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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