09 RSV Adult Hutton 508

Risk-Benefit Analysis of RSV
Vaccination in Older Adults
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
1This presentation has been corrected. See slides 13, 20, and 21 for corrected slides. The original slides are included at the  end of the presentation.
Disclaimer
•An error in the market productivity calculation for adults aged 50 –6 4
years has been identified in this presentation.
•Correction of this error and additional updates have been
inc
orporated into a more recent analysis.
•Please refer to the ACIP agenda on Ap ril 16, 2025  and the
presentation titled, “Economic Analysis of Adult RSV Vaccination, including benefits and risk discussion” by Dr. Ismael Ortega -Sanchez
for the most updated version of this analysis.
2
Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Christina Nyamuswa , M SCDC
•Michael Melgar , M D
•Amadea Britton, MD
•Lauren Roper, MPH
•Mila P rill, M SPH
•Jamison Pike, PhD
•Ismael Ortega- Sa nchez, PhD
•Andrew Leidner, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Rebecca Woodruff, PhD
•Huong Pham, MPH
3
Conflicts of interest  statements
•No known conflict of interests.
4
Objective:
•Compare the es timated benefits of RSV vaccination with the potential risk of Guillain -
Barre syndrome (GBS) after RSV vaccination in adults aged 50 -59 years with chronic
medical conditions, 60 -74 years with chronic medical conditions, and among all adults
aged 75 years and older.
•To do this, used the same mathematical models presented in previous presentation. In
ad
dition to cost effectiveness, these models estimate the burden of RSV disease,
including RSV -associated hospitalization, ICU admissions, and deaths, that might be
averted through vaccination.
•Will summarize estimated benefit outputs from those models and add information on
pot
ential rates of GBS experienced after RSV vaccination.
•This is an update to the presentation on benefits and risks from the February 2024 ACIP
mee
ting. Here, we add information on observational (“real -world”) vaccine effectiveness
against hospitalization and expand the analysis to evaluate benefits and risks specifically among adults with chronic medical conditions, including adults aged 50 -59 years.
•Focus only on the Pr
 otein subunit RSV vaccines (manufactured by Pfizer and GSK). To date,
there are no pre -licensure or observational data indicating risk of GBS after Moderna RSV
vaccination (mRESVIA). 5
Methods: Study question
•Compare the es timated benefits of RSV vaccination and the
potential risk of Guillain -Barre syndrome (GBS)  after Protein
subunit RSV vaccination (Pfizer/GSK).
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: Pro tein subunit RSV vaccines
•Pfizer’s ABRYSVO
•GSK’s AREXVY
•Comparator: Ea ch 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)
Methods: Scenario analyses
•Adults in each age group (50 -59, 60 -74, ≥75) without chronic medical
conditions*
•Adults in each age group with sp ecific  chronic medical conditions:
•Chronic obstructive pulmonary disease (COPD)
•Asthma
•Coronary artery disease
•Chronic kidney disease
•Diabetes mellitus
•Severe obesity (BMI ≥40 )
•Heart failure
•Immune Compromise
•Lung Transplant
•Hematopoietic cell transplant, allogeneic
•Hematopoietic cell transplant, autologous
8Assumed that vaccine effectiveness was
reduced by half in immune compromised
populations, compared with all others
*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40)
Heart failure and immune compromise are considered separately because RSV epidemiologic parameters were derived from differen t
published sources and cannot be combined with RSV -NET hospitalization rate estimates under “at least one” condition.
Methods: Decision Tree Model
9No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadRSV Infection
Adverse
EventsGuillain Barre Syndrome
No Guillain Barre SyndromeInfection RSV Infection
•GBS risk attributable to RSV vaccination is based on FDA active surveillance
using CMS data.
•The FDA analysis was a self -controlled case series based on inpatient claims
data.
Study population: Medicare beneficiaries ages ≥65 years1 who had received either Pfizer or
GSK RSV vaccine, from May 2023 (date of FDA approval) to October 8, 2023
Used administrative inpatient claims data to identify GBS cases occurring within a 1– 42-day
risk interval after RSV vaccination, compared with a 43 –90-day control interval
Incidence rate ratios and attributable risk were adjusted for outcome-dependent observation time, positive predictive value of inpatient claims in identifying chart -confirmed GBS, and
seasonality
10Methods: Attributable Risk of Guillain Barre Syndrome (GBS) from
RSV vaccination
Abbreviations: CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administration, 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.
