Document text
Economic Analysis of RSVpreF
Maternal Vaccination
David W. Hutton, PhD, MS
Professor, Health Management and Policy, School of Public Health
Professor of Global Public Health, School of Public Health
Professor, Industrial and Operations Engineering, College of Engineering
University of MichiganSeptember 22, 2023
Research team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill, MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming -Dutra, MD, FAAP
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
•Andrew Leidner , PhD
2
Conflicts of interest statements
•Authors have no known conflict of interests.
3
•Additional vaccine efficacy scenario
•Additional timing scenarios
•Months of year to administer
•32 Τ07-36 Τ67weeks gestation
•Updated cost/doseUpdates Since June 21 Presentation
Economic Analysis of RSV Vaccination in Older Adults, June 21, 2023
0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI Against hospitalization
5Methods: RSVpreF efficacy
average 6 -month efficacy = efficacy against
hospitalization or medically -attended RSV -
associated LRTI
Zero efficacy
Source: Kampmann et al 2023
LRTI= Lower respiratory tract infection
0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI Against hospitalization
6Methods: RSVpreF efficacy
alternate flat scenario
Zero efficacy
Source: Kampmann et al 2023
LRTI= Lower respiratory tract infectionaverage 6 -month efficacy = efficacy against
hospitalization or medically -attended RSV -
associated LRTI
0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
severe MA RSV LRTI MA RSV LRTI
7Methods: RSVpreF efficacy
Optimistic scenario: Severe Efficacy with VE to 9 months
6-month efficacy against
Severe MA RSV LRTI
Zero efficacy
at 9 months6-month efficacy against
MA RSV LRTI
MA: Medically -attended, LRTI: Lower Respiratory Tract Infection
Methods: Provision of RSVpreF
8•Base case:
•Year round
•Scenarios
•Individual Months
•Ranges of Months
•April -February
•May -February
•June -February
•August -January
•September -January
•September -December
•Mother vaccinated
•During 32 Τ07-36 Τ67weeks gestation, evenly distributed
•Birth
•Must be >2 weeks after vaccination for protective efficacy to pass to infant,
based on historical gestational age
9Methods: Provision of RSVpreF
Methods: Provision of RSVpreF
10In Time= >2 weeks prior to delivery100 Pregnant persons50
No intention
50
Intend to Vaccinate
45
Vaccinated
in time2
Birth before vaccinationUptake
Timing48
Vaccinated3
Vaccinated < 2 weeks
before delivery
Results: Base case
11•Base case:
•Population of annual US births ( 3.66 million )
•50% intended uptake in the RSVpreF group
•First RSV season
•$295/dose
•RSVpreF only impacts lower respiratory tract infections
Results: Number Needed to Vaccinate
12Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group40 115 242 1,100
45 367
- 200 400 600 800 1,000 1,200
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Vaccinate to avoid
RSVPreF
Results: Costs
13Base costs of RSVpreF : $295/dose, both natural history and RSVPreF involve palivizumab for high -risk childrenCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group$0$500$1,000$1,500$2,000$2,500
Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF Natural
HistoryRSVPreF
Intervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort
Millions
Medical Productivity
Results: Cost per Event Averted
14Base costs of RSVpreF : $295/dose$11,337 $32,652 $68,423 $311,013
$12,671 $103,671
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
RSVPreF
Results: Cost -Effectiveness
15Base costs of RSVpreF : $295/dose
QALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($) QALYs lostICER ($/QALY)
Vs. NH
Natural History 1,585,172,002 18,151
RSVpreF 2,103,215,047 16,857 400,304
$0 $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000
Probability of Prematurity
RSV QALYS Lost
RSVpreF vaccine cost/dose
