
medication within the previous 30 days.
VISION Defined based on presence of ICD -10 code corresponding to hematologic malignancy, solid
malignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune condition or
immunodeficiency, or HIV in discharge diagnoses.
Veterans Health Administration Receipt of immunosuppressive or cancer medications within 90 days or 1 year of index date,
depending on the medication OR
HIV with most recent CD4 lymphocyte count ≤2 years prior to index date ≤200 cells/mm3 OR
Hematologic malignancy documented ≤2 years prior to index date.
Medicare/ESRD At least 2 encounters with a discharge diagnosis for an immunocompromising condition (Hematologic
malignancy, other intrinsic immune conditions or immunodeficiency, solid malignancy, transplant, or
rheumatologic/inflammatory disorders) within 183 days before the index date.
Definitions of chronic lung disease for each observational
VE analysis
Analysis Chronic lung disease definition
IVY Network Asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, pulmonary
hypertension, home oxygen use (except at night for sleep disorder), tracheostomy, home non -invasive
ventilation (except at night for sleep disorder), home invasive ventilation.
VISION Documentation of ICD -10 code corresponding to one or more of the following conditions among
discharge diagnosis codes for encounter:  asthma, chronic obstructive pulmonary disease, cystic
fibrosis, other chronic lung disease.
Veterans Health Administration Any documentation of the following ICD -10 codes within 2 years prior to the index date: B44.81, I27.x,
I28.x, J40.x, J41.x, J42.x, J43.x, J44.0, J44.1, J44.9, J45.x, J47.x, J63.1, J68.4, J70.1, J81.1, J82.8x, J84.03,
J84.10, J84.112, J84.17x, J84.89, J98.2 -.3, M05.10x -.19, M30.1, P25.0, P25.8, Q32.2 -.2, Q33.x, T79.7XXx,
T81.82Xx
Medicare/ESRD Claim listing ICD -10 code corresponding to one or more of the following conditions within 365 days
from the index date:  asthma, chronic obstructive pulmonary disease, other chronic lung disease.
Definitions of cardiovascular disease for each
observational VE analysis
Analysis Cardiovascular disease definition
IVY Network Heart failure, peripheral vascular disease that limits mobility, prior myocardial infarction, cardiac
arrhythmias (including atrial fibrillation, and ventricular arrhythmias), valvular heart disease,
hypertension, untreated thoracic or abdominal aneurysm.
VISION Documentation of ICD -10 code corresponding to one or more of the following conditions among
discharge diagnosis codes for encounter: heart failure, ischemic heart disease, hypertension, other
heart disease, pulmonary embolism, heart valve disorders, atrial fibrillation and flutter, congenital heart
disease.
Veterans Health Administration Any documentation of the following ICD -10 codes within 2 years prior to the index date: ICD10 codes:
E08.52, E09.52, E10.5x, E11.5x, E13.5x, G45.9, I20.0 -.1, I20.8 -.9, I20.0x, I21.0x -.9x, I21.Ax, I22.x, I24.x, I25.x,
I50.x, I63.x, I65.x, I70.x, I73.9, I74.0x, I74.10, I74.19, I74.3 -.8, I75.02x, I77.1, I96.x, L97.101 -.104, L97.109,
L97.111 -.114, L97.119, L97.121 -.124, L97.129, L97.201 -.204, L97.209, L97.211 -.214, L97.219, L97.221 -.224,
L97.229, L97.301 -.304, L97.309, L97.311 -.314, L97.319, L97.321 -.324, L97.329, L97.401 -.404, L97.409,
L97.411 -.414, L97.419, L97.421 -.424, L97.429, L97.501 -.504, L97.509, L97.511 -.514, L97.519, L97.521 -.524,
L97.529, L97.801 -.804, L97.809, L97.811 -.814, L97.819, L97.821 -.824, L97.829, L97.901 -.904, L97.909,
L97.911 -.914, L97.919, L97.921 -.924, L97.929, Z95.1, Z95.5, Z98.61
Medicare/ESRD Claim listing ICD -10 code corresponding to one or more of the following conditions within 365 days
from the index date:  heart failure, ischemic heart disease, hypertension, other cardiovascular disease.
Case definitions of lower respiratory tract illness or
disease in RSV vaccine trials1,2
1Papi A, et al; AReSVi -006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med . 2023;388(7):595 -608
2Walsh EE, et al; RENOIR Clinical Trial Group. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med . 2023;388(16):1465 -1477Pfizer ( Abrysvo )2
▪ RSV LRTI with ≥2 lower respiratory
signs/symptoms (co -primary outcome)
▪ RSV LRTI with ≥3 lower respiratory
signs/symptoms (co -primary outcome)
▪ Lower respiratory signs/symptoms :
•Sputum, cough, shortness of
breath, wheezing, tachypneaGSK ( Arexvy )1
▪ RSV LRTD (primary outcome)
– ≥2 lower respiratory symptoms  or signs ,
including ≥1 sign, OR
– ≥3 lower respiratory symptoms
▪ Lower respiratory symptoms :
– Sputum, cough, dyspnea
▪ Lower respiratory signs :
– Wheezing, crackles/rhonchi, tachypnea,
hypoxemia, oxygen  supplementation
Original slides
•The following slides contain errata. They are being shared here for a
record of what was presented at the June 26, 2024, ACIP meeting.
•Corrected slides are available in the main presentation.
•Corrected slides with changes highlighted are included in the
following slides.
