Document text
This slide deck was prepared by Dr. David Hutton
of the University of Michigan and reflects his work.
It is being presented by CDC staff on his behalf. Dr.
Hutton will be available to answer questions at the
end of this presentation.
1
Economic Analysis of Protein Subunit
and mRNA RSV Vaccination in Adults
aged 50 -59 Years
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
2This slide deck was prepared by Dr. David Hutton of the University of Michigan and reflects his work. It is being
presented by Dr. Ismael Ortega -Sanchez (CDC) on his behalf.
Presentation for the Advisory Committee on Immunization Practices, April 16th, 2025
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
•Amber Kautz, PhD
•Jamison Pike, PhD
•Ismael Ortega -Sanchez, PhD
•Andrew Leidner, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Rebecca Woodruff, PhD
•Gordana Derado, PhD
•Huong Pham, MPH
3
Conflicts of interest statements
•No known conflict of interests.
4
Study Question
•Evaluate the Cost -Effectiveness of RSV vaccination
•Compare vaccination to no vaccination using an incremental cost -effectiveness
ratio
•Scenario Analyses
•Perspective: Societal
•Focus: Age 50 -59
•We will show some results for other age groups as well
5
Methods
6
Methods: Intervention(s)
•Target population: US adults aged ≥50 years, stratified by age, chronic
medical conditions
•Adults aged 50 -59 years with at least one chronic medical condition*
•Adults aged 60 -74 years with at least one chronic medical condition*
•Adults aged ≥75 years
•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*For base case, at least one of: chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic
kidney disease, diabetes mellitus, severe obesity (BMI ≥40)
Methods: Decision Tree Model
8No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
Dead
Box A. RSV Infection
Methods: Decision Tree Model
9No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
Dead
Box A. RSV Infection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventGuillain Barre Syndrome
Methods: Decision Tree Model
10No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
Dead
Box A. RSV Infection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventInfection Box A. RSV Infection in each node : same
structure as above, but with risks reduced,
according to vaccine effectiveness
Guillain Barre Syndrome
Annual RSV incidence
•At least one chronic medical condition (source RSV -NET and the Behavioral Risk Factor
Surveillance System [BRFSS]):
•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 and the Behavioral Risk Factor
Surveillance System [BRFSS]):
•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 36 months
VE against hospitalization and emergency department visits was assumed to be equal to results of a meta -analysis of observational V E estimates from CDC, FDA/CMS, Veteran’s
Health Administration, and Pfizer analyses from the first RSV season of vaccine availability. VE against outpatient illness w as assumed to be the mean across the two products of
trial efficacy against RSV acute respiratory illness.3-year projected effectiveness against ED and hospitalization based
on a meta -analysis of real -world vaccine effectiveness studies. Base
case truncated at 36 months based on available clinical follow -up
extending only through 3 RSV seasons for a subunit vaccine.
68%
39%78%
59%
45%82%
62%
48%
0%10%20%30%40%50%60%70%80%90%100%
0 6 12 18 24 30 36Effectiveness
Months since vaccination
Outpatient ED Hospitalization
Unlike for protein subunit RSV vaccines, there are
still no published vaccine effectiveness results for
Moderna’s mRNA RSV vaccine.
All effectiveness assumptions in this model are
derived from clinical trial efficacy against
symptomatic disease. Median clinical trial follow up
does not extend beyond 2 years per participant.
14
Vaccine effectiveness (VE) of a single dose over time
base case : mRNA Moderna RSV vaccine ( mRESVIA )
15Linear decay to 0% by
24 months
VE against emergency department visits and hospitalization was assumed to be equal to clinical trial vaccine efficacy against RSV lower respiratory tract disease with ≥2
signs/symptoms. VE against outpatient illness was assumed to be equal to clinical vaccine efficacy against medically attended RSV acute respiratory illness. VE was assumed to
decline to zero by month 24 post -vaccination.2-year projected effectiveness based on trial efficacy data through 24
months of follow -up (no real -world effectiveness data exists).
Duration of protection may extend beyond 24 months, but base case
truncated at 24 months based on available clinical follow -up
extending only through a median of <24 months per participant.
68%
44%84%
38%
30%
0%10%20%30%40%50%60%70%80%90%100%
0 6 12 18 24 30 36Effectiveness
Months since vaccination
Outpatient ED and Hospitalization
Vaccine effectiveness (VE) of a single dose over time
scenario analysis : mRNA Moderna RSV vaccine ( mRESVIA )
3-year projected effectiveness based on waning model developed
by Moderna using clinical trial efficacy at multiple time points (no
real -world effectiveness data exists). In this model effectiveness is
projected to extend for 3 RSV seasons.
Orange line: VE: RSV -LRTD
Blue line: VE: RSV -ARD
Moderna performed a weighted least square regression on VE data estimated every 2 months, through 18 months68%84%
0%10%20%30%40%50%60%70%80%90%100%
0 6 12 18 24 30 36Effectiveness
Months since vaccination
Outpatient ED and Hospitalization
16
Methods Updates
Same model presented in June 2024 and October 2024, with the
following changes:
•Costs
•Costs for those under 65 based on an analysis using MarketScan by Averin et al.