Disease-specific inpatient costs (per inpatient case)
Vaccination Efficacy, Hospitalized RSV LRTI through 180 days
Vaccination Efficacy, RSV MA-LRTI through 180 days
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months
Proportion of RSV infections with an LRTI diagnosis ED Visits Age 0-5 months
Proportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months
RSV mortality per hospitalization Age 0-5 monthsIncremental Cost -Effectiveness Ratio
Low HighSensitivity: Tornado RSVpreF
16Base cost of RSVpreF : $295/dose
MA= Medically -attended
LRTI= Lower respiratory tract infection
QALY= Quality adjusted life year$1.3 million
Methods: RSVpreF efficacy
“flat efficacy” scenario
17Overall Costs ($) QALYs lost ICER ($/QALY)
Natural History 1,585,172,002 18,151
RSVpreF 2,094,993,469 16,757 365,669
Slightly lower costs with
RSVpreF , slightly fewer
QALYs lost, slightly lower
ICER
ICER: Incremental cost -effectiveness ratio
LRTI= Lower respiratory tract infection
Sensitivity Analysis: More Optimistic Efficacy
18Base costs of RSVpreF : $295/dose
QALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($) QALYs lostICER ($/QALY)
Vs. NH
Natural History 1,585,172,002 18,151
RSVpreF 2,056,423,553 16,504 286,179
Higher and longer efficacy
MA: Medically -attended, LRTI: Lower Respiratory Tract Infection
19Sensitivity: Varying Efficacy, Hospitalization Cost, and
Mortality
Base$0$100,000$200,000$300,000$400,000$500,000
$0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000ICER
Hospitalization Cost
0.1% Mortality, Base Efficacy 0.1% Mortality, Optimistic Efficacy
1.0% Mortality, Base Efficacy 1.0% Mortality, Optimistic Efficacy
$- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000
$0 $50 $100 $150 $200 $250 $300 $350 $400 $450 $500ICER
Cost per dose of RSVpreFSensitivity: Cost RSVpreF
20Base Case
Results: RSVpreF timing scenarios
21•Scenarios
•Base: vaccine given year -round
•By Month
•During April -February
•During May -February
•During June -February
•During August -January
•During September -January
•During September -December
Results: RSVpreF timing scenarios
$351,238 $333,255
$181,649
$115,445 $111,248 $174,344
$- $100,000 $200,000 $300,000 $400,000 $500,000
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecICER ($.QALY)ICER: RSVpreF vs. Natural History
22Month of administration
Results: RSVpreF timing scenarios
$400,304
$363,344
$322,594
$282,498
$186,256 $167,280 $141,806
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
Base Apr-Feb May-Feb Jun-Feb Aug-Jan Sep-Jan Sep-DecICER ($.QALY)ICER: RSVpreF vs. Natural History
23
Limitations
•Model Structure
•No risk groups
•No dynamic transmission. No impact of the vaccine on transmission and
indirect effects
•Uncertain inputs
•RSVpreF cost
•QALYs lost
•Upper respiratory tract infections
•Prematurity
•Assumption: no infants will be receiving nirsevimab
24
Summary
•RSVpreF may improve RSV outcomes, but will also increase costs
•RSVpreF has the potential to be cost -effective
•Results sensitive to:
•Rate of prematurity
•Cost per dose (~65,000 –68$/QALY)
•Hospitalization Costs (Cost -saving –440,000 $/QALY)
•Efficacy (~280,000 –680,000 $/QALY)
•QALYs lost (~100,000 –800,000 $/QALY)
•Month of Administration (~110,000 –Millions $/QALY)
25QALY: Quality -Adjusted Life -Year
Economics of combined use of Pfizer
maternal RSVpreF vaccine and
nirsevimab
David W. Hutton, PhD, MS
Professor, Health Management and Policy, School of Public Health
Professor of Global Public Health, School of Public Health
Professor, Industrial and Operations Engineering, College of Engineering
University of MichiganSeptember 22, 2023
•On August 3, 2023, the Advisory Committee on Immunization
Practices (ACIP) recommended use of nirsevimab
•How should we think about combinations of RSVpreF and
nirsevimab ?
•If we know RSVpreF has been administered in time, how cost -effective is it to
provide nirsevimab ?