44
Comparison of demographic characteristics among
IVY , VISION, VHA, and Medicare/ESRD studies
IVY ,
no. (col %)VISION ,
no. (col %)VHA ,
no. (col %)Medicare/ESRD ,
no. (col %)
Characteristic Total no.
of
patientsTotal no.
of
patientsTotal no.
of
patientsTotal no.
of
patients
All patients 2,978 36,706 293,704§69,279
Median age, years (IQR) 72 (66 –80) 76 (69 –84) 76 (72 –80) 74 (70-80)
Age group, years
 60–74 1756 (59) 16,055 (44) 125,124 (43) 34,614 (50)‡
 ≥75 1222 (41) 20,651 (56) 168,580 (57) 34,665 (50)
Race and ethnicity
 White, non -Hispanic 1867 (63) 27,057 (74) 225,713 (77) 42,157 (61)
 Black, non -Hispanic 582 (20) 3,160 (9) 30,359 (10) 14,767 (21)
 Hispanic or Latino, any race 335 (11) 2,789 (8) 11,302 (4) 3,983 (6)
 Other race, non -Hispanic*101 (3) 3,395 (9) 5,971 (2) 3,604 (5)
 Unknown†93 (3) 305 (1) 20,358 (7) -
* For VISION, “Other race, non -Hispanic” includes persons reporting non -Hispanic ethnicity and any of the following for race: Am erican Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander,
other races not listed, and multiple races; because of small numbers, these categories were combined. For IVY, “Other race, n on-Hispanic” includes Asian, American Indian or Alaska Native, and Native Hawaiian
or other Pacific Islander; because of small numbers, these categories were combined.
† For VISION, “Unknown” includes persons with missing race and ethnicity in their electronic health records. For IVY, “Unknow n” includes patients who self -reported their race and ethnicity as “Other” and those
for whom race and ethnicity were unknown. For VHA “Unknown” includes missing, unknown, or declined race or ethnicity.
§146,852 vaccinated persons were matched to 582,936 unvaccinated participants who were equally weighted to correspond to 146,8 52 matched unvaccinated participants.
‡Evaluation of Medicare fee -for-service claims data was restricted to adults aged 65 years and older.This slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 5 ; to see the corrected slide with changes highlighted, see slide 46.
Comparison of demographic characteristics among
IVY , VISION, VHA, and Medicare/ESRD studies
IVY ,
no. (col %)VISION ,
no. (col %)VHA ,
no. (col %)Medicare/ESRD ,
no. (col %)
Characteristic Total no.
of
patientsTotal no.
of
patientsTotal no.
of
patientsTotal no.
of
patients
All patients 2,978 36,706 293,704§69,279
Median age, years (IQR) 72 (66 –80) 76 (69 –84) 76 (72 –80) 75 (70-80)
Age group, years
60–74 1756 (59) 16,055 (44) 125,124 (43) 34,614 (50)‡
≥75 1222 (41) 20,651 (56) 168,580 (57) 34,665 (50)
Race and ethnicity
White, non -Hispanic 1867 (63) 27,057 (74) 225,713 (77) 42,157 (61)
Black, non -Hispanic  582 (20) 3,160 (9) 30,359 (10) 14,767 (21)
Hispanic or Latino, any race 335 (11) 2,789 (8) 11,302 (4) 3,983 (6)
Other race, non -Hispanic*101 (3) 3,395 (9) 5,971 (2) 8,372 (12)
Unknown†93 (3) 305 (1) 20,358 (7) -
* For VISION, “Other race, non -Hispanic” includes persons reporting non -Hispanic ethnicity and any of the following for race: Am erican Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander,
other races not listed, and multiple races; because of small numbers, these categories were combined. For IVY, “Other race, n on-Hispanic” includes Asian, American Indian or Alaska Native, and Native Hawaiian
or other Pacific Islander; because of small numbers, these categories were combined. For Medicare/ESRD, "Other race, non -Hispanic" includes Asian/Pacific Islander, non -Hispanic, Other, non -Hispanic, and
Unknown.
† For VISION, “Unknown” includes persons with missing race and ethnicity in their electronic health records. For IVY, “Unknow n” includes patients who self -reported their race and ethnicity as “Other” and those
for whom race and ethnicity were unknown. For VHA “Unknown” includes missing, unknown, or declined race or ethnicity.
§146,852 vaccinated persons were matched to 582,936 unvaccinated participants who were equally weighted to correspond to 146,8 52 matched unvaccinated participants.
‡Evaluation of Medicare fee -for-service claims data was restricted to adults aged 65 years and older.This slide has been corrected (highlighted). To see the slide as originally presented, please see slide 45; to see a correcte d, unhighlighted version, see slide 5.
Comparison of clinical characteristics among IVY ,
VISION, VHA, and Medicare/ESRD studies
IVY ,
no. (col %)VISION ,
no. (col %)VHA ,
no. (col %)Medicare/ESRD ,
no. (col %)
Characteristic Total no.
of
patientsTotal no.
of
patientsTotal no.
of
patientsTotal no.
