Document text
Economics of Vaccinating U.S. Adults ≥60
years-old against
Respiratory Syncytial Virus
A SUMMARY REPORT COMPARING MODELS FROM:
GSK,Pfizer AND University of Michigan -CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, February 23, 2023
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 : Daniel Molnar et al., [complete list and affiliations, upon request]
•GSK manufactures the adjuvanted RSVPreF3 vaccine
•RTI Health Solutions was funded by GSK
•Pfizer model: Derek Weycker et al., [complete list and affiliations, upon request]
•Pfizer manufacturers the bivalent RSVpreF vaccine
•Policy Analysis Inc. was funded by Pfizer
•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega-
Sanchez et al. from CDC [complete author list and affiliations, upon request ]
•All authors: No conflicts of interest
2
Economic analysis
Policy questions: Should adults ≥60 years of age (or ≥65 years of age) receive
one dose of Respiratory Syncytial Virus (RSV) vaccine (GSK or Pfizer product) for
the prevention of RSV disease and its complications?
Question: Is vaccinating adults aged ≥65 years (or ≥60 years) against RSV cost-
effective ?
Comparator
Unvaccinated
≥65yr -olds
(or ≥60yr -olds)Intervention
Vaccinating≥65yr -olds
(or ≥60yr -olds)
B
ase-case scenario: What is the incremental cost -effectiveness of vaccinating adults aged
≥65 years (or ≥60 years) using RSV vaccine relative to “No vaccination”?
3
Focus on key features for model comparison
•Modeling approach
•Targeted population(s)
•Perspective (healthcare vs. societal)
•Intervention strategy and comparator
•Inputs for RSV disease burden, vaccine efficacy, and costs
•Incidence of RSV disease, rates of outcomes
•Direct and Indirect costs of RSV disease
•Intervention: Vaccine efficacy, duration of protection, safety and program
costs
•Assumptions
•Strong, influential assumptions
4
5Modeling design and assumptions
GSK Pfizer UM-CDC
Static analytical decision-making models ✔ ✔ ✔
Sensitivity analyses (and probabilistic simulation)✔(✔)✔(✔)✔
Hypothe tical popul ation ≥65yrs-old (and ≥60-yrs-old)✔(✔)✔(✔)✔(✔)
Time Frame: at least 1 yr. after a dose of RSV vaccine✔ ✔ ✔
Analytic Horizon: Age-specific Life Expectancy✔ ✔ ✔
Discount rate: 3% ✔ ✔ ✔
Year of econom ic outcomes measured: 2022✔ ✔ ✔
Societal perspective (and healthcare perspective)✔(✔)✔(✔)✔(✔)
6Inputs and main outcomes
Prevention of:
•Outpatient visits for RSV
•RSV hospitalizations
•RSV-associated deaths
QALYs saved$/QALY saved
Number needed to
vaccinate (NNV) to avert an: •Outpatient visit for RSV
•RSV hospitalization
•RSV-associated death
GSK Pfizer UM-CDC
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
HCRU = health care resource use
UMich -CDC: Scenario analysis for age group,
$100 vaccine cost and vaccine candidate
7$230
$181
$155
$104 $234
$189
$166
$117
$- $50 $100 $150 $200 $250
age ≥60 years age ≥65 years age ≥70 years age ≥75 years Incremental Cost per QALY saved
Thousands
Age Group VaccinatedGSK Pfizer
GSK, Pfizer and UM-CDC models comparison:
Selected outcome ratios for RSV vaccines
8UM-CDC
model
Vac Price
$100GSK
model
Vac Price
$148
$ / QALY gained
Vaccinating adults ≥65 yrs. 180,720 68,489
Vaccinating adults ≥60 yrs. 229,895 78,971
$ / hospitalization averted
Vaccinating adults ≥65 yrs. 101,406 57,114
Vaccinating adults ≥60 yrs. 133,992 69,638GSK vaccine
UM-CDC
model
Vac Price
$100Pfizer
model
Vac Price
$200
$ / QALY gained
Vaccinating adults ≥65 yrs. 189,407 43,749
Vaccinating adults ≥60 yrs. 233,779 50,197
$ / hospitalization averted
Vaccinating adults ≥65 yrs. 122,886 19,845
Vaccinating adults ≥60 yrs. 161,310 23,271Pfizer vaccine
UM-CDC model : One-way Sensitivity Analyses
Base case: Age ≥65yrs $180,720/QALY (GSK), $189,407/QALY (Pfizer)
9One Year Time Horizon
*
At lower bound of Pfizer vaccine efficacy (VE =6.3%), the ICER rises to >$574 Thousand /QALY$0 $100 $200 $300 $400
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
GSK Vaccine Effectiveness LRTD
Incidence of outpatient visits for RSV
Cost per Hospitalization
Mortality, adults hospitalized with RSV
GSK Vaccine Effectiveness ARI
ED Incidence
QALYs lost Injection Site ReactionGSK: $/QALY saved ( in thousands )