Reference (Dr. Patricia Lloyd, FDA, June 2024 ACIP meeting)
•Attributable risk of GBS:
Pfizer ABRYSVO : 16 GBS cases (95% CI: 3, 29) per 1 million doses administered
GSK AREXVY : 3 GBS cases (95% CI: 0, 10) per 1 million doses administered*
•These risk estimates are in excess of  background rate of GBS. I.e., they
represent excess GBS cases beyond those that would occur in this
population without vaccination.
•This analysis remains preliminary. GBS cases identified using diagnostic coding must still undergo chart verification, and the analysis must be updated to include RSV vaccinations occurring after October 8, 2023.
•In the interim, we are using the available estimates, recognizing the associated uncertainty. We are also extrapolating from the study population (age ≥65 years) to adults aged 50 –64 years.
11Methods: Attributable Risk of Guillain Barre Syndrome (GBS) from
RSV vaccination
Abbreviations: CI = confidence interval, CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administrat ion, GBS = Guillain -Barre syndrome
* At tributable risk for GSK’s AREXVY was estimated to be 3 GBS cases (95% CI: -3, 10) per 1 million doses. For this analysis, the lo wer end of the 95% CI was
truncated at 0 to evaluate potential risk  of GBS. Potential protective effects were not evaluated.
•Results are presented as R SV outcomes avertable over 2 RSV seasons
per 1 million single- dose RSV vaccinations , and attributable GBS risk
per 1 million single- dose RSV vaccinations .
12Results: Estimated Benefits and Potential Risk
3 GBS cases
(95% CI 0– 10) Estimated RSV- associated outcomes avertable over 2
RSV seasons vs. potential cases of GBS per 1 million
vaccine doses in adults ≥75 years (general population)
16 GBS cases
(95% CI 3– 29) 4,283
13630 605
01,0002,
0003,0004,0005,0006,0007,0008,000Events AvertedGSK All Adults Age ≥75
Hospitalization ICU Stays Death3,817
561 539
08,0
7,000ed6,000t er5,000v A  s4,000t en3,000v E2,0001,000Pfizer All Adults Age ≥75
00
Hospitalization ICU Stays Death202 329 190 283 Lower Bound:This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 32.
Estimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with ≥1 chronic condition*
14*At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney
disease, severe obesity (BMI ≥40)  3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
2,839
647246
02,0004,0006,0008,000Events AvertedGSK At least one condition Age
60-74 years
Hospitalization ICU Stays Death2,530
577219
02,0004,0006,0008,000Events AvertedPfizer At least one condition Age
60-74 years
Hospitalization ICU Stays Death83 337 74 311 Lower Bound:
Estimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 50 -59 years with ≥1 chronic condition*
15*At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney
disease, severe obesity (BMI ≥40)  3 GBS cases
(95% CI 0– 10)
1,520
33183
02,0004,0006,0008,000Events AvertedGSK At least one condition Age
50-59 years
Hospitalization ICU Stays Death26 130Lower Bound:
16*At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney
disease, severe obesity (BMI ≥40)  3 GBS cases
(95% CI 0– 10)
Zoomed In1,520
331
83
05001,0001,5002,000Events AvertedGSK At least one condition Age
50-59 years
Hospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 50 -59 years with ≥1 chronic condition*
Range
199 -26
26130
Lower Bound:
Scenarios
17
Scenario 1: Estimated RSV-associated outcomes
avertable among adults without  chronic medical
conditions*
18*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity
(BMI ≥40)
Estimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults ≥75 years with none of these conditions *
19*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
1,732
189 245
02,0004,0006,000Events AvertedGSK None of these conditions
Age ≥75
8,000
Hospitalization ICU Stays Death1,544
168 218
02,0004,0006,0008,000Events AvertedPfizer None of these conditions
Age ≥75
Hospitalization ICU Stays Death84 89 73 80 Lower Bound:
40664 35
02,0004,0006,0008,000Events AvertedPfizer None of these conditions
Age 60 -74 years
Hospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with none of these conditions *
20*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
45672 39
02,0004,0006,0008,000Events AvertedGSK None of these conditions
Age 60 -74 years
Hospitalization ICU Stays DeathLower
Bound 14
16 14 39 34 Lower Bound:Lower
Bound 16This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 34.