•Marketscan (all of US)
•Matched adults 18+, also reports by chronic condition
•Averin et al analysis was conducted using final support from Pfizer Inc
•Costs for those 65 and older based on a CDC analysis of Medicare data
•Corrected productivity calculation for ages 50 -64
•Vaccine Effectiveness
•Subunit 36 months of efficacy
•Moderna long -term efficacy assumption
•Mortality
•Guillain Barre Syndrome (GBS)
Averin A, Atwood M, Sato R, Yacisin K, Begier E, Shea K, Curcio D, Houde L, Weycker D. Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase. In
Open Forum Infectious Diseases 2024 Mar (Vol. 11, No. 3, p. ofae097). US: Oxford University Press.17
Guillain -Barre Syndrome (protein subunit
vaccines only)
•Base: FDA analysis of adults 65+ with rates ranging between 0 – 18 excess
cases per million doses administered
•Scenario:
•Baseline GBS rates in U.S. adults 50 -64 (assumed same for adults 50 -59 in the model)
•25.2 per million person -years (combined male, female)
•2021 study of 50 million person -years of observation1
•Inpatient and emergency department results, adjusted downward by the positive predictive
value (55%) of ICD codes in identifying “true” GBS in inpatient/ED.
•Relative measures of GBS risk from protein subunit RSV vaccination applied relative to
the assumed 50 -59 baseline to see what happens if risk is lower in younger adults2
•GSK: Incidence rate ratio (IRR) = 2.46 (95% CI 1.19 – 5.08)
•Pfizer: IRR = 2.02 (95% CI 0.93 – 4.40)
•42-day risk window used in FDA’s analysis.
•Net Excess 42 -day risk of 3.6 per million doses (average of Pfizer and GSK)
1. Shui IM, Rett MD, and Weintraub E et al. Guillain -Barré syndrome incidence in a large United States cohort (2000 -2009).
Neuroepidemiology. 2012;39(2):109 -15. doi: 10.1159/000339248. Epub 2012 Jul 28. PMID: 22846726.
2. Package inserts: GSK, Pfizer.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 2024
19Hutton, 2023. “Economic Analysis of RSV Vaccination in Older Adults”. June 2023 ACIP Meeting
Hutton et al., 2024. “Cost -effectiveness of vaccinating adults aged 60 years and older against respiratory syncytial virus”. Vaccine
42(24): 126294
Methods: Scenarios
•Manufacturer -specific (Pfizer and GSK -specific models; Moderna
is considered separately in the base case, so no scenario needed)
•For Moderna, assuming longer duration of protection
(manufacturer 3 -year efficacy assumption)
•Vaccination of persons without chronic medical conditions
•Condition -specific (e.g., vaccination of persons with heart failure)
•Public sector prices for each vaccine (Federal Supply Schedule
prices from the Veterans Health Administration*), rather than the
manufacturer list price
20 *https://www.vendorportal.ecms.va.gov/NAC/Pharma/List
Results
21
Previous (June 2024) Cost -Effectiveness Results: Societal
costs per quality -adjusted life year (QALY) gained
PreF subunit vaccines PreF mRNA vaccines
Adults aged 50 -59
years with at least
1 condition$154,501*
Adults aged 60 -74
years with at least 1
condition$60,933 $80,953
All adults aged ≥75
years $51,447 $66,287 2-year 2-year
At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes
mellitus, chronic kidney disease, severe obesity (body mass index [BMI] ≥40)
*The $154,501 incremental cost -effectiveness ratio (ICER) is GSK -specific, but the other two are for subunit in
general. 22
Today’s Cost -Effectiveness Results:
Societal costs per quality -adjusted life year (QALY) gained
PreF subunit vaccines PreF mRNA vaccines PreF mRNA vaccines
Adults aged 50 -59
years with at least
1 condition$43,070
(<0-$266,769)$152,293
($1,154 -$811,138)$95,182
(<0-$682,508)
Adults aged 60 -74
years with at least 1
condition$21,721
(<0-$120,989)$85,781
($3,368 -$409,467)$50,864
($3,668 -$249,938)
All adults aged ≥75
years$45,769
($25,505 -$84,871)$100,571
($58,277 -$225,885)$70,731
($42,069 -$159,451)3-year 2-year 3-year
At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease,
diabetes mellitus, chronic kidney disease, severe obesity (body mass index [BMI] ≥40)
Ranges reflect 2.5th and 97.5th percentile from Monte Carlo simulation.
