Document text
Economic Analysis of
Nirsevimab in Pediatric
Populations
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 MichiganACIP General Meeting
February 23, 2023
Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Me rcon, MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill , MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming-Dutra
•Ismael Ortega - Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
7
Conflicts of interest statements
–Authors have no known conflict of interests.
8
Methods: Study question
•Determine the cost- ef fectiveness of nirsevimab by:
•Evaluating the population burden of disease in pediatric US
popul
ation in terms of
•annual resource utilization
•total cases
•total costs
•deaths
•quality- adj usted life years
•Comparing the incremental cost -ef fectiveness ratio of nirsevimab to
no prevention.
•Running scenario analyses outcomes that explore key areas of
unc
ertainty.
•Perspective: Societal
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Methods: Intervention(s)
•Target population: US pediatric < 7 months of age entering their
f
irst RSV season
•Secondary analysis high-r isk infants in their second RSV season (7 -18
months old)
•Interventions:
1.No n irsevimab (Natural history)
2.Nirsevimab against RSV illness
•Time horizon: 1 RSV season
•Analytic horizon: lifetime
•Discount rate: 3%
10
Methods: Decision Tree Model
11No
Prophylaxis
NirsevimabInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventInfection Infection
Methods: Epidemiology
Hospitalization
12Base 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 Septem ber 2020 - 1,000 2,000 3,000 4,000
0246810121416182022Hospitalization
rate per 100,000
children
Age in months
Methods: Epidemiology
ED and Outpatient
13Respiratory 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)
5,
Hall 2009 (range)6
Age 6 -11 months 5,800 5,700 –5,800
Age 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range)6,
Lively 2019 (range)5
Proportion with LRTI
Age 0 -5 months 0.65 0.25- 1.0 Rainisch, 20204
Age 6 -11 months 0.5 0.25- 1.0 Rainisch, 20204
Medically attended outpatient
Age 0 -5 months21,60013,200 –
21,600Lively 2019 (base case and range)
5,
Hall 2009 (range)6
Age 6 -11 months24,60017,700 –
24,600
Age 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and
range)7, Hall 2009 (range)6
Proportion with LRTI
Age 0 -5 months 0.65 0.25- 1.0 Rainisch, 20204
Age 6 -11 months 0.3 0.1-1.0 Rainisch, 20204
Methods: Epidemiology
Mortality
14Base
CaseRange Source
RSV mortality per hospitalization
Age 0-5 months 0.04% 0.03-0.05% Doucette 2016
8
Age 6-11 months 0.04% 0.03-0.05%
Age 12 -23 months 0.3% 0.24% -
0.28%Gupta 201610
Seasonality
150.0%5.0%10.0%15.0%20.0%25.0%30.0%
AprMay Jun JulAug Sep OctNov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015- 2019)
0.00%10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%90.00%100.00%
0 2 4 6 8 10 12 14Efficacy
MonthMethods: Inputs
average 5-month efficacy
= trial efficacy
Sigmoid decay to
final efficacy
16Zero efficacy
Methods: Efficacy
17Variable Base
case
valueRange for
sensitivity
analysisSource
Nirsevimab
Initial efficacy
(months 1- 5) against
RSV-associated
LRTI 80.0% 68.5% -86.1%MELODY trial
and Phase 2b recommended dose
Efficacy months 6-
10 25.0% 0.0% -50.0%
Efficacy after 10 months
0.0%
Methods: Provision of Nirsevimab
•Base case:
–At birth for those born
•October 1 – M arch 31
–October for those born in
•April (~6 -m onth visit)
•June (~4- m onth visit)
•August (~2- m onth visit)
–November for those born in
•May (~6 -m onth visit)
•July (~4- m onth visit)
•September (~2- m onth visit)
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Methods: Medical Costs
Variable Value Range Source
Disease-specific
hospitalization costs
(per hospitalization)
Age 0-11 months $11,487 11042 -11933
Bowser 2022Age 12- 23 months $11,469 11029 -11910
Disease-specific ED
costs (per ED visit)$563 544 –581 Bowser 2022
Disease-specific outpatient costs (per
outpatient visit)$82 46-118 Bowser 2022
19•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 Grosse, 2019
20*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
Nirsevimab, per dose $300 $50-$600 Assumption
21
Methods: RSV
Health-Related Quality-of -Life
22LRTI 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: Additional Inputs
•Also included nirs evimab adverse events
–Systemic reactions
–Injection site reactions
–Serious adverse events
–Medical costs
–Productivity costs
–Quality-adjust ed life- years lost
23
Methods: Uncertainty analyses
•One- w ay sensitivity
•Scenarios:
–Upper respiratory infection effect
–Timing of administration
•Additional Scenario:
–High-ri sk children entering the second RSV season
24
Results: Base Case
25•Base Case:
–Population of 1,000 births
–100% uptake in the nirsevimab group
–First RSV season
–$300/dose
–Nirsevimab only impacts LRTI
Results: Health Outcomes
26
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group231
172
67 46
13 5 - 50 100 150 200 250
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Medically attended
outpatientEmergency
DepartmentInpatient
URTI LRTI
Results: Health Outcomes
27
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group59
20.9
7.8
1.7 42.3
5.2
010203040506070