406
6435
0100200300400500Events AvertedPfizer None of these conditions
Age 60 -74 years
Hospitalization ICU Stays Death
21*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
Lower
Bound 14Zoomed InEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with none of these conditions*
456
7239
0100200300400500Events AvertedGSK None of these conditions
Age 60 -74 years
Hospitalization ICU Stays Death1639 1434
Lower Bound:Lower
Bound 16This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 36.
Scenario 2: RSV-attributable deaths  avertable
among adults by age and presence of specific
chronic conditions
22
1,0441,6431,472
890 8041,6612,468
4491,146
443
01,0002,0003,0004,0005,0006,0007,0008,000
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Lung Transplant
Allogenic HCT
Autologous HCT
Heart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune CompromiseDeahts AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons vs.
potential cases of GBS per 1 million Pfizer ABRYSVO doses in adults 75
years and older with specific chronic conditions
2316 GBS cases
(95% CI 3– 29) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant
Lower bound is labeled if <50
544384 306 260 2153915854491,146
443
01,0002,0003,0004,0005,0006,0007,0008,000
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Age 60-74 years
Age ≥75
Lung Transplant
Allogenic HCT
Autologous HCT
Heart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune CompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons
vs. potential cases of GBS per 1 million Pfizer ABRYSVO doses in
adults 60-74 years with specific chronic conditions
2416 GBS cases
(95% CI 3– 29) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant
Lower bound is labeled if <50
1,1711,8431,652
999 902
1334391,8642,769
5031,286
497
01,0002,0003,0004,0005,0006,0007,0008,000
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Lung Transplant
Allogenic HCT
Autologous HCT
Heart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune
CompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons
vs. potential cases of GBS per 1 million GSK AREXVY doses in
adults 75 years and older with specific chronic conditions
253 GBS cases
(95% CI 0– 10) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant
Lower bound is labeled if <50
610431 344 292 241 1334391,864
6575031,286
497
01,0002,0003,0004,0005,0006,0007,0008,000
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Lung Transplant
Allogenic HCT
Autologous HCT
Heart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune
CompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons
vs. potential cases of GBS per 1 million GSK AREXVY doses in
adults 60-74 years with specific chronic conditions
263 GBS cases
(95% CI 0– 10) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant
Lower bound is labeled if <50
278133 95 98 75 1334391,864
2305031,286
497
01,0002,0003,0004,0005,0006,0007,0008,000
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Age 50-59 years
Age 60-74 years
Age ≥75
Lung Transplant
Allogenic HCT
Autologous HCT
Heart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune
CompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons
vs. potential cases of GBS per 1 million GSK AREXVY doses in
adults 50-59 years with specific chronic conditions
273 GBS cases
(95% CI 0– 10) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant
Lower bound is labeled if <5042 31 30 25 38Lower Bound:
Summary
•Estimated numbers of avertable deaths are much larger than
p
otential GBS cases for:
•Adults 75 and older
•Adults 60 -7 4 with at least one chronic condition
•Estimated numbers of avertable hospitalizations and ICU admissions a
re much larger than potential GBS cases for all age groups, for both
GSK’s AREXVY and Pfizer’s ABRYSVO.
•Estimated numbers of avertable deaths are larger, but more similar in m
agnitude, than potential GBS cases for:
•Adults 50 -5 9 with at least one chronic condition
•Adults 60 -7 4 without chronic conditions, particularly for the Pfizer ABRYSVO
vaccine
28
Limitations
•Uncertain Inputs
•RSV hospitalization incidence by age and condition
•RSV-NET represents ~9% of the United States and hospitalization rates observed in RSV -N ET may
not be generalizable to the U.S.
•Could not include all conditions that may increase risk of severe RSV disease in this analysis
•Vaccine effectiveness (VE)
•Observational VE data only available for first few months after vaccination —p rotection over time
was extrapolated from waning in efficacy against symptomatic illness observed in clinical trials
•Risk of Guillain-Barre Syndrome
•GBS risk estimates were calculated using a small number of events observed after RSV
va
ccination, resulting in high uncertainty.
•GBS was identified by diagnostic codes in administrative data and may be subject to coding er
rors. Not all cases of GBS occurring after RSV vaccination may have received a diagnostic code.
•Attributable risk of GBS may be different among adults 50 -59  than among adults 60 and older.
29
Thank You
•Please send comments to:
•dwhutton@umich.edu
30
Original slides
•The following slides contain errata. They are being shared here for
arec
ord 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 th
efollowing slides.
