Document text
Economics of Pfizer maternal
RSVpreF vaccine
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 MichiganPresentation to the ACIP
June 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
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
4
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%
5
Methods: Decision tree model
6Natural
History
RSVpreFInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsPrematurity
Injection site reaction
None of the aboveSerious adverse eventInfection Infection
Methods: Epidemiology
Hospitalization
7Base 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
0246810121416182022Hospitalization
rate per 100,000
children
Age in months
Methods: Epidemiology
ED and Outpatient
8Respiratory syncytial virus
(RSV) incidence, per 100,000 Base
CaseRange 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 –
21,600Lively 2019 (base case and range),
Hall 2009 (range)
Age 6 -11 months24,60017,700 –
24,600Lively 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
9Base
CaseRange Source
RSV mortality per
hospitalization
Age 0 -5 months 0.04% 0.03-0.05% Doucette 2016
Age 6 -11 months 0.04% 0.03-0.05% Doucette 2016
Age 12 -23 months 0.3% 0.28% -
0.34%Gupta 2016
Seasonality
100%5%10%15%20%25%30%
Apr May Jun JulAug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)
110%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI
Against hospitalizationMethods: RSVpreF efficacy
average 6 -month efficacy
= trial efficacy
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
12Methods: RSVpreF efficacy
alternate scenario
average 6 -month efficacy
= trial efficacy
Zero efficacy
Source: Kampmann et al 2023
LRTI= Lower respiratory tract infection
Methods: Efficacy
13Variable 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: Provision of RSVpreF
14•Base case:
–Year round
•Scenarios
–During June -February (no vaccine given in
March -May)
–During May -February (no vaccine given in
March -April)
–During April -February (no vaccine given in
March)
•Mother vaccinated
–During 24 -36 weeks gestation, based on
distribution of Tdap vaccination by week in
that time period
•Birth
–Must be >2 weeks after vaccination for
protective efficacy to pass to infant, based on
historical gestational age
15 TDAP vaccination timing from internal CDC analysis of 2018 -2021 MarketScan data.Methods: Provision of RSVpreF
16100
Pregnant
persons50
Not
vaccinated
50
Vaccinated
47
Vaccinated
in time3
Not
vaccinated
in timeMethods: Provision of RSVpreF
Uptake
Timing
Timing= >2 weeks prior to delivery
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
17•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
18*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 $200 50 –300Assumption: Manufacturer
costs for adult vaccine
RSVpreF administration $16.96 15 -22 Medicare: HCPCS 90460
19Both 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
reaction0.41 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
20
21Kampmann 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
22* 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
23LRTI 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: Uncertainty analyses
•One-way sensitivity
•Scenarios:
–Prematurity
–Cost
–Month of administration
–Upper respiratory tract infection effect
–Efficacy waning
24
Results: Base case
25•Base case:
–Population of 1,000 births
–50% uptake in the RSVpreF group
–First RSV season
–$200/dose
–RSVpreF only impacts LRTI
Results: Health outcomes
26 Cohort:1,000 births, assuming 50% uptake in RSVpreF group
URTI= upper respiratory tract infection; LRTI= lower respiratory tract infection - 50 100 150 200 250
Natural
HistoryRSVpreF Natural
HistoryRSVpreF Natural
HistoryRSVpreF
Outpatient Emergency
DepartmentInpatientNumber of Events in Cohort
URTI LRTI
Results: Events Averted
27 Cohort:1,000 births, assuming 50% uptake in RSVpreF group12.9
4.5
2.1
0.511.6
1.4
0.02.04.06.08.010.012.014.0
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births
RSVPreF
Results: Number Needed to
Vaccinate
28 Cohort:1,000 births, assuming 50% uptake in RSVpreF group39 112 234 1,062
43 354
- 200 400 600 800 1,000 1,200
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Vaccinate to avoid
RSVPreF
Results: Costs
29
Base costs of RSVpreF : $200/dose, both natural history and RSVPreF involve palivizumab for high -risk childrenCohort:1,000 births, assuming 50% uptake in RSVpreF group$0$100,000$200,000$300,000$400,000$500,000$600,000
Natural History
RSVPreF
Natural History
RSVPreF
Natural History
RSVPreF
Natural History