Low Assumption High Assumption$0 $100 $200 $300 $400
Pfizer Vaccine Effectiveness LRTD
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
Pfizer Vaccine Effectiveness ARI
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
Cost per Hospitalization
ED Incidence
Probability of Serious Adverse EventPfizer: $/QALY ( in thousands )
Low Assumption High Assumption*
GSK model : One-way Sensitivity Analyses
Base case: Age ≥60 years; $ 78,971 /QALY saved
Average annual incidence of first RSV ARI event
Percentage of RSV LRTD cases resulting in hospitalization
Efficacy against RSV LRTD: Waning rates first vaccination with RSVPreF3 vaccine <24 months
Probability of death given RSV LRTD
Proportion RSV LRTD within first RSV ARI event
Vaccination costs per administered dose with RSVPreF3 vaccine -Purchase cost per dose – Cost
RSVPreF3 vaccine: Peak % efficacy after first vaccination against RSV LRTD caused by first RSV
infection
Baseline QALYs -General population
Efficacy against RSV ARI: Waning rates first vaccination with RSVPreF3 vaccine <24 months
Probability of AE 'Grade 3 ' after first or revaccination with RSVPreF3 vaccine
10
Pfizer model : One-way Sensitivity Analyses
Base case: Age≥60 years: $50,104/QALY saved
11
Base case
GSK, Pfizer and UM-CDC models comparison:
Selected inputs
12•RSV-hospitalization rate
GSK: Proportion of MA RSV hospitalized cases identified by PCR, differentiated by age ( Belongia, 2018)
Pfizer : Differentiated by age and comorbidity profile (Pfizer data on file)
CDC: Differentiated by age (four RSV seasons in CDC RSV-NET data)
•Unitary medical cost of RSV outcomes
•GSK: Age -& outcome specific cost for symptomatic RSV LRTD & URTI cases (MA and non -MA) (CMS)
•Pfizer: Age-, outcome- & comorbidity -specific cost for MA RSV
•CDC: Age -& outcome -specific cost for MA RSV
•Initial VE & waning over time
GSK: Phase 3, monthly waning: ARI (5.36%), LRTD (2.63%) until 12mos, then to 0%
Pfizer: Phase 3, flat 7mos, then linear decay to 0% at 24mos
CDC: GSK’s & Pfizer’s phase 3, flat 6mos, exponential decay until 12mos, then to 0%
MA = medically attended, ARI = acute respiratory infection
13UM-CDC GSK Pfizer
Incidence of RSV outpatient
illness (per 100,000 persons per year)1,519
(base- case for adults ≥65 years)a1,348
(for adults ≥65 years)b2,430
(base case for adults
≥65 years)c
Incidence of RSV hospitalization (per 100,000 persons per year)108
(base- case for adults ≥65 years)d256
(for adults ≥65 years)b,e300
(base- case for adults
≥65 years)c
Direct medical costs per RSV hospitalization$20,330 –$21,339
(age- dependent)f$13,112 –$26,224
(age- dependent)g,h$12,048 –$38,380
(age- and comorbidity -
dependent)h,i
a McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; unadjusted for under -detection of RT -PCR testing
b Adapted from Belongia et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316
c McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; Ramirez et al. (under review)
d RSV -NET, CDC unpublished data
e Adapted from Falsey et al. NEJM (2005): https://doi.org/10.1056/nejmoa043951 ; Herring et al. Vaccine (2022): https://doi.org/10.1016/j.vaccine.2021.12.002
f Ackerson et al. J Infect Dis (2020): https://doi.org/10.1093/infdis/jiaa183
g CMS Medicare Inpatient Hospitals (DRG Average Payments from 2019 dataset)
h Kaiser Family Foundation (How much more than Medicare do private insurers pay? 2020): https://www.kff.org/medicare/issue-brief/how -much -more-than -medicare-do -private -insurers -pay -a-
review -of-the-literature/
i Merative MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)GSK, Pfizer and UM-CDC models: Key differences in
model inputs
GSK model : Sensitivity of Cost per QALY saved to RSV -
Related Hospitalization Rates among Adults ≥60 years
14S8: Branche et al. (2022b; high BoD
season [New York City, 2018 -2019]);
S9: Branche et al. (2022b; low BoD
season [Rochester, 2019 -2020]);
S10: Zheng et al. (2022; low SES);
S11: Zheng et al. (2022; medium SES); S12: Zheng et al. (2022; high SES); S13: McLaughlin et al. (2022;
unadjusted);
S14: McLaughlin et al. (2022; adjusted);
S15: Widmer et al. (2012);
S16: Herring et al. (2022; Belongia et al.