31
3 GBS cases
(95% CI 0– 10) Estimated RSV- associated outcomes avertable over 2
RSV seasons vs. potential cases of GBS per 1 million
vaccine doses in adults ≥75 years (general population)
3216 GBS cases
(95% CI 3– 29) 4,283
630 605
01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedGSK All Adults Age ≥75
Hospitalization ICU Stays Death3,817
561 539
01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedPfizer All Adults Age ≥75
Hospitalization ICU Stays Death254 311 232 295 Lower Bound:This slide was presented at ACIP on June 26, 2024 and contains errata (highlighted in purple). To see the corrected slide, pl ease see slide 13 ; to see the corrected slide with changes highlighted see slide 33.
3 GBS cases
(95% CI 0– 10) Estimated RSV- associated outcomes avertable over 2
RSV seasons vs. potential cases of GBS per 1 million
vaccine doses in adults ≥75 years (general population)
3316 GBS cases
(95% CI 3– 29) 4,283
630 605
01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedGSK All Adults Age ≥75
Hospitalization ICU Stays Death3,817
561 539
01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedPfizer All Adults Age ≥75
Hospitalization ICU Stays Death202 329 190 283 Lower Bound:This slide has been corrected (highlighted). To see the slide as originally presented at the June 26, 2024 meeting, please se e slide 32; to see a corrected, unhighlighted version, see slide 13 .
45672 39
02,0004,0006,0008,000Events AvertedGSK None of these conditions
Age 60 -74 years
Hospitalization ICU Stays DeathLower
Bound 14Lower
Bound 15
40664 35
02,0004,0006,0008,000Events AvertedPfizer None of these conditions
Age 60 -74 years
Hospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with none of these conditions *
34*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
15 14 39 34 Lower Bound:This slide was presented at ACIP on June 26, 2024 and contains errata (highlighted in purple). To see the corrected slide, pl ease see slide 20 ; to see the corrected slide with changes highlighted see slide 35.
45672 39
02,0004,0006,0008,000Events AvertedGSK None of these conditions
Age 60 -74 years
Hospitalization ICU Stays DeathLower
Bound 16
40664 35
02,0004,0006,0008,000Events AvertedPfizer None of these conditions
Age 60 -74 years
Hospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with none of these conditions *
35*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
Lower
Bound 14
16 14 39 34 Lower Bound:This slide has been corrected (highlighted). To see the slide as originally presented at the June 26, 2024 meeting, please se e slide 34; to see a corrected, unhighlighted version, see slide 20.
Lower
Bound 15456
7239
0100200300400500Events AvertedGSK None of these conditions
Age 60 -74 years
Hospitalization ICU Stays Death406
6435
0100200300400500Events AvertedPfizer None of these conditions
Age 60 -74 years
Hospitalization ICU Stays Death
36*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
Lower
Bound 14Zoomed InEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with none of these conditions*
1539 1434
Lower Bound:This slide was presented at ACIP on June 26, 2024 and contains errata (highlighted in purple). To see the corrected slide, pl ease see slide 21 ; to see the corrected slide with changes highlighted see 37.
Lower
Bound 16406
6435
0100200300400500Events AvertedPfizer None of these conditions
Age 60 -74 years
Hospitalization ICU Stays Death
37*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).
Persons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases
(95% CI 0– 10) 16 GBS cases (95% CI 3– 29)
Lower
Bound 14Zoomed InEstimated RSV- associated outcomes avertable over 2 RSV
seasons vs. potential cases of GBS per 1 million vaccine
doses in adults 60 -74 years with none of these conditions*
456
7239
0100200300400500Events AvertedGSK None of these conditions
Age 60 -74 years
Hospitalization ICU Stays Death1639 1434
Lower Bound:This slide has been corrected (highlighted). To see the slide as originally presented at the June 26, 2024 meeting, please se e slide 36; to see a corrected, unhighlighted version, see slide 21.

Summary: Risk-Benefit Analysis of RSV  Vaccination in Older Adults  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 1This presentation has been corrected. See slides 13, 20, and 21 for corrected slides. The original slides are included at the  end of the presentation. Disclaimer…


10 RSV Adult Ortega Sanchez 508

Economics of Respiratory Syncytial Virus (RSV)
Vaccination in All U.S. Adults≥75 years -old, and
Adults aged 60 -74 and 50-59 years
at Increased Risk
SUMMARY COMPARING MODELS FROM:
GSK,Moderna AND University of Michigan -CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, June 26, 2024
1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases
Conflict of interest
•GSK model : David Singer et al.,  [complete list and affiliations, upon request]
•GSK manufactures the adjuvanted RSVPreF3 vaccine
•RTI Health Solutions was funded by GSK
•Moderna  model : Parinaz  Ghaswalla  et al., [complete list and affiliations, upon
request]
•Moderna manufacturers the mRNA -1345 ( mRESVIA ) RSV  vaccine
•Quadrant Health Economics was funded by Moderna
•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega -
Sanchez et al. from CDC [complete list and affiliations, upon request ]
•All authors: No conflicts of interest
2
Three policy questions for economic modeling
1.Should a single dose of RSV vaccination (any licensed product) be
recommended for all adults 75+?