RSVPreF
Natural History
RSVPreF
Natural History
RSVPreF
Intervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort
Medical Productivity
Results: Cost per Event Averted
30
Base costs of RSVpreF : $200/dose$5,459 $15,722 $32,945 $149,751
$6,101 $49,917
$- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000 $160,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
RSVPreF
Results: QALYs Lost
31Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural
History 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73
RSVpreF 0.0001 1.85 0.93 0.84 0.42 0.19 0.07 0.12 3.00 1.42 4.42
Cohort:1,000 births, assuming 50% uptake in RSVpreF group
QALY= quality -adjusted life -year
Results: Cost -Effectiveness
32Base costs of RSVpreF : $200/dose
QALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort:1,000 births, assuming 50% uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($)QALYs
lostICER ($/QALY)
Vs. NH
Natural History 418,556 4.73
RSVpreF 489,038 4.40 214,087
Sensitivity: Tornado RSVpreF
33Base cost of RSVpreF : $200/dose
MA= Medically -attended
LRTI= Lower respiratory tract infection
QALY= Quality adjusted life year$14 million$0 $100,000 $200,000 $300,000 $400,000 $500,000
Probability of Prematurity
Disease-specific inpatient costs (per inpatient case) Age 0-5
months
RSV QALYS Lost
RSVpreF vaccine cost/dose
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
RSV-related QALYs lost Outpatient Child
RSV-related QALYs lost Outpatient Caregiver
Proportion of RSV infections with an LRTI diagnosis ED Visits Age
0-5 monthsIncremental Cost -Effectiveness Ratio
Low High
$- $500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000 $3,000,000 $3,500,000 $4,000,000 $4,500,000 $5,000,000
0.0% 0.5% 1.0% 1.5% 2.0%ICER
Excess PrematurityScenario: Prematurity
34Base Case
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
$0 $50 $100 $150 $200 $250 $300ICER
Cost of RSVpreFSensitivity: Cost RSVpreF
35Base Case
Results: RSVpreF timing
scenarios
36•Scenarios
–Base: vaccine given year -round
–During April -February (no vaccine given in
March)
–During May -February (no vaccine given in
March -April)
–During June -February (no vaccine given in
March -May)
Results: RSVpreF timing
scenarios
214,087
162,136
137,871
119,398
- 50,000 100,000 150,000 200,000 250,000
Base Apr-Feb May-Feb Jun-FebICER ($/QALY)ICER: RSVpreF vs. Natural History
37
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
$0 $50 $100 $150 $200 $250 $300ICER
Total Cost of RSVpreFScenario: Upper Respiratory
Tract Infection Effect
38RSVpreF 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$153,674/QALY
39Methods: RSVpreF efficacy
“flat efficacy” scenario
OverallCosts ($)QALYs
lostICER ($/QALY)
Natural History 418,556 4.73
RSVpreF 486,812 4.38 191,749
Slightly lower costs with
RSVpreF , slightly fewer
QALYs lost, slightly lower
ICER0%20%40%60%80%100%
0 3 6 9 12Efficacy
Month
Against medically-attended RSV-associated LRTI
Against hospitalization
ICER: Incremental cost -effectiveness ratio
LRTI= Lower respiratory tract infection
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
40
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 (Cost -Saving –350,000 $/QALY)
–Efficacy (~150,000 -350,000 $/QALY)
–QALYs lost (~50,000 -480,000 $/QALY)
•Hospitalization, Outpatient, ED
•Child, Parent
–Month of Administration (~120,000 –215,000 $/QALY)
41QALY: Quality -Adjusted Life -Year
Thank You
•Please send comments to:
•[email protected]
42
Appendix
43
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
44
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%).
45
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
46
47 Timing of those who received vaccination during pregnancy
RSVpreF is assumed to start earlier at week 24 (vs. week 27)00.020.040.060.080.10.120.140.160.18
13579111315171921232527293133353739Fraction Vaccinated (given
receipt of vaccine)
Gestational Age
Reported Tdap Modeled RSVpreF vaccination timingMethods: Provision of RSVpreF
480.0%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
49
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
50
Results: Cost -Effectiveness
51
Base costs of RSVpreF : $200/doseCohort:1,000 births, assuming 50% uptake in RSVpreF group $410,000 $420,000 $430,000 $440,000 $450,000 $460,000 $470,000 $480,000 $490,000 $500,000
(4.80) (4.70) (4.60) (4.50) (4.40) (4.30)Costs
QALYs (lost) from RSV
Natural History RSVPreF
Results: RSVpreF Administration
June -February
52OverallCosts ($) QALYsICER
($/QALY)
Vs. NH
Natural
History 418,556 4.73
RSVpreF 454,928 4.43 119,398