[2018] estimate); S17: Herring et al. (2022; Falsey et al.
[2005] estimate); S18: DeMartino et al. (2022);
S19: Fust et al. (2022a and 2022b).
Note: BoD = burden of disease; SES = socioeconomic status.
* Derived from GSK modeling results.
S3:
S6:
S1:
S7:S5:
S4:
S2:
Base- casePfizer model : Sensitivity of Cost per QALY saved to RSV -
Related Hospitalization Rates among Adults ≥60 years
15• S1: Pooled unadjusted rates from
McLaughlin et al. (active prospective
surveillance studies only)1
• S2: Based on pooled adjusted rates from
McLaughlin et al. 1.5 -fold (active
prospective surveillance studies only)1
• S3: Rates in Rochester, NY , averaged
across all study years, from Branche et al.2
• S4: Rates in New York, NY , averaged
across all study years, from Branche et al.2
• S5: Rates averaged across all study years
and accounting for the proportion of RSV-
confirmed cases treated in hospital from
Belongia et al.3
• S6: Rates based on Matias et al.4
• S7: Rates based on Widmer et al.5
Base Case : Ongoing unvetted prospective
study with adjusted RSV detection rates of 1.6-to 1.7-fold. Pfizer Inc. data on file 1. McLaughlin JM, et al. Open Forum Infectious Diseases . 9(7), 2022
2. Branche AR et al. Clinical Infectious Diseases. 2021;74(6):1004- 1011.
3. Belongia et al. Open Forum Infect Dis . 2018;5(12):ofy316.
4. Matias et al. BMC Public Health. 2017;17(1):271.
5. Widmer et al. Influenza and Other Respiratory Viruses . 2014;8(3):347-352.
UM-CDC model : Sensitivity of Cost per QALY saved to RSV -
Related Hospitalization Rates among Adults ≥65 years
16Base case: mean value of the burden adjusted rate over RSV seasons: 2015 -16, 2016- 17, 2017- 18, and 2018- 19. Adjusted rate for 95% sensiti vity of PCR testing. CDC RSVnet
Lower bound: mean of lower confidence limit estimates across all 4 seasons assuming 95% sensitivity of PCR testing.
Upper bound: mean of upper confidence limit estimates across all 4 seasons assuming 71% sensitivity of PCR testing.$180,720 $189,407
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000
0 50 100 150 200 250 300 350Incremental Cost per QALY saved
Incidence of RSV Hospitalization per 100,000 persons per yearGSK
Pfizer
Incidence Range
Minimum
Base Case
Higher Incidence
Scenario
GSK, Pfizer and UM-CDC: Initial or Early Peak
of Vaccine Efficacy
17a VE over mean 6 –7 months of follow up in phase 3 clinical trials
b Manufacturer phase 3 trial data; VE against medically attended acute respiratory illness
c GSK phase 3 trial data; IDWeek abstract ; VE against acute respiratory illness, regardless of whether medically attended
d Manufacturer phase 3 trial data; GSK: VE against medically attended lower respiratory tract disease; Pfizer: VE against medica lly attended lower respiratory tract illness with ≥3 lower
respiratory symptomse Manufacturer phase 3 trial data; GSK: IDWeek abstract
VE against lower respiratory tract disease, regardless of whether medically attended; Pfizer: IDWeek abstract VE against lower
respiratory tract illness with ≥3 lower respiratory symptoms, regardless of whether medically attended (95% CI applied)UM-CDC GSK Pfizer
GSK vaccine Pfizer vaccine
Vaccine efficacy (VE) against RSV
outpatient illnessa79.0
(54.3– 91.5)b69.2
(30.0– 88.0)b71.7
(56.7– 82.3)c69.2
(30.0– 88.0)b
VE against RSV hospitalization and emergency department visit
a87.5
(58.4– 96.2)d80.0
(6.3– 97.9)d82.6
(57.9– 94.1)e85.7
(37.9– 98.4)e
GSK, Pfizer and UM-CDC: Assumption on
waning of vaccine efficacy (VE) per outcome
18GSKVE peaks at 2 months then wanes per month
RSV-ARI = 5.36% points per month (range: 0.00 -
13.37%) RSV-LRTD = 2.63% points per month (range: 0.00 -