of
patients
All patients 2,978 36,706 293,704 69,279
No. of chronic medical condition categories
0 71 (2) 2,111 (6) 17,554 (6) 0 (0)
1 416 (14) 3,845 (10) 58,757 (20) 312 <1)
2 783 (26) 15,420 (42) 83,992 (29) 1,497 (2)
3 863 (29) 15,330 (42) 73,296 (25) 9,242 (13)
≥4 845 (28) 2,111 (6) 60,106 (21) 58,228 (84)
Immunocompromised*720 (24) 8,435 (23) 32,996 (11) 17,499 (25)
Chronic lung disease†1423 (48) 17,541 (48) 88,648 (30) 38,529 (56)
Cardiovascular disease§2501 (84) 28,822 (79) 122,015 (42) 66,987 (97)
RSV vaccinated 265 (9) 3,275 (9) 146,852 (50)¶6,73 4 (10)
 Received GSK (Arexvy) 137 (61)** 2,409 (74) 43,875 (30) 4,562 68)
 Received Pfizer (Abrysvo) 89 (39) ** 865 (36) 101,623 (69) 2,172 (32)
* Slide 41 provides definitions of immunocompromise from each network
† Slide 42 provides definitions of chronic lung disease from each network
§ Slide 43 provides definitions of cardiovascular disease from each network
¶ Each RSV -vaccinated patient was matched to up to 4 unvaccinated, equally weighted patients, resulting in 50% of matched persons having an RSV vaccination. Among match -eligible patients, 4.5% received RSV vaccination.
** Of 265 RSV vaccinated patients in IVY, 226 (85%) had known product type, which is used as the denominator for these percentag es.This slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 6 ; to see the corrected slide with changes highlighted, see slide 48.
Comparison of clinical characteristics among IVY ,
VISION, VHA, and Medicare/ESRD studies
IVY ,
no. (col %)VISION ,
no. (col %)VHA ,
no. (col %)Medicare/ESRD ,
no. (col %)
Characteristic Total no.
of
patientsTotal no.
of
patientsTotal no.
of
patientsTotal no.
of
patients
All patients 2,978 36,706 293,704 69,279
No. of chronic medical condition categories
0 71 (2) 2,111 (6) 17,554 (6) 0 (0)
1 416 (14) 3,845 (10) 58,757 (20) 312 (<1)
2 783 (26) 15,420 (42) 83,992 (29) 1,497 (2)
3 863 (29) 15,330 (42) 73,296 (25) 9,242 (13)
≥4 845 (28) 2,111 (6) 60,106 (21) 58,228 (84)
Immunocompromised*720 (24) 8,435 (23) 32,996 (11) 17,499 (25)
Chronic lung disease†1423 (48) 17,541 (48) 88,648 (30) 38,529 (56)
Cardiovascular disease§2501 (84) 28,822 (79) 122,015 (42) 66,987 (97)
RSV vaccinated 265 (9) 3,275 (9) 146,852 (50)¶6,73 1 (10)
Received GSK (Arexvy) 137 (61)** 2,409 (74) 43,875 (30) 4,559 (68)
Received Pfizer (Abrysvo) 89 (39) ** 865 (36) 101,623 (69) 2,172 (32)
* Slide 41 provides definitions of immunocompromise from each network
† Slide 42 provides definitions of chronic lung disease from each network
§ Slide 43 provides definitions of cardiovascular disease from each network
¶ Each RSV -vaccinated patient was matched to up to 4 unvaccinated, equally weighted patients, resulting in 50% of matched persons having an RSV vaccination. Among match -eligible patients, 4.5% received RSV vaccination.
** Of 265 RSV vaccinated patients in IVY, 226 (85%) had known product type, which is used as the denominator for these percentag es.This slide has been corrected (highlighted). To see the slide as originally presented, please see slide 47; to see a correcte d, unhighlighted version, see slide 6.
*RSV -associated hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revi sion, Clinical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at
least one inpatient facility claim in the primary position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with pneumonia or acute respiratory failure outcome code.
†Defined as having at least one dialysis encounter (excluding acute kidney injury) in the 90 days preceding the index date. Pe rsons with end stage renal disease receiving dialysis are eligible for Medicare benefits, regardless of age.
§At least 2 encounters with a discharge diagnosis for an immunocompromising condition (hematologic malignancy, solid tumor mal ignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune conditions or
immunodeficiency) within 183 days before the index date.
¶A single beneficiary can contribute follow -up time in multiple categories.
**Adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and Updated (2023 -2024 Formula) COVID -19 vaccination status. VE was calculated as (1 − adjusted hazard ratio) x 100%.
††Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose
administration.
§§ Centers for Medicare & Medicaid Services (CMS) cell suppression policy limits the minimum cell size.
¶¶Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point
estimate shown, and estimates should therefore be interpreted with caution.Medicare/ESRD: VE against RSV -associated hospitalization* among adults aged ≥65
years with ESRD†, by immunocompromise status§,  October 2023 –February 2024
Immunocompromise status |
vaccination status# of
Beneficiaries# of
OutcomesMedian
Follow -up
Time (Days) ¶Vaccine Effectiveness,
% (95% CI)**
Without  Additional Immunocompromise
Unvaccinated (Ref) 47,17 6 275 146 Ref
Vaccinated†† 4,60 4 <11§§ 91 78 (45–91)
With  Additional Immunocompromise
Unvaccinated (Ref) 15,3 69 136 146 Ref
Vaccinated 2,130 <11§§ 90 80 (31–94) ¶¶
0 50 100
Vaccine Effectiveness, % (95% CI)RSV vaccination provided protection
against RSV -associated hospitalization
among adults with ESRD on dialysisThis slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 3 0; to see the corrected slide with changes highlighted, see slide 50.
*RSV -associated hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revi sion, Clinical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at
least one inpatient facility claim in the primary position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with pneumonia or acute respiratory failure outcome code.
†Defined as having at least one dialysis encounter (excluding acute kidney injury) in the 90 days preceding the index date. Pe rsons with end stage renal disease receiving dialysis are eligible for Medicare benefits, regardless of age.