2.Should a single dose of RSV vaccination (any licensed product) be
recommended for adults 60 -74 at increased risk of severe RSV
disease?
3.Should a single dose of RSV vaccination (any licensed product*) be
recommended for adults 50 -59 at increased risk of severe RSV
disease?
*Only a single RSV vaccine (GSK AREXVY) is licensed for use in adults aged 50 -59 years who are at increased risk of RSV lower
respiratory tract disease.
https://www.fda.gov/vaccines -blood -biologics/arexvy
https://www.fda.gov/vaccines -blood -biologics/abrysvo
https://www.fda.gov/vaccines -blood -biologics/vaccines/mresvia
Economic analyses
Cost -effectiveness analyses :
       Comparator       Intervention
Base -case scenarios:
•What is the incremental cost-effectiveness  of vaccinating adults aged ≥75 years against RSV relative to “No
vaccination”?
•What is the incremental cost-effectiveness  of vaccinating adults aged 60 -74 years and 50 -59 years at increased risk
of severe RSV disease relative to “No vaccination”?
4Unvaccinated
age and risk groups
-All ≥75yr -olds
-Increased risk 60 -74yr -olds
-Increased risk 50 -59yr -oldsUse of a licensed RSV vaccine
among
-All ≥75yr -olds
-Increased risk 60 -74yr -olds
-Increased risk 50 -59yr -oldsPolicy
Questions
1
2
3
GSK, UM-CDC and Moderna : incremental
analyses of vaccination strategies
Policy
questionIncremental analysis GSK modelUM-CDC model
Protein Subunit             Moderna
     GSK & Pfizer                    VaccineModerna
model
1Vaccinate All ≥75yr -olds
vs.
No vaccinationReviewed in
June 2023Included Included Included
2Vaccinate Increased risk 60 -74yr -olds
vs.
No vaccinationNot
IncludedIncluded
(Eight conditions)*Included
3Vaccinate Increased risk 50 -59yr -olds
vs.
No vaccinationIncluded
(Five
conditions) **Included***
(Eight
conditions)*Not
Included***Not
Included***
No vaccination was deemed an appropriate comparator under the current shared clinical decision -making recommendation.
* Risk conditions included chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic kidney dise ase, diabetes mellitus, severe obesity (BMI ≥40),
heart failure, and immune compromise
** Conditions included in GSK model are COPD (base -case), heart failure, coronary artery disease, asthma, diabetes
*** Only a single RSV vaccine (GSK AREXVY) is licensed for use in adults aged 50 -59 years who are at increased risk of RSV lower  respiratory tract disease. As such, the economic
model used GSK -specific inputs for the 50 -59-year -old population. 5
6Modeling design and assumptions
GSK Moderna UM-CDC
Static analytical decision -making models
Sensitivity analyses (and probabilistic simulation)
 (
)
 (
)
Hypothetical populations: ≥75yrs old general population and 60 -74yrs
old at increased risk (50 -59yrs old at increased risk)(
)
 (
)
Time Frame at least 3 years after a dose of RSV vaccine*
Analytic Horizon: Age - and comorbidity -specific life expectancy**
Discount rate: 3%
Year of economic outcomes measured: 2022/2023
Societal perspective (and healthcare perspective)
 (
)
 (
)
 (
)
* Base -case in UM -CDC and Moderna models relied on a two -year time frame (three -year timeframe included in scenario analysis) wh ile GSK
used a three -year timeframe in the base -case.