10.95%)No residual protection after 12 monthsPfizerInitial VE assumed to persist for 7 months, Then to decline linearly to 0% effectiveness at 24 monthsResidual though declining protection up to 24
monthsUM-CDCVaccine and outcome -specific
For both vaccines:
Exponential decay up to 12 months and then 0% afterwards; calibrated such that the
first 6 months VE equals the trial estimate
Pfizer : Impact of vaccine’s duration of protection
(DoP) assumption on ≥65yrs Cost per QALY saved
19
Base- Case
Base- Case*
* RSV hospitalization incidence labelled “CDC x1.4” used data presented by CDC at IDWeek 2022 (Havers et al. https://doi.org/10.1093/ofid/ofac492.1828 ),
upwardly adjusted by a factor of 1.4 (based on Zhang et al. https://doi.org/10.1128/jcm.01701 -16).
Comparison of GSK and Pfizer vaccines: base case &
scenario $/QALY results using UM-CDC model
20aRecommendation = vaccination at age ≥65 years; vaccine unit cost = $100; incidence rates of RSV outcomes unadjusted for incre ased diagnostic yield from testing
in addition to RT -PCR on a respiratory specimen; vaccine efficacy only considered for one year post -vaccination
b Base case incidence rates adjusted upward for increased diagnostic yield from testing in addition to RT -PCR on a respiratory s pecimen (1.5x for outpatient illness
[McLaughlin et al; Open Forum Infect Dis (2022)], 1.4x for inpatient illness [Zhang et al; J Clin Microbiol (2016)])Scenario GSK Pfizer
Vaccine cost $200 per dose (one year time frame) $374,530 $384,267
Vaccinating adults aged ≥60 years $229,895 $233,779
Medical cost for hospitalization (lower bound) $199,018 $205,236
Base case a (Vaccine Price $100, 1 year time frame) $180,720 $189,407
Higher incidence of RSV b $91,028 $104,160
Vaccine cost $50 per dose (one year time frame) $85,815 $91,977
Limitations
21•Factors not considered that may result in overestimating the ICER
(underestimating the cost -effectiveness) of RSV vaccination
•None of the 3 models included RSV- related medical costs incurred after
discharge from an RSV- associated hospitalization or emergency department
visit:
•Stay in long-term care or rehabilitation facility
•Assisted living at home
•Productivity losses incurred by caregivers whose support is needed post-discharge
•All of the 3 models assumed no indirect effects of vaccination (i.e., no protection against RSV transmission)
•Vaccine efficacy beyond clinical trial follow -up time (6 –7 months) is unknown
•All 3 models assumed non- zero declining efficacy beyond 6– 7 months
(UM-CDC : 12 months, GSK: 12 months, Pfizer : 24 months ).
Conclusion
22•Differences in key inputs among GSK, Pfizer and UM-CDC models explain differences in results:
•Incidence of hospitalization
•Duration of vaccine efficacy
•Medical costs
•Vaccine costs
•Assumptions and selection of input data were crucial in differences in ICERs
•Adjustment approach of incidence rates of Hospitalization, ER and Outpatient
•Selection of medical costs sources and data extraction approach
•Base-case in the 3 models:
•Vaccination would significantly reduce RSV disease burden in older adults
•VE clinical trials data and assumptions support impact on disease reduction
•Economic value of RSV vaccines appear to be costly and could be cost-effective
•RSV incidence, related healthcare costs, initial VE and duration combined with reasonable
vaccine price would determine the cost-effectiveness value of RSV vaccination
Acknowledgements
From NCIRD/CDC
•Michael Melgar
•Jamison Pike
•Fiona Havers
•Meredith McMorrow
A
lso:
•Adult RSV working group members
•Econ Team members at ISD/NCIRD
23
End of Summary