§At least 2 encounters with a discharge diagnosis for an immunocompromising condition (hematologic malignancy, solid tumor mal ignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune conditions or
immunodeficiency) within 183 days before the index date.
¶A single beneficiary can contribute follow -up time in multiple categories.
**Adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and Updated (2023 -2024 Formula) COVID -19 vaccination status. VE was calculated as (1 − adjusted hazard ratio) x 100%.
††Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose
administration.
§§ Centers for Medicare & Medicaid Services (CMS) cell suppression policy limits the minimum cell size.
¶¶Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point
estimate shown, and estimates should therefore be interpreted with caution.Medicare/ESRD: VE against RSV -associated hospitalization* among adults aged ≥65
years with ESRD†, by immunocompromise status§,  October 2023 –February 2024
Immunocompromise status |
vaccination status# of
Beneficiaries# of
OutcomesMedian
Follow -up
Time (Days) ¶Vaccine Effectiveness,
% (95% CI)**
Without  Additional Immunocompromise
Unvaccinated (Ref) 47,17 7 342 146 Ref
Vaccinated†† 4,60 3 <11§§ 91 72 (41-87)
With  Additional Immunocompromise
Unvaccinated (Ref) 15,3 71 161 146 Ref
Vaccinated 2,128 <11§§ 90 83 (45-95) ¶¶
0 50 100
Vaccine Effectiveness, % (95% CI)RSV vaccination provided protection
against RSV -associated hospitalization
among adults with ESRD on dialysisThis slide has been corrected (highlighted). To see the slide as originally presented, please see slide 49; to see a correcte d, unhighlighted version, see slide 30.
Outcome Analysis Vaccine efficacy /effectiveness,  % (95% CI)
Symptomatic,
RSV -associated
lower
respiratory tract
disease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†83 (58 –94)
Pfizer trial (≥2 sx LRTI, co -primary endpoint) * 67 (29 –86)
Pfizer trial (≥3 sx LRTI, co -primary endpoint) * 86 (32 –99)
RSV -associated
hospitalizationIVY Network, adults ≥60 years§75 (50 –87)
VISION, adults ≥60 years, immunocompetent 80 (71 –85)
VHA, adults ≥60 years§82 (69 –89)
Medicare ESRD, otherwise immunocompetent, ≥65y 78 (45–91)
VISION, immunocompromised 73 (48 –85)
Medicare ESRD, additional immunocompromise, ≥65y 80 (31–94)Observational VE studies show RSV vaccines protect against severe RSV
disease, similar to results from trials, although endpoints differ
0 20 40 60 80 100
Vaccine effectiveness, % (95% CI)
† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 4 3 for detailed definitions.
* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 4 3 for detailed definitions.
§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; y = yearsThis slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 3 2; to see the corrected slide with changes highlighted, see slide 52.
Outcome Analysis Vaccine efficacy /effectiveness,  % (95% CI)
Symptomatic,
RSV -associated
lower
respiratory tract
disease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†83 (58 –94)
Pfizer trial (≥2 sx LRTI, co -primary endpoint) * 67 (29 –86)
Pfizer trial (≥3 sx LRTI, co -primary endpoint) * 86 (32 –99)
RSV -associated
hospitalizationIVY Network, adults ≥60 years§75 (50 –87)
VISION, adults ≥60 years, immunocompetent 80 (71 –85)
VHA, adults ≥60 years§82 (69 –89)
Medicare ESRD, otherwise immunocompetent, ≥65y 72 (41-87)
VISION, immunocompromised 73 (48 –85)
Medicare ESRD, additional immunocompromise, ≥65y 83 (45-95)Observational VE studies show RSV vaccines protect against severe RSV
disease, similar to results from trials, although endpoints differ
0 20 40 60 80 100
Vaccine effectiveness, % (95% CI)
† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 4 3 for detailed definitions.
* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 4 3 for detailed definitions.
§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; y = yearsThis slide has been corrected (highlighted). To see the slide as originally presented, please see slide 51; to see a correcte d, unhighlighted version, see slide 32.

Summary: Effectiveness of adult respiratory syncytial virus (RSV)   vaccines, 2023 –2024 Diya Surie, MD Coronavirus and Other Respiratory Viruses Division Centers for Disease Control and Prevention June 26, 2024National Center for Immunization and Respiratory Diseases This presentation has been  corrected. See slides 5, 6, 30,  and 32 for corrected slides. The  original slides are included at  the end of the presentation. •Purpose of randomized vaccine trials is to answer the question:Goal of…


08 RSV Adult Hutton 508

Economic Analysis of RSV Vaccination
in Adults 50 years and Older
David W. Hutton, PhD, MS
Associate Professor, Health Management and Policy, School of Public Health
Associate Professor of Global Public Health, School of Public Health
Associate Professor, Industrial and Operations Engineering, College of Engineering
University of Michigan
1
Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Christina Nyamuswa , MSCDC
•Michael Melgar, MD
•Amadea Britton, MD
•Lauren Roper, MPH
•Mila Prill, MSPH
•Jamison Pike, PhD
•Ismael Ortega -Sanchez, PhD
•Andrew Leidner, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Rebecca Woodruff, PhD
•Huong Pham, MPH
•Bryan Stierman , MD
2
Conflicts of interest  statements
•No known conflict of interests.