In each model, selection of timeframe is based on the duration of protection assumption
** Age and comorbidity specific life expectancy were used for comorbid 50 –59-year -old in  GSK model.
GSK, Moderna  and UM-CDC models comparison:
From one -way sensitivity analyses
We will compare:
•Incidence of RSV
hospitalization and
outpatient care
•Medical and indirect
costs
•Initial vaccine
effectiveness
•Vaccine waning
•Age and risk groups
7
Moderna : Adults ≥60yrs at high risk GSK : Adults 50 -59 yrs. at high risk Base -case= $61K/QALY saved
8UM-CDC Moderna
Incidence of RSV outpatient illness
(per 100,000 persons per year)2,940 for adults ≥60 with cardiopulmonary
disease (including COPD)a
1,722 for adults ≥60 with other chronic
conditions (e.g., diabetes mellitus)b1,833  for adults 60 -64 and
2,478 for adults ≥65 years,
general population
Incidence of RSV hospitalization
(per 100,000 persons per year)Age-dependent:
198–527 for adults ≥60 with at least one
chronic conditiond
32–121 for adults ≥60 without chronic
conditionsd66.5 for adults 60 -64 and
266.7 for adults ≥65 years,
general population
Direct medical costs per RSV
hospitalizationAge-dependent:
$21,417 – $22,425,e
adjusted using median length of stay by
chronic conditions from RSV -NET$11,876
($8,407 - $47,512)f,g
a Adapted from Belongia  et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316 .
b McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300
c Adapted from McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; (Outpatient targets include both emergency department and outpatient visits)
d RSV -NET, CDC unpublished data. Crude surveillance rates were adjusted using multipliers for the frequency of RSV testing durin g each season and the sensitivity of RSV diagnostic tests.
e Ackerson et al. J Infect Dis (2020). Updated to Q3 2022$ using GDP Deflator: https://doi.org/10.1093/infdis/jiaa183 ; Branche et al. Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595
f Wyffels  V  et al (2020) A Real -World Analysis of Patient Characteristics and Predictors of Hospitalization Among US Medicare Beneficiaries with Respirat ory Syncytial Virus Infection :
https://pubmed.ncbi.nlm.nih.gov/32026380/   (range values $8,407 is from Choi and $47,512 is from Pastula )
g Merative  MarketScan  Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)Moderna  and UM-CDC models:
Key differences in model inputs, adults ≥60 years
9UM-CDC GSK
Incidence of RSV outpatient illness
(per 100,000 persons per year)2,940 for adults 50 -59 with cardiopulmonary
disease (e.g., COPD)a
1,722 for adults 50 -59 with other chronic
conditions (e.g., diabetes mellitus)b2,925
for adults 50 -59 with COPD a
Incidence of RSV hospitalization
(per 100,000 persons per year)106 for adults 50 -59 with at least one
chronic condition c
169 for adults 50 -59 with COPD, specifically c312
for adults 50 -59 with COPD d
Direct medical costs per RSV
hospitalization$20,330 for adults 50 -59,e
adjusted using median length of stay, by
chronic condition, from RSV -NET$35,308
for adults 50 -59f
a Adapted from Belongia  et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316 . Adjusted by a factor of 1.5 for PCR sensitivity (McLaughlin et al. [2022])
b McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300
c RSV-NET, CDC unpublished data. Crude surveillance rates were adjusted using multipliers for the frequency of RSV testing during each season and the sensitivity of RSV diagnostic tests.
d Adapted from Branche et al. (2022) across Rochester and New York City sites adjusted by a factor of 1.5 for PCR sensitivity  (McLaughlin et al. [2022])
e Ackerson et al. J Infect Dis (2020). Updated to Q3 2022$ using GDP Deflator: https://doi.org/10.1093/infdis/jiaa183 ; Branche et al. Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595
f CMS Medicare Inpatient Hospitals - by Geography and Service (CMS, 2023a); (DRG Average Payments from 2019 dataset); Falsey  et al. (2005); KFF (2020) GSK and UM-CDC models:
Key differences in model inputs, adults 50 -59 years
Moderna  and UM-CDC:
Initial or Early Peak of Vaccine Efficacy & Decline
10a Efficacy over median 19 months (Moderna) as reported in the phase 3 clinical trials
b Moderna phase 3 trial data; VE against medically attended acute respiratory illness
c Moderna mRNA -1345 Efficacy from the Phase 2/3 Clinical Trial for RSV -ARD (primary analysis: 1 -4 months)
d Moderna phase 3 trial data; VE against medically attended lower respiratory tract disease with ≥3 lower respiratory symptom s