•If we know the infant will receive nirsevimab , how cost -effective is it to
provide RSVpreF ?Methods: Study questions
•RSVpreF will be administered in weeks 32 -36
•Because of this, we are assuming the infant is full -term, and therefore, there is no need for
palivizumab for any newborns considered in this analysis
•Consideration of higher -risk populations (but assuming they are not premature)
•New timing of RSVpreF administrationUpdates since June
Methods: Intervention effectiveness
•NO evidence of efficacy on the combined use of these products
•Assumption:
•Efficacy equal to the highest of nirsevimab or RSVpreF :
•Efficacy would not be higher than from the most effective product
29
0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both NirsevimabMethods: Intervention effectiveness
30
Additional benefit of adding nirsevimab
* Assuming administration of nirsevimab at birth
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Hospitalization Efficacy
Month
Both RSVpreF OnlyMethods: Intervention effectiveness
Example: Off -peak (Aug) birth
Additional benefit of adding nirsevimab
Note: Peak infections are typically Dec -Feb
31
Incremental benefit of adding nirsevimab on top of
RSVpreF
32•For infants of persons vaccinated with RSVpreF during pregnancy at
least 2 weeks prior to delivery
Results: Incremental benefit of adding nirsevimab
on top of RSVpreF : Higher Risk
•Higher -Risk
•Increased multiplier on
•risk of hospitalization
•No change in
•Outpatient incidence
•ED incidence
•Cost/outcome
•QALYs/outcome
33
Results: Incremental benefit of adding nirsevimab
on top of RSVpreF : By Month and Risk
$- $200,000 $400,000 $600,000 $800,000 $1,000,000 $1,200,000 $1,400,000 $1,600,000 $1,800,000ICER
1x 2x 3x 6x 10x
34Nirsevimab given in Oct -Mar
ICER= Incremental cost effectiveness ratio ($/QALY)
If the 10x bars are “missing”, providing nirsevimab is cost -saving.Birth Month
Risk LevelNirsevimab given at birth Nirsevimab given Oct/Nov
Results: Incremental benefit of adding nirsevimab
on top of RSVpreF : By Month and Risk
$- $50,000 $100,000 $150,000 $200,000 $250,000ICER
3x 6x 10x
35Nirsevimab given in Oct -Mar
ICER= Incremental cost effectiveness ratio ($/QALY)
If the 10x bars are “missing”, providing nirsevimab is cost -saving.Birth Month
Risk LevelNirsevimab given at birth Nirsevimab given Oct/Nov
Results: Adding nirsevimab to allinfants born year -
round to vaccinated mothers
- 200 400 600 800 1,000 1,200 1,400
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to
Avoid One…
1x 2x 3x 6x 10x
36Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through
September to mothers who received RSVpreF at least 2 weeks prior to delivery
Results: Adding nirsevimab to allinfants born year -
round to vaccinated mothers
37Notes: Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September to
mothers who received RSVpreF at least 2 weeks prior to delivery
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -year$413,035
$282,083
$192,782
$40,256
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
ICERICER
1x 2x 3x 6x 10xCost -Saving
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to deliveryResults: Adding nirsevimab at the start of the
season only for infants born Apr-Sept
- 200 400 600 800 1,000 1,200
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to
Avoid One…
1x 2x 3x 6x 10x
38
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to delivery
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearResults: Adding nirsevimab at the start of the
season only for infants born Apr-Sept
39$305,182
$203,194
$131,505
$4,830
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000ICER
1x 2x 3x 6x 10xCost -Saving
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to deliveryResults: Adding nirsevimab during the season for
infants born Oct-Mar
- 200 400 600 800 1,000 1,200 1,400 1,600
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to
Avoid One…
1x 2x 3x 6x 10x
40
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF at least 2 weeks prior to delivery
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearResults: Adding nirsevimab during the season for
infants born Oct-Mar
41$606,362
$416,695
$293,926
$95,537
$- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000ICER
1x 2x 3x 6x 10xCost -Saving
•Additional benefit beyond RSVpreF protection
•ICERs are high, but could be lower for higher -risk populations,
particularly if born off -peakSummary: Incremental benefit of
adding nirsevimab on top of RSVpreF
42
Incremental benefit of adding RSVpreF on top of
nirsevimab
•If you know the infant will be receiving nirsevimab
43
Results: Incremental benefit of adding RSVpreF on
top of nirsevimab
$2.4 $6.0 $9.4
$5.0
$3.6
$- $1.0 $2.0 $3.0 $4.0 $5.0 $6.0 $7.0 $8.0 $9.0 $10.0ICER (Millions)
44Birth Month
ICER= Incremental cost effectiveness ratio
Summary: Incremental benefit of adding RSVpreF
on top of nirsevimab
•Very marginal additional benefit beyond nirsevimab protection
•ICERs are extremely high
45
Overall summary: Combinations
•Limitation:
•No efficacy data for combination of products
•Nirsevimab may add additional protection on top of RSVpreF ,
particularly for higher -risk infants.
•Adding RSVpreF on top of nirsevimab adds marginal effectiveness at
very high cost in the general population
46
Thank You
•Please send comments to:
•[email protected]
47
Appendix to Economics of Pfizer maternal
RSVpreF vaccine
48
Research team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill, MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming -Dutra, MD, FAAP
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
•Andrew Leidner , PhD
49
Conflicts of interest statements
•Authors have no known conflict of interests.