3
Updates from last presentation before ACIP in
June 2023*
•Risk-Based Analysis
•Groups based on chronic medical conditions (CMCs) and age
•Added Moderna Vaccine
•Other New Inputs
•RSV Epidemiology
•Hospitalization incidence by chronic medical conditions
•Outpatient incidence by chronic medical condition
•RSV-mortality inclusive of deaths in and out of hospital
•Real -world observational vaccine effectiveness of RSV protein subunit vaccination
(Pfizer/GSK)
•Duration of protection derived from clinical trial efficacy waning over time using all available
follow up time
•Vaccine adverse events after protein subunit RSV vaccination
•Real world evidence on local and systemic vaccine reactions (V -safe)
•Risk of Guillain -Barre syndrome (GBS) observed after RSV vaccination in administrative claims
data through FDA/CMS partnership
4* DW Hutton, “Economic Analysis of RSV Vaccination in Older Adults” June 21, 2023 (cdc.gov)
Methods
5
Methods: Study question
•Determine the cost -effectiveness of RSV vaccination by:
•Comparing vaccination to no vaccination using the incremental cost -
effectiveness ratio
•Scenario analyses.
•Perspective: Societal
6
Methods: Intervention(s)
•Target population: US adults aged ≥50 years, stratified by age, chronic
medical conditions
•Adults aged ≥75 years
•Adults aged 60 -74 years with at least one chronic medical condition*
•Adults aged 50 -59 years with at least one chronic medical condition*
•Interventions: RSV vaccination
•Protein subunit RSV vaccination (Pfizer’s ABRYSVO, GSK’s AREXVY)
•Moderna RSV vaccination (Moderna’s mRESVIA )
•Each compared to no vaccination
7*At least one of: chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic kidney disease,
diabetes mellitus, severe obesity (BMI ≥40)
Combining Pfizer and GSK in base case
•ACIP has previously seen that product -specific cost effectiveness for
the two currently licensed protein subunit RSV vaccines is similar
•Policy question does not distinguish between the two products
•Combining products allows simplification of results and enables us to
focus on the policy questions
•Product -specific results will still be shown in scenario analyses
•Benefit/risk analyses evaluating GBS risk will be shown at the end and
continue to be product -specific, understanding whether there is
meaningful difference between products in terms of benefit/risk
balance
8
Methods: Decision Tree Model
9No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
Dead
RSV Infection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventInfection RSV Infection
Guillain Barre Syndrome
Annual RSV Incidence
•Hospitalization s
•RSV-NET estimated annual hospitalizations per 100,000 population  (adjusted for under -
detection, including a 1.5x multiplier to account for RSV test sensitivity)
•Source, age stratification only: Havers et al. manuscript draft, 2016 -2020
•Source, stratification by age AND presence/absence of chronic medical conditions: Update to Woodruff
et al. analysis presented to ACIP in February 2024, 2017 -20181
•Emergency Department visits:
•From McLaughlin et al. meta -analysis2 (main results incorporating a 1.5x multiplier to account
for RSV laboratory test sensitivity).
•No differences by presence or absence of chronic medical conditions*
•Outpatient:
•The base values ( all-comers ) are from the McLaughlin et al. meta -analysis.2
•Values for adults with chronic cardiopulmonary conditions (e.g., COPD) are drawn from
Belongia  et al.3 and multiplied by 1.5x for test sensitivity to align with RSV -NET and
McLaughlin et al. methods.
•Non -cardiopulmonary conditions (e.g., diabetes) utilize the base values (same as for all -
comers)
*Values were assumed to be the same for adults with and without chronic medical conditions. This is a conservative assumption mad e in the absence of reliable risk -stratified data on the
incidence of emergency department visits.
1. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf
2. Pfizer -sponsored: McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infect Dis. 2022 J un 17;9(7):ofac300. doi:
10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.
3. Novavax sponsored: Belongia  EA, et al. Clinical features, severity, and incidence of RSV illness during 12 consecutive seasons in a community cohort of a dults ≥60 years old. In Open forum infectious
diseases 2018 Dec (Vol. 5, No. 12, p. ofy316). US: Oxford University Press10
Annual RSV incidence
•At least one chronic medical condition (source RSV -NET):
•Chronic obstructive pulmonary disease (COPD), OR
•Asthma, OR
•Coronary artery disease (CAD), OR
•Diabetes mellitus, OR
•Chronic kidney disease (CKD), OR
•Severe obesity (body mass index [BMI] ≥40 kg/m2)
•Additional chronic medical conditions evaluated in scenario analyses:
•Heart failure1
•Immune compromised
•Lung transplant2
•Hematopoietic cell transplant, allogeneic3,4
•Hematopoietic cell transplant, autologous3,4
1. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022
Mar 9;17(3):e0264890. doi: 10.1371/journal.pone.0264890
2. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin
Microbiol  Infect. 2021 Jun;27(6):897 -903. doi: 10.1016/j.cmi.2020.07.050.
3. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in adult
recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct;11(10) :781-96. doi: 10.1016/j.bbmt.2005.07.007
4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244.
doi: 10.1093/ infdis /jix390These conditions  are considered separately
because RSV epidemiologic parameters were
derived from different published sources and
cannot be combined with RSV -NET hospitalization
rate estimates under “at least one” condition.
11
Annual RSV incidence
•At least one chronic medical condition (source RSV -NET):
•Chronic obstructive pulmonary disease (COPD), OR
•Asthma, OR
•Coronary artery disease (CAD), OR
•Diabetes mellitus, OR
•Chronic kidney disease (CKD), OR
•Severe obesity (body mass index [BMI] ≥40 kg/m2)
•Additional chronic medical conditions evaluated in scenario analyses:
•Heart failure1
•Immune compromised
•Lung transplant2
•Hematopoietic cell transplant, allogeneic3,4
•Hematopoietic cell transplant, autologous3,4
121. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022 Mar
9;17(3):e0264890. doi: 10.1371/journal.pone.0264890
2. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin
Microbiol  Infect. 2021 Jun;27(6):897 -903. doi: 10.1016/j.cmi.2020.07.050.
3. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in adult
recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct;11(10) :781-96. doi: 10.1016/j.bbmt.2005.07.007
4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244.
doi: 10.1093/ infdis /jix390Assumed that vaccine effectiveness was
reduced by half in immune compromised
populations, compared with all others
Vaccine effectiveness (VE) of a single dose over time:
protein subunit RSV vaccine (combined Pfizer/GSK)
13Linear decay to 0%
by 24 months74%
33%
17%78%
58%
33%80%
60%
34%
0%10%20%30%40%50%60%70%80%90%100%
0 6 12 18 24 30 36Efficacy
Months since vaccination
Outpatient ED Hospitalization
VE against hospitalization and emergency department visits during months 0 -6 post -vaccination was assumed to be equal to results of  a meta -analysis of observational VE
estimates from CDC and Veterans Health Administration analyses from the first RSV season of vaccine availability. Proportiona l waning was applied from clinical trial vaccine
efficacy over time against RSV lower respiratory tract illness with ≥3 signs/symptoms (Pfizer ABRYSVO) and RSV lower respirat ory tract disease (GSK AREXVY) (data provided by
manufacturers). VE against outpatient illness was assumed to be the mean across the two products of trial efficacy against RS V acute respiratory illness.
0%10%20%30%40%50%60%70%80%90%100%
0 6 12 18 24 30 36Efficacy
Months since vaccination
Outpatient ED HospitalizationVaccine effectiveness (VE) of a single dose over time:
Moderna RSV vaccine ( mRESVIA )
1475%
54%
Linear decay to 0%
by 24 months54%
VE against hospitalization during months 0 -9 post -vaccination was assumed to be equal to clinical trial vaccine efficacy against  medically attended RSV lower respiratory tract
disease with ≥3 signs/symptoms. VE against emergency department visits and outpatient illness during months 0 -9 was assumed to b e equal to clinical vaccine efficacy against
medically attended RSV acute respiratory illness. VE was assumed to decline to zero by month 24 post -vaccination.
•Pfizer and GSK systemic and injection site adverse event rates updated based on real -world V -
safe data:
•Pfizer: 6% experienced severe  injection site reaction or systemic reaction
•GSK: 10% experienced severe  injection site reaction or systemic reaction
•Pfizer and GSK Guillain Barre syndrome (GBS) risk updated based on FDA active surveillance
through partnership with CMS, Medicare beneficiaries ages ≥65 years1, vaccinations during
May –October 8, 2023:
•Pfizer: 16 GBS cases (95% CI 3 –29) per 1 million doses administered2
•GSK: 3 GBS cases (95% CI 0 –10) per 1 million doses administered2,3
•Moderna data based on trial
•Moderna: 7% experienced severe  injection site reaction or systemic reaction
•Assumed no vaccine -attributable GBS risk
•All Vaccines: rare, unnamed serious adverse event of 1 per million doses administered
15Methods: Adverse Events
Abbreviations: CI = confidence interval, CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administrat ion, GBS = Guillain -Barre
syndrome
1.Must have been enrolled in Medicare Parts A, B and D. Must not have had a diagnostic code for GBS in the 365 days preceding v accination.
2.These estimates reflect vaccine -attributable risk of GBS in excess of background rate of GBS among adults ages ≥65 years vaccina ted with the same product.
This analysis extrapolated from the study population and assumed the same risk applied to adults ages 50 –64 years.
3.Attributable risk for GSK’s AREXVY was estimated to be 3 GBS cases (95% CI: -3, 10) per 1 million doses. For mathematical modeling , lower end of the 95% CI
was truncated at 0 to evaluate potential risk  of GBS. Potential protective effects were not evaluated.