e Moderna mRNA -1345 Efficacy from the Phase 2/3 Clinical Trial for RSV -LRTD with ≥2 symptoms associated with shortness of breath  (primary analysis: 1 -4 months)UM-CDC Model Moderna  Model
Moderna vaccine Moderna vaccine
Vaccine efficacy against RSV outpatient
illnessa                                                                                Year  154
(0–83)bPeak: 68.4
(50.9 –79.7)c
Year 2Linear decline reaching zero at
month 2440.1
Weighted least square regression
Vaccine efficacy against RSV hospitalization  and
emergency department visita                                                 Year 175
(0–95)dPeak: 86.7
(41.9 –97.0)e
Year 2Linear decline reaching zero at
month 2457.9
Weighted least square regression
Moderna  and UM-CDC: Assumption on waning
of vaccine effectiveness (VE) per outcome
11UM-CDC ( two-year model timeframe )
The pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 dataMODERNA ( two-year model timeframe )
ARD = Acute respiratory disease
LRTD =Lower respiratory tract disease
Est. = estimated
ED = Emergency department0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 810 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy
Month
Medically attended RSV ARD (outpatient)
Est. Medically attended RSV ARD (outpatient)
Medically attended RSV LRTI/LRTD with 3+ symptoms (ED, hospitalization)
Est. Medically attended RSV LRTI/LRTD with 3+ symptoms (ED, hospitalization)Linear decay to 0%
by 24 months75%
54%
(Outpatient and ED)
(Outpatient and ED)
(Hospitalization)
(Hospitalization)
GSK and UM-CDC:
Initial or Early Peak of Vaccine Efficacy & Decline
12a Efficacy over median 23 months follow up (GSK) as reported in the phase 3 clinical trials
b GSK phase 3 trial data; VE against medically attended acute respiratory illness
c GSK phase 3 trial data; VE against acute respiratory illness, regardless of whether medically attended. During month 1, 50%  of peak VE is assumed, with linear waning in months 2+ based on
weighted linear regression.
d Observational vaccine effectiveness, GSK -specific.
e Proportional waning applied to Season 1 efficacy, from GSK phase 3 trial efficacy against lower respiratory tract disease ( Season 2 vs. Season 1)
f GSK phase 3 trial data; VE against lower respiratory tract disease, regardless of whether medically attended. During month 1, 50% of peak VE is assumed, with linear waning in months 2+ based
on weighted linear regression.UM-CDC Model GSK Model
GSK vaccine GSK vaccine
Vaccine efficacy against RSV outpatient
illnessa                                                                              Year  179
(54–92)bPeak: 73.3
(57.9 –87.4)c
Year 2+28
(0–60)bWeighted linear regression over time
(-2.1% monthly waning)c
Vaccine efficacy against RSV hospitalization  and
emergency department visita                                                Year 184
(74–90)dPeak: 86.5
(67.7 –98.7)f
Year 2+60
(43–72)eWeighted linear regression over time
(-1.8% monthly waning)f
GSK: Residual Vaccine Effectiveness (VE) analyses
(3-year timeframe )
13RSV LRTD : 50% of peak VE ( 86.5% )
assumed in month 1, peak VE
declines by 1.8%  monthly rate
beginning in month 2 though 23 -
month follow up of trial.  Assumed
to follow linear decline trend
afterwards. Reaches 0% near month
48
RSV ARI : 50% of peak VE ( 73.3% )
assumed in month 1, peak VE
declines by 2.1%  monthly rate
beginning in month 2 though 23 -
month follow up of trial.  Assumed
to follow linear decline trend
afterwards. Reaches 0% in month 36
Source : GSK Technical report and Slides June
2024
LRTD= Lower respiratory tract disease
ARI= Acute respiratory illness
LB= Lower bound
The pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond
available phase 3 data
79%
28%78%
55%84%
60%
0%10%20%30%40%50%60%70%80%90%100%
0 6 12 18 24 30GSK vaccine efficacy
Months since vaccination
14UM-CDC: Assumption of waning of vaccine
efficacy ( GSK vaccine) ( 2-year timeframe )
The pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond available phase 3 data____
Hospitalization
(including ICU
& death)
____
Emergency
Department
visit
____
Outpatient
visit
* Target population: All adults ≥75yrs (Table 27, Moderna Technical report June13,2024)
** Target population: High -risk 60 -74yrs (Table 27, Moderna Technical report June13,2024)  Policy questions 1 & 2:  Moderna  and UM-CDC
Moderna model
Moderna vaccineUM-CDC model
Moderna vaccine
$/QALY saved (2-year
timeframe )$55,995* $66,287
$/QALY saved ( 3-year
timeframe )Not reported $42,495Policy question 1 . What is the incremental cost-effectiveness  of vaccinating alladults aged ≥75
years old against RSV illness relative  to “No vaccination”?
