Document text
Economic Analysis of RSV
Vaccination in Older Adults
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 Michigan
Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Me rcon, MSCDC
•Michael Me lgar, MD
•Mila Prill , MSPH
•Jamison Pike, PhD
•Ismael Ortega - Sanchez, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Christopher Taylor, PhD
2
Conflicts of interest statements
–No known conflict of interests.
3
Methods: Study question
•Determine the cost -ef fectiveness of RSV vaccination by:
•Evaluating the population burden of disease in the US population
• ≥60 years old
• ≥65 years old
• ≥70 years old
• ≥75 years old
• Examining outcomes:
•resource utilization
•total cases
•total costs
•deaths
•quality -ad justed life years
•Comparing vaccination to no vaccination using the incremental cost -
ef
fectiveness ratio
•Scenario analyses exploring uncertainty.
•Perspective: Societal
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Methods: Intervention(s)
•Target population: US adults, stratified by age
•Interventions: GSK and Pfizer vaccines
•Each compared to No Vaccination
•Base case assumes the age - based RSV vaccination recommendation is
for ages ≥65
•Time horizon: 1 year
•Analytic horizon: lifetime
•Discounting rate: 3%
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Methods: Decision Tree Model
No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventInfection Infection
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Methods: Epidemiology
•Incidence of RSV
–
oRaw reported incidence may be underreported because of imperfect
PCR sensitivity
Base case assumption: 95% sensitivity
Additional scenario: lower sensitivity
Zhang et al study which found decreased RSV PCR sensitivity when paired serology
testing was added as an additional testing method.
7Zhang Y, Sakthivel SK, Bramley A, Jain S, Haynes A, Chappell JD, Hymas W, Lenny N, Patel A, Qi C, Ampofo K, Arnold SR, Self WH, Williams DJ, Hillyard D,
Anderson EJ, Grijalva CG, Zhu Y, Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Erdman DD. Serology Enhances Molecular Diagnosis of Respiratory Virus
Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia. J Clin Microbiol . 2016 Dec 28;55(1):79-89. doi:
10.1128/JCM.01701-16. PMID: 27795341; PMCID: PMC5228265
Methods: Epidemiology
Hospitalization
Variable Value Range Source
60≤ age ≤64 years 42 29 –103
CDC R SVnet 65≤ age ≤74 years 67 48 –203
age ≥75 years 193 133 –575
•CDC RSVnet data from RSV seasons: 2015- 16, 2016- 17, 2017- 18, and 2018- 19.
•Base value is based upon the average burden adjusted rate over those four seasons.
•“burden adjusted” means it is adjusted for a "Standard" PCR test sensitivity of 95%*.
•Range lower bound is based on the lower 95% confidence limit for the base estimates
•Range upper bound is based on the upper 95% confidence limit but also uses a different
“burden adjustment” multiplier of 1.4x based on a reduced PCR test sensitivity **
* Kujawski SA, Whitaker M, Ritchey MD, Reingold AL, Chai SJ, Anderson EJ, Openo KP , Monroe M, Ryan P , Bye E, Como -Sabetti K, Bar ney GR, Muse A, Bennett NM, Felsen
CB, Thomas A, Crawford C, Talbot HK, Schaffner W, Gerber SI, Langley GE, Kim L. Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with
congestive heart failure- United States, 2015 -2017. PLoS One. 2022 Mar 9;17(3):e0264890. doi: 10.1371/journal.pone.0264890. PMID: 35263382; PMCID: PMC8906631.
** Zhang Y , Sakthivel SK, Bramley A, Jain S, Haynes A, Chappell JD, Hymas W, Lenny N, Patel A, Qi C, Ampofo K, Arnold SR, Sel f WH, Williams DJ, Hillyard D, Anderson EJ,
Grijalva CG, Zhu Y , Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Erdman DD. Serology Enhances Molecular Diagnosis of Respir atory Virus Infections Other than
Influenza in Children and Adults Hospitalized with Community -Acquired Pneumonia. J Clin Microbiol. 2016 Dec 28;55(1):79- 89. doi: 10.1128/JCM.01701 -16. PMID:
27795341; PMCID: PMC5228265.8RSV incidence, per 100,000
Hospitalization
Methods: Epidemiology
ED and Outpatient
Variable Value Range Source
RSV incidence, per 100,000
Emergency Department
60≤ age ≤64 years 74 59 –132
McLaughlin 202265≤ age ≤74 years 133 0 –478
age ≥75 years 133 0 –478
RSV Incidence, per 100,000Outpatient
60≤ age ≤64 years 1148 935 –2041
McLaughlin 2022 65≤ age ≤74 years 1519 1109 –2893
age ≥75 years 1519 1109 –2893
9•McLaughlin et. al. is a Pfizer- sponsored meta -analysis
•Range upper bound is based on the upper 95% confidence limit but also uses the authors’
multiplier of 1.5x to adjust for PCR sensitivity
McLaughlin JM, Khan F, Begier E, Swerdlow DL, Jodar L, Falsey AR. Rates of Medically Attended RSV Among US Adults: A
Systematic Review and Meta- analysis. Open forum infectious diseases 2022 Jul (Vol. 9, No. 7, p. ofac300).
Methods: Inputs
Variable Value Range Source
RSV mortality per hospitalization
60≤ age ≤64 years 3.9% 3.12% –4.68%
CDC RSVnet 65≤ age ≤74 years 4.3% 3.44% –5.16%
age ≥75 years 5.7% 4.56% –6.84%
10CDC RSVnet data includes the following RSV seasons: 2015 -16, 2016- 17, 2017- 18, and 2018- 19.
Ranges incorporate a 20% increase/reduction from the base case value
Methods: Incidence
Seasonality
Source: NREVSS (2015 -19)0%5%10%15%20%25%30%
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepFraction of Annual Infections
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Methods: Efficacy
Variable Value Range Source
Vaccine Efficacy (%)
GSK
Medically attended RSV
LRTI/LRTD (ED, and
hospitalization)87.5% 58.4% –96.2% GSK phase 3 trial
Medically attended RSV ARI
(outpatient)79.0% 54.3% –91.5% GSK phase 3 trial
Pfizer
Medically attended RSV
LRTI/LRTD (ED, and
hospitalization)80.0% 6.3% –97.9% Pfizer phase 3 trial
Medically attended RSV ARI
(outpatient)69.2% 30.0% –88.0% Pfizer phase 3 trial