Methods: Base RSV Medical Costs
Variable Value Range Source
Disease -specific hospitalization costs (per hospitalization)
age 50 to <60 years $20,330 9,511 – 39,544
Ackerson 2020*age 60 to <65 years $21,417 9,288 – 45,454
age 65 to <75 years $21,417 10,491 – 43,619
age ≥75 years $22,425 10,491 – 43,619
Disease -specific ED costs (per ED visit)
age 60 to <65 years $1,210 -
2016 Marketscan* age 65 to <75 years $1,210 -
age ≥75 years $1,210 -
Disease -specific outpatient costs (per outpatient visit)
age 60 to <65 years $117.58 65.88 -145.38MarketScan  and Medicare FFS,
2020 -2021age 65 to <75 years $100.86 50.48 -120.08
age ≥75 years $100.86 50.48 -120.08
16
*Updated to 2023 using GDP Deflator
Methods: Hospitalization cost multiplier based on chronic
medical conditions
17Condition Condition -specific multiplier, based on median length of stay (RSV -NET)
At least one condition* 1.06
With COPD 1.22
With Asthma 1.0
With CAD 1.13
With Diabetes 1.11
With severe obesity, BMI ≥40 1.0
With CKD 1.26
None of these conditions** 0.84
With Heart Failure 1.28
Immune Compromise 1.06
*Have at  least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, severe obesity (BMI ≥40), chronic kidney
disease; may also have other conditions such as heart failure or immune compromise
** None of the conditions in the at least one definition, but may have other conditions such as heart failure or immune compr omise
Methods: Vaccination -Related Costs
Variable Value Range Source
Vaccine, per dose
Pfizer $295 List price
GSK $280 List price
Moderna $290 Manufacturer Assumption
Vaccine administration $16.96 -HCPCS 90460 (Physician Fee Schedule
2022)
18
Methods: Additional Inputs
•Also included
•RSV illness QALYs lost
•RSV illness productivity costs
•Vaccination healthcare and productivity costs
•Vaccination adverse events
•Medical costs
•Productivity costs
•These assumptions remain unchanged from October 2023
19* DW Hutton, “Economic Analysis of RSV Vaccination in Older Adults” June 21, 2023 (cdc.gov)
Methods: Scenarios
•Manufacturer -specific (Pfizer and GSK -specific models; Moderna is
considered separately in the base case, so no scenario needed)
•Assuming longer duration of protection (efficacy declines to 0 at 36
rather than at 24 months)
•Among persons without chronic medical conditions
•Condition -specific (e.g., among persons with heart failure)
20
Base case results
21
Base case Incremental Cost -Effectiveness
Ratios ($/QALY)
Protein subunit RSV
vaccines
(combined Pfizer + GSK)Moderna RSV vaccine
All adults 75+ $              51,447  $              66,287
Adults 60 -74 with at
least 1 condition1 $              60,933  $              80,953
Adults 50 -59 with at
least 1 condition1,2 $           154,501
1. At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic
kidney disease, severe obesity (BMI ≥40)
2. Only a single vaccine (GSK AREXVY) is licensed in adults 50 -59. So, this uses GSK -specific input parameters for this
age group.
BMI: body mass index, QALY: Quality -Adjusted Life -Year 22
Incremental Cost -Effectiveness
QALY: Quality -Adjusted Life -Year
23At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity
(BMI ≥40)Protein subunit vaccine All
adults ≥75
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000
 -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)
Incremental QALYs Saved (Thousands)
Incremental Cost -Effectiveness
QALY: Quality -Adjusted Life -Year
24At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity
(BMI ≥40)Protein subunit vaccine All
adults ≥75 $51,447/QALY
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000
 -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)
Incremental QALYs Saved (Thousands)
Incremental Cost -Effectiveness
QALY: Quality -Adjusted Life -Year
25At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity
(BMI ≥40)Protein subunit vaccine All
adults ≥75Protein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 condition
$51,447/QALY$60,933/QALY
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000
 -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)
Incremental QALYs Saved (Thousands)
Incremental Cost -Effectiveness
QALY: Quality -Adjusted Life -Year
26At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity
(BMI ≥40)Protein subunit vaccine All
adults ≥75Protein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 conditionProtein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 condition AND 50 -59
with at least 1 condition
$51,447/QALY$60,933/QALY$154,501/QALY
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000
 -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)
Incremental QALYs Saved (Thousands)
Incremental Cost -Effectiveness
QALY: Quality -Adjusted Life -Year
27At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity
(BMI ≥40)Protein subunit vaccine All
adults ≥75Protein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 conditionProtein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 condition AND 50 -59
with at least 1 condition
Moderna vaccine All adults ≥75
$51,447/QALY$60,933/QALY$154,501/QALY
$66,287/QALY
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000
 -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)
Incremental QALYs Saved (Thousands)
Incremental Cost -Effectiveness
QALY: Quality -Adjusted Life -Year
28At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity
(BMI ≥40)Protein subunit vaccine All
adults ≥75Protein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 conditionProtein subunit vaccine All
adults ≥75 AND 60 -74 with at
least 1 condition AND 50 -59
with at least 1 condition
Moderna vaccine All adults ≥75Moderna vaccine All adults ≥75
AND 60 -74 with at least 1
condition
$51,447/QALY$60,933/QALY$154,501/QALY
$66,287/QALY$80,953/QALY
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000
 -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)
Incremental QALYs Saved (Thousands)
Scenario analyses
29
Protein subunit RSV vaccination: product -
specific
GSK AREXVY Pfizer ABRYSVO
All adults 75+ $        47,050  $        58,739
Adults 60 -74 with at
least 1 condition$        55,006  $        70,624
30At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus,
chronic kidney disease, severe obesity (BMI ≥40)
Time Horizon Comparison
Base case  (24 months of efficacy )
Protein subunit RSV
vaccines
(combined Pfizer +
GSK)Moderna RSV
vaccineProtein subunit RSV
vaccines
(combined
Pfizer+GSK )Moderna RSV
vaccine
All adults 75+ $              51,447  $              66,287  $              39,833  $              42,495
Adults 60 -74
with at least 1
condition$              60,933  $              80,953  $              45,445  $              49,198
Adults 50 -59
with at least 1
condition*$           154,501  $           112,949  Scenario  (36 months of efficacy )
*Only a single manufacturer (GSK) has applied for FDA licensure in adults 50 -59. So, this scenario uses GSK -specific inputs.