15Policy question 2 : What is the incremental cost-effectiveness  of vaccinating adults aged 60 -74 years old at
increased risk of severe RSV illness relative  to “No vaccination”?
$/QALY saved ( 2-year
timeframe )$89,064** $80,953
$/QALY saved ( 3-year
timeframe )Not reported $49,198
* GSK estimated cost -saving values for four high risk conditions: COPD, heart failure, CAD and Diabetes. For Asthma, GSK estimat ed societal cost of $2,445/ QALY saved
** In the base case (2 -year vaccine effectiveness timeframe), Michigan estimated a societal cost of $154,501 /QALY saved for adults with at least one chronic condition
(COPD, asthma, CAD, CKD, Severe Obesity, or Diabetes). For individual conditions, societal costs ranged from $30,720 (CKD) to $171,661 (Diabetes) per QALY sav ed.
When evaluating other specific conditions not included in “at least one” , $/QALY ranged from cost -saving (lung transplant, allogeneic hematopoietic cell transplant) to
$14,335 (heart failure) and $14,521 (autologous hematopoietic cell transplant).Policy question 3:  GSK and UM-CDC
Policy question 3:  What is the incremental cost-effectiveness  of vaccinating adults aged 50 -59
years at increased risk of severe RSV illness relative  to “No vaccination”?
16GSK* UM-CDC**
$/QALY saved ( 2-year
timeframe )Not reported $154,501
$/QALY saved ( 3-year
timeframe )Cost -saving to $2,445 $112,949
Limitations
17•Factors not considered that may result in underestimating the cost -effectiveness of RSV
vaccination
•No impact of RSV on long -term prognosis of COPD or of other higher risk conditions
•No indirect effects of vaccination (i.e., no protection against RSV transmission)
•No productivity or quality of life impact on caregivers during RSV illness
•All models partially  include RSV-related medical costs incurred after discharge from an RSV -associated
hospitalization or emergency department visit: Stay in long -term care or rehabilitation facility
•Manufacturer models partially  include potential  vaccine -associated serious adverse events (SAEs)
or from Guillain Barre syndrome (GBS): Quality of life impact, resource utilization, and costs
associated with SAEs, including GBS specifically for protein subunit RSV vaccines.
•Vaccine efficacy beyond median clinical trial follow -up time (beyond 19 months, Moderna ; or 23
months, GSK) is unknown
•All 3 models assumed non -zero declining  efficacy beyond trial time data
•All 3 models assumed seasonal vaccination (with optimal timing in the late summer and early fall)
without off -RSV-season vaccination impact.
Conclusion
18•Differences in key inputs and assumptions among GSK, Moderna  and UM-CDC models explain
differences in results:
•Annual incidence of RSV hospitalization and outpatient disease
•Initial vaccine effectiveness and waning of protection
•Medical cost per RSV hospitalization
Resulting ICERs for policy questions vary by age and high -risk group:
•1: Vaccinating all adults aged ≥75 years old against RSV illness
•Moderna  and UM-CDC models reported societal costs between $51K to $66K per QALY saved
•2: Vaccinating adults aged 60 -74 years old at higher risk of severe RSV disease
•Moderna  and UM-CDC models reported societal costs between $61K to $89K per QALY saved
•3: Vaccinating adults aged 50 -59 years old at higher risk showed more discrepant $/QALY ratios
•Outcomes ranged from societal cost-saving  (GSK) to $154K per QALY saved ( UM-CDC)
Overall, vaccination would significantly reduce RSV disease burden in adults 50 -59 and 60 -74 years
old at higher risk of RSV disease and in the general population of adults aged ≥75 years old.
•Efficacy clinical trial data and assumptions support impact on disease reduction
Acknowledgements
From NCIRD/CORVD
•Michael Melgar
•Amadea Britton
•Katherine Fleming -Dutra
Also:
•Adult RSV working group members
•Andrew Leidner and the Econ team from NCRID/ISD
19

End of Summary

Summary: Economics of Respiratory Syncytial Virus (RSV)  Vaccination in All U.S. Adults≥75 years -old, and  Adults aged 60 -74 and 50-59 years  at Increased Risk SUMMARY COMPARING MODELS FROM: GSK,Moderna AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, June 26, 2024 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for…