50
Methods: Study question
•Determine the cost -effectiveness of RSVpreF by:
•Evaluating the population impact in terms of
•annual resource utilization
•total cases
•total costs
•deaths
•quality -adjusted life -years (QALYs)
•Comparing the incremental cost -effectiveness ratio (ICER) of RSVpreF to natural history/no
vaccine.
•Running scenario analyses outcomes that explore key areas of uncertainty.
•Perspective: Societal
51
Methods: Intervention(s)
•Target population: US pregnant persons
•Interventions:
1.No vaccination (Natural history)
2.RSVpreF against RSV illness
•Timeframe: 1 year (1 RSV season)
•Analytic horizon: infant’s lifetime
•Discount rate: 3%
52
Methods: Decision tree model
53Natural
History
RSVpreFInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsPrematurity
Injection site reaction
None of the aboveSerious adverse eventInfection Infection
Methods: Epidemiology
Hospitalization
54Base Case Range Source
Respiratory syncytial virus (RSV)
incidence, per 100,000 See Above See AboveCDC NVSN,
December 2016 to September 2020
Proportion with LRTI
Age 0 -5 months 1.0 0.5-1.0 Rainisch, 2020
Age 6 -11 months 1.0 0.5-1.0 Rainisch , 2020
CDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Sep tember 2020 - 1,000 2,000 3,000 4,000
0 2 4 6 8 10 12 14 16 18 20 22Hospitalization rate
per 100,000
children
Age in months
Methods: Epidemiology
ED and Outpatient
55Respiratory syncytial virus (RSV)
incidence, per 100,000 Base Case Range Source
Emergency Department
Age 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range), Hall
2009 (range)
Age 6 -11 months 5,800 5,700 –5,800 Lively 2019 (base case and range), Hall
2009 (range)
Age 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range), Lively
2019 (range)
Proportion with LRTI
Age 0 -5 months 0.65 0.25 -1.0 Rainisch , 2020
Age 6 -11 months 0.5 0.25 -1.0 Rainisch , 2020
Outpatient
Age 0 -5 months21,60013,200 –21,600 Lively 2019 (base case and range), Hall
2009 (range)
Age 6 -11 months24,60017,700 –24,600 Lively 2019 (base case and range), Hall
2009 (range)
Age 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and range),
Hall 2009 (range)
Proportion with LRTI
Age 0 -5 months 0.65 0.25 -1.0 Rainisch , 2020
Age 6 -11 months 0.3 0.1-1.0 Rainisch , 2020
LRTI= Lower respiratory tract infection
Methods: Epidemiology
Mortality
56Base
CaseRange Source
RSV mortality per
hospitalization
Age 0 -5 months 0.10%0.04 -0.20%Hansen 2022,
Doucette 2016
Age 6 -11 months 0.10%0.04 -0.20%Hansen 2022,
Doucette 2016
Age 12 -23 months 0.3% 0.28% -0.34% Gupta 2016
Seasonality
570%5%10%15%20%25%30%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)
Methods: Efficacy
58Variable Base case
valueRange for
sensitivity
analysisSource
RSVpreF
Initial efficacy (months 0 -5)
against medically -attended
RSV-associated LRTI 51.3% 29.4% -66.8%Kampmann
et al, 2023
Initial efficacy (months 0 -5)
against hospitalized RSV -
associated LRTI 56.8% 10.1% -80.7%Kampmann
et al, 2023
Efficacy months 6 -12 0
Assumed 0% efficacy against upper respiratory tract infections
LRTI= Lower respiratory tract infection
Methods: Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
Age 0 -11 months $11,487 4,804 -86,646
Bowser 2022Age 12 -23 months $11,469 4,804 -86,646
Disease -specific ED costs
(per ED visit)$563 544 -581 Bowser 2022
Disease -specific
outpatient costs (per
outpatient visit)$82 46 -118 Bowser 2022
59•Bowser, 2022 is a systematic review using studies from 2014 -2021
•Funded by Sanofi
•All numbers updated to 2022 dollars using GDP Deflator
Methods: Productivity costs
Variable Value Range Source
Productivity burden of RSV
disease (caregiver losses)
Days of lost productivity
Outpatient* 2.5 0-5Fragaszy, 2018; Petrie, 2016;
Van Wormer, 2017
ED* 2.5 0-5Fragaszy, 2018; Petrie, 2016;
Van Wormer, 2017
Hospitalization^ 7.4 0-14
Lifetime productivity for
those <1 year old (lost from
death)1,795,936 1,346,951 -
2,244,919Grosse, 2019
60*Productivity for outpatient and ED based on adult influenza
^Hospitalization productivity loss = length of hospitalization + 2 days
Methods: Intervention cost
Variable Value Range Source
Immunization -related costs
RSVpreF , per dose $295 50 –500Assumption: Manufacturer
costs for adult vaccine
RSVpreF administration $16.96 15 -22 Medicare: HCPCS 90460
61Both assume no additional visits, but do include costs of administration
Methods: Adverse event costs
Variable Value Range Source
RSVpreF Maternal Adverse
Events
Rate of injection site reaction 0.41 0.38 –0.44 Pfizer Phase 3 Trial
Probability of healthcare
visit, given injection site
reaction0.02 0.015 –0.025 Curran, 2020
Cost of outpatient visit $367.76 23.15 –1,758 (Deluca, 2023)
Recipient time, physician
office for injection site
reaction (hours)2 1 -3 Assumption
Hypothetical serious
adverse event0.000001 0 -0.0002Base: Prosser, 2006
High: 95% CI Phase 3 data for
RSV adult vaccines
62
63Kampmann B, Madhi SA, Munjal I, Simões EA, Pahud BA, Llapur C, Baker J, Pérez Marc G, Radley D, Shittu E, Glanternik J.
Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. New England Journal of Medicine. 2023 Apr 5.Methods: Prematurity?
1% Difference?
Methods: Prematurity scenario
Variable Value Range Source
RSVpreF infant adverse
events
Higher Rate of Prematurity 0% 0-2% Pfizer Phase 3 Trial
64 * All costs updated to 2022 using GDP DeflatorOutcomes, per prematurity
Lifetime cost of late
prematurity
Medical $ 23,241 $11,621 –
$46,482 Waitzman , Jalali, Grosse, 2021
Productivity $ 11,447 $5,724 –
$22,894 Waitzman , Jalali, Grosse, 2021
QALYs lost from late
prematurity0.03 0 –1.2Werner, Hauspurg , Rouse, 2015
Petrini et al, 2008, Hirvonen et al, 2014, Crump
et al, 2021, Darcy -Mahoney et al, 2016, Carroll
et al, 2009, Payakachat et al, 2014
Methods: RSV
health -related quality of life
65LRTI quality -adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)
Outpatient: Child 3.1 1.8 16.6
Outpatient: Caregiver 1.5 0 9.1
ED: Child 4.9 2.9 16.6
ED: Caregiver 2.5 0 9.1
Hospitalized: Child 6.2 3.7 26.5
Hospitalized: Caregiver 2.4 0 13.6Measured in
Days Lost
Most
Likely
Methods: Epidemiological model
SeasonalityIncidence
•Outpatient
•ED
•Hospitalizations
Nirsevimab
Waning
ProtectionHealth Effects
• Outpatient
• ED
• Hospitalizations
• Deaths
Economic Effects
• Intervention
• Disease
• Societal
• QALYs
• ICERInterventionsEpidemiology
Timing
Cost Burden/
•Outpatient
•ED
•HospitalizationsHealth Economics
Health Burden/
•Outpatient
•ED
•Hospitalizations
66
Methods: Inputs
•Incidence
•Raw reported incidence may be underreported because of imperfect PCR
sensitivity, so we consider an additional scenario in sensitivity analysis:
•based on CDC Unpublished re -analysis of raw data from Zhang et al study which found
decreased RSV PCR sensitivity in light of paired serology testing (adjustment factor:
87.6%).
67
Health -Related Quality -of-Life
•Sources
•Glaser (2022)
•Estimate based on comparison of utility losses between premature children who had RSV vs.