31At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease,
severe obesity (BMI ≥40)
Cost -Effectiveness by age and conditions
* At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, severe obesity (BMI ≥40)
** None of the above conditions. Persons may have other chronic medical conditions (e.g., heart failure, non -severe obesity, imm une compromise).32$14,636 $60,933 $154,501
$22,905 $80,953 $168,075 $505,385
$202,918 $608,761
 $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000
Adults ≥75  Adults 60-74 Adults 50-59 Adults ≥75  Adults 60-74
Protein subunit vaccine GSK Moderna vaccineICER ($ per QALY gained)
At least one condition* None of these conditions**
Scenarios: Cost -effectiveness of vaccinating adults with
specific chronic conditions
Protein subunit RSV
vaccines
(combined Pfizer+GSK )Moderna RSV vaccine
Adults 60 -74 with specific
conditions : heart failure,
immune compromise,
COPD, asthma, CAD,
diabetes, severe obesity,
chronic kidney disease10 Scenarios 10 Scenarios
Adults 50 -59 with specific
conditions : as above10 Scenarios
(GSK -specific)*
*Only a single vaccine (GSK AREXVY) is licensed in adults 50 -59. So, this uses GSK -specific inputs for this age group.33
$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000
All Adults
At least one condition
 CKD
 COPD
 obesity BMI >40
 Asthma
 CAD
 Diabetes
None of the above…
 Heart Failure
With lung transplant
With allogenic HCT
With autologous HCTIncremental cost effectiveness ratio ($ per QALY gained)
 50-59
 60-74
≥75Scenarios: Adults with specific chronic medical conditions, protein subunit RSV
vaccines (Pfizer/GSK)
*Indicates cost saving
At least one condition refers to: COPD, asthma, coronary artery disease, diabetes
mellitus, chronic kidney disease, severe obesity (BMI ≥40)//$505,385**
*Adults 50 -59 without chronic conditions are not under consideration
Adults 50 -59 without chronic conditions are not under consideration
*
**
†Only a single vaccine (GSK AREXVY) is licensed in adults 50 -59. So, this uses GSK -specific inputs for
this age group.
HCT: Hematopoietic Cell Transplant†
$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000
All Adults
At least one condition
 CKD
 COPD
 obesity BMI >40
 Asthma
 CAD
 Diabetes
None of the above…
 Heart Failure
With lung transplant
With allogenic HCT
With autologous HCTIncremental cost effectiveness ratio ($ per QALY gained)
 60-74
≥75Scenarios: Adults with specific chronic medical conditions, Moderna RSV vaccine
*
*
//$608,761
//$202,918//$217,582
*
*
*
*Indicates cost saving
At least one condition refers to: COPD, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, severe ob esity (BMI ≥40)
HCT: Hematopoietic Cell Transplant
Sensitivity Analysis:
Changing Parameter Assumptions
36
GSK RSV vaccine at least 1 condition age 50 -59
37$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
Incidence of RSV hospitalization
RSV-attributable mortality
RSV QALYs Lost Outpatient Adult
Cost per Hospitalization
VE GSK Hospitalized months 13-23
VE GSK Outpatient months 13-23
Health Utility Age 60-69 years
VE GSK Hospitalized months 0-7
Incidence of outpatient visits for RSV
 GBS Cases per MillionIncremental Cost -Effectiveness Ratio ($/QALY gained)As least one condition Age 50 -59 years GSK
Low Assumption High Assumption
Limitations
•Model Structure
•No dynamic transmission. No impact of the vaccine on transmission and indirect
effects
•We did not include or analyze all potential RSV risk factors.
•Some medical conditions (e.g., interstitial lung disease) are likely associated with
high risk of severe RSV disease, but literature on population -based hospitalization
rates and other outcomes are lacking.
•RSV vaccination may be cost effective for adults with additional conditions that were
not evaluated.
•Uncertain inputs
•Moderna real -world vaccine effectiveness
•Moderna vaccine cost
•RSV burden of disease, especially hospitalization and mortality
•Duration and waning pattern of vaccine protection
38
Conclusions
•If there were a recommendation for RSV vaccination for all adults 75 and older the ICER
would be $51,447 societal cost/QALY saved (Pfizer/GSK) and $66,287/QALY (Moderna) .
•If instead we limited the recommendation only to adults 75 and older with at least one chronic
medical condition the ICER would be $14,636/QALY (Pfizer/GSK) and $22,905 (Moderna)
•If we add in adults 60-74 with at least one chronic medical condition , the ICER would be
$60,933 societal cost/QALY (Pfizer/GSK) and $80,953/QALY (Moderna) .
•Vaccination of adults 60 -74 without  chronic conditions has an ICER of $505,385/QALY (Pfizer/GSK)
and $608,761/QALY (Moderna)
•If we add in adults 50-59 with at least one chronic medical condition the ICER would be
$154,501 societal cost/QALY saved (GSK only).
•By specific condition, $/QALY saved was lowest among adults 50 -59 with heart failure
($14,335/QALY ) and immune compromise ( cost-saving or $14,521/QALY ) and highest among
those with diabetes ($171,661/QALY ).
•Longer duration of protection (36 months rather than 24 months) or higher baseline RSV
disease burden made all policy options more cost effective.
39
Thank You
•Please send comments to:
•dwhutton@umich.edu
40
41Methods: Epidemiology
RSV Hospitalization Incidence by Age and Chronic Medical
Condition “back -up slide not shown at meeting"
Source: CDC RSV -NET data from RSV seasons: 2016 -17, 2017 -18, 2018 -19, 2019 -2020
* At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, severe obesity (BMI ≥40)
** None of the above conditions. Persons may have other chronic medical conditions (e.g., heart failure, non -severe obesity, imm une compromise).050010001500200025003000350040004500RSV-associated Hospitalizations
per 100,000
Age 50-59 years Age 60-74 years Age ≥75 years

Summary: Economic Analysis of RSV Vaccination  in Adults 50 years and Older David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of Michigan 1 Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Christina Nyamuswa , MSCDC •Michael Melgar, MD •Amadea…