“<0” represents cost -saving (lower costs, improved health/QALYs) 23
Outcome Subunit
(3-year)mRNA
(2-year)mRNA
(3-year)
Outpatient 43 56 62
Hospitalization 510 933 681
Death 7,985 14,620 10,675 Number Needed to Vaccinate to Prevent One Outpatient Visit,
Hospitalization, or Death
Age 50 -59 years with at least one condition
At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease,
diabetes mellitus, chronic kidney disease, severe obesity (body mass index [BMI] ≥40)
24
Scenario Analyses
25
Scenario: Cost -Effectiveness Results Using Veterans
Affairs (VA) Federal Supply Schedule (FSS) Vaccine Prices:
Societal costs per quality -adjusted life year (QALY) gained
Subunit RSV
vaccinePreF mRNA vaccines PreF mRNA vaccines
Adults aged 50 -59
years with at least
1 condition$25,967 $79,443 $37,082
Adults aged 60 -74
years with at least 1
condition $12,122 $43,670 $18,380
All adults aged ≥75
years
$37,536 $64,251 $42,8823-year 2-year 3-year
VA Federal Supply Schedule prices used in lieu of list prices ( VA National Acquisition Center Contract Catalog Search Tool ): Arexvy (GSK)
$263, Abrysvo (Pfizer) $258, mResvia (Moderna) $204.
At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease,
severe obesity (body mass index [BMI] ≥40)26
$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
Heart Failure
With lung transplant
With allogenic HCT
With autologous HCTIncremental cost per QALY gained
50-59
60-74
≥75
not age-specificSpecific Chronic Conditions: Subunit
CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; BMI: body mass index; CAD: coronary artery disease; HCT: hematopoietic cell transplant
*Indicates cost saving which means net costs are reduced and health outcomes are improved when compared to “no vaccination ”
At least one condition refers to: COPD, asthma, CAD, diabetes mellitus, CKD, severe obesity (BMI ≥40)*****
27**
*
**
*
**
*
**Severe obesity (BMI ≥ 40)
Heart failure
Specific Chronic Conditions: mRNA (2 -year)
CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; BMI: body mass index; CAD: coronary artery disease; HCT: hematopoietic cell transplant
*Indicates cost saving which means costs are reduced and health outcomes are improved
At least one condition refers to: COPD, asthma, CAD, diabetes mellitus, CKD, severe obesity (BMI ≥40)*
*
28**$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
Heart Failure
With lung transplant
With allogenic HCT
With autologous HCTIncremental cost per QALY gained
50-59
60-74
≥75
not age-specificSevere obesity (BMI ≥ 40)
Heart failure
Specific Chronic Conditions: mRNA (3 -year)
CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; BMI: body mass index; CAD: coronary artery disease; HCT: hematopoietic cell transplant
*Indicates cost saving which means costs are reduced and health outcomes are improved
At least one condition refers to: COPD, asthma, CAD, diabetes mellitus, CKD, severe obesity (BMI ≥40)*
*
29***
**
***$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
Heart Failure
With lung transplant
With allogenic HCT
With autologous HCTIncremental cost per QALY gained
50-59
60-74
≥75
not age-specificSevere obesity (BMI ≥ 40)
Heart failure
Hospitalizations, ICU stays, and deaths preventable
if 20% of all U.S. adults aged 50 -59 years with at
least one chronic condition* were vaccinated
The model assumed 0–48 cases of Guillain -Barre Syndrome total
305,219
1,148
3331,793
394 8910,077
2,217
702
02,0004,0006,0008,00010,00012,000
Hospitalizations ICU Stays DeathsEvents Preventable
*At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease,
severe obesity (body mass index [BMI] ≥40)
Scenario (lower GBS risk in adults aged <65)*: Hospitalizations,
ICU stays, and deaths preventable if 20% of all U.S. adults aged
50-59 years with at least one chronic condition** were vaccinated
The model assumed 1 –29 cases of Guillain -Barre Syndrome total
*Assuming lower baseline risk of GBS in adults aged 50 -59 years than in adults aged ≥65 years. In this scenario, the relative risk of GBS
was applied to published background rates of GBS for this age group.
**At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic
kidney disease, severe obesity (body mass index [BMI] ≥40)
315,219
1,148
3331,793
394 8910,077
2,217
702
02,0004,0006,0008,00010,00012,000
Hospitalizations ICU Stays DeathsEvents Preventable
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.
•Uncertain inputs
•RSV burden of disease, especially hospitalization and mortality
•RSV costs
•Caregivers of persons ill with RSV may incur additional productivity losses not included
in this model
•Duration and waning pattern of vaccine protection (especially mRNA)
32
Conclusions
•Cost -Effectiveness of vaccinating adults 50-59 with at least one
chronic medical condition:
•Subunit: $43,070/QALY
•mRNA: $152,293/QALY (2 -year), $95,182/QALY (3 -year)
•Vaccinating people with th e following conditions may be cost -saving:
•Immune compromise, defined as hematopoietic cell transplant or lung transplant
•Heart failure
•Chronic obstructive pulmonary disease (COPD)
•Chronic kidney disease
•Severe obesity (body mass index [BMI] ≥40)
•Scenarios with lower prices were more cost -effective
33
Thank You
•Please send questions/comments to:
•[email protected]
34