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births
Results: Health Outcomes
28
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group17 48 128 581
24 194
- 100 200 300 400 500 600 700
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid
Results: Costs
29
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Intervention Outpatient ED Inpatient Deaths Total
Medical Productivity
Results: Health Outcomes
30
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group$2,476 $6,950 $18,515 $84,158
$3,429 $28,053
$- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
Results: QALYs Lost
31Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural
History 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73
Nirsevimab 0.03 1.46 0.73 0.62 0.31 0.09 0.03 0.06 2.25 1.07 3.32
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Results: Cost-Effectiveness
32Overall Costs QALYsICER
($/QALY)
Natural
History $ 357,151 4.73
Nirsevimab $ 502,077 3.32 $ 102,805
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Sensitivity: Tornado
33
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group Cost QALYs Efficacy$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
Nirsevimab cost/dose
Initial Efficacy
Proportion of Outpatient visits (age 0-5 months) with an LRTI
diagnosis
Proportion of hospitalizations (age 0-5 months) with an LRTI
diagnosis
Proportion of ED Visits (age 0-5 months) with an LRTI
diagnosis
Proportion of outpatient visits (age 6-11 months) with an LRTI
diagnosis
RSV child QALYs lost due to outpatient visit
RSV caregiver QALYs lost due to outpatient visit
RSV child QALYs lost due to ED visit
RSV caregiver QALYs lost due to ED visitIncremental Cost-Effectiveness Ratio ($/QALY)
Low High
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
$0 $100 $200 $300 $400 $500 $600ICER ($/QALY)
Total Cost of Nirsevimab (drug + administration)Sensitivity: Cost
34 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Scenario: Upper Respiratory Infection Effect
35Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group57
20.4
7.7
1.741.4
5.1108
33.5
7.7
1.741.4
5.1
020406080100120
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 birthsEvents Averted
Averted Base Averted URTIOnly Outpatient and ED
are impacted by upper respiratory impact
$- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000
$0 $100 $200 $300 $400 $500 $600ICER ($/QALY)
Total Cost of Nirsevimab (drug + administration)Scenario: Upper Respiratory Infection Effect
36 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Nirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.
Scenario: Timing Analysis
37•Cost-effectiveness of an infant receiving nirsevimab as a
newborn in
– Oct- Feb
– Oct- March
– Oct- April
•With varying efficacy in months 6- 10
–0%
–25%
–50%
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
38Scenario: Timing and Efficacy in
months 6 -10
Slightly Lower ICERs for Oct -MarBase cost of $300/doseCohort:1,000 nirsevimab and 1,000
natural history, assuming 100% uptake in nirsevimab group $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000
0% efficacy 25% efficacy 50% efficacyICER ($/QALY)
Oct-Feb Oct-Mar Oct-Apr
Scenario: Reduction in Palivizumab
39Overall Costs QALYsICER
($/QALY)
Natural
History $ 418,551 4.73
Nirsevimab $ 502,077 3.32 $ 59,250
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group•Potential cost impact if clinicians choose to use n irsevimab in
palivizumab -eligible infants
•Savings assumptions:
–1.6% are high-risk (palivizumab-eligible)
–75% uptake in high-risk
–4.1 palivizumab doses/person on average
–$1,228/palivizumab dose
Higher -risk children entering the second
RSV season
40•Immunization in October (under 19 months old in
October)
•Incidence of RSV -associated hospitalization and mortality
per hospitalization:
–1x, 2x, 4x 6x, 10x higher
•Cost
–$600 nirsevimab costs (2x $300/dose)
–$1000 nirsevimab costs (2x $500/dose)
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Second Season, High -Risk
41
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group020406080100
Inpatient ICU Inpatient Days ICU DaysEvents Averted per 1000
ChildrenEvents Averted
Base 2x 4x 6x 10x
Second Season, High -Risk
42
Cost is per overall course, for 2 dosesCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab groupICER by cost of nirsevimab
(product plus administration) ($/QALY)
Hospitalization and
Mortality rate$600 $1000
1x (base) $ 815,051 $ 1,410,155
2x $ 449,238 $ 800,666
4x $ 145,014 $ 282,945
6x $ 53,061 $ 122,409
10x $ 404 $ 27,390
Limitations
•Model Structure
–No risk groups
–No dynamic transmission. No impact of the vaccine on transmission and
in
direct effects
•Uncertain inputs
–Nirsevimab co st
–QALYs lost
–Upper respiratory tract infections
–Palivizumab utilization
43
Summary
•Nirsevimab m ay be cost -effective
•Results sensitive to:
–Cost per dose (Cost -S aving –316,000 $/QALY)
–Efficacy (75,000 -153,000 $/QA LY)
•URTI/LRTI
–Proportion of infections with LRTI
–Or efficacy of ni rsevimab against URTI
–QALYs lost (41,000 -125,000 $/QA LY)
•Hospitalization, Outpatient, ED
•Child, Parent
44URTI: Upper Respiratory Tract Infection
LRTI: Lower Respiratory Tract InfectionQALY: Quality -Adjusted Life -Year
Thank You
•Please send comments to:
•[email protected]
45