premature children without RSV and their caregivers
•Used as base case for hospitalization for children and their caregivers
•Regnier (2013)
•Estimate QALY losses for hospitalization, ED visits, and outpatient visits for children with
pertussis
•Use relative QALYs between hospitalization, ED, and outpatient to estimate base losses for ED
and outpatient in base case
•JIVE RSV Utilities Survey (2021)
•Estimates QALY losses for hospitalization and outpatient visits for child and caregiver
•Estimates may be impacted by COVID -related concerns about respiratory viruses
•Inform upper bound of range
68
69Timing of those who received vaccination during pregnancy
RSVpreF is assumed to start earlier at week 24 (vs. week 27)Methods: Provision of RSVpreF
00.050.10.150.20.25
1 3 5 7 911 13 15 17 19 21 23 25 27 29 31 33 35 37 39Fraction Vaccinated (given receipt
of vaccine)
Gestational Age
Reported Tdap Modeled RSVpreF vaccination timing
700.0%5.0%10.0%15.0%20.0%25.0%30.0%35.0%40.0%45.0%
0 10 20 30 40 50
Gestational Age (Week)
Source: NCHS from 2019 and 2021Methods: Birth Timing
Validation
231
66
8225
65
13
050100150200250
Outpatient Clinic
VisitsED Visits HospitalizationsRates of Medically -Attended RSV
(per 1000 births)
Rainisch et al, Vaccine, 2020 JIVE model
71
Methods: Maternal Adverse Event Health Effects
Variable Value Range Source
Adult Quality -Adjusted Life -
Years lost due to adverse events
Injection Site Reaction 0 Assumed
Serious Adverse Event 0.141 0.092 -0.199 Prosser, 2006
72
Results: Health outcomes
73Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group
URTI= upper respiratory tract infection; LRTI= lower respiratory tract infection - 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000
Natural
HistoryRSVpreF Natural
HistoryRSVpreF Natural
HistoryRSVpreF
Outpatient Emergency Department InpatientNumber of Events in Cohort
URTI LRTI
Results: Events Averted
74Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group45,693
15,866
7,571
1,66640,884
4,997
05,00010,00015,00020,00025,00030,00035,00040,00045,00050,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Year
RSVPreF
Results: QALYs Lost
75Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural
History 7,153 3,580 3,290 1,645 807 320 1,356 12,606 5,545 18,151
RSVpreF 0.2495 6,766 3,387 3,075 1,538 679 269 1,141 11,663 5,194 16,857
Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group
QALY= quality -adjusted life -year
76Sensitivity: Hospitalization Mortality
Base$0$50,000$100,000$150,000$200,000$250,000$300,000$350,000$400,000$450,000$500,000
0.00% 0.20% 0.40% 0.60% 0.80% 1.00% 1.20%ICER
Hospitalized Mortality
Scenario: Prematurity
77Base Case
$- $200,000 $400,000 $600,000 $800,000 $1,000,000 $1,200,000 $1,400,000 $1,600,000
0.0% 0.5% 1.0% 1.5% 2.0%ICER
Excess Prematurity
Scenario: Upper Respiratory Tract Infection Effect
78RSVpreF is assumed to have 37.9% efficacy for upper respiratory tract infections based on overall respiratory tract
efficacy from phase 3 trial ( Kampmann , 2023)
ICER= incremental cost effectiveness ratio; QALY= Quality adjusted life year$279,490/QALY
$- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000
$0 $50 $100 $150 $200 $250 $300 $350 $400 $450 $500ICER
Total Cost of RSVpreF
Appendix to Economics of combined use of Pfizer
maternal RSVpreF vaccine and nirsevimab
79
Methods: Study questions
•Determine the cost -effectiveness of:
•Nirsevimab in children born to mothers who received RSVpreF at least 2 weeks prior to
delivery
•RSVpreF for pregnant persons who will give nirsevimab to their newborns
•Single individual
•Evaluate by month of year
•Perspective: Societal
•Timeframe: 1 year (1 RSV season)
•Analytic horizon: infant’s lifetime
•Discount rate: 3%
80
810.0%5.0%10.0%15.0%20.0%25.0%30.0%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)Reminder: Seasonality
Methods: Intervention effectiveness
82* Assuming administration of nirsevimab at birth0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both Nirsevimab
0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both NirsevimabMethods: Intervention effectiveness
83
Additional benefit of adding RSVpreF
* Assuming administration of nirsevimab at birth
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Hospitalization Efficacy
Month
Both Nirsevimab OnlyMethods: Intervention effectiveness
example: Off -peak (Aug) birth
Additional benefit of adding RSVpreF
84
Results: Adding nirsevimab to allinfants born to
vaccinated mothers
0.00000.05000.10000.15000.20000.2500
Outpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per
Infant Given Nirsevimab
1x 2x 3x 6x 10x
85Nirsevimab given at birth for infants born October -March, and in October/November for infants born in April through
September
Results: Adding nirsevimab at the start of the
season only for infants born Apr-Sept
0.00000.05000.10000.15000.20000.25000.3000
Outpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per
Infant Given Nirsevimab
1x 2x 3x 6x 10x
86Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF
Results: Adding nirsevimab during the season for
infants born Oct-Mar
0.00000.05000.10000.15000.2000
Outpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per
Infant Given Nirsevimab
1x 2x 3x 6x 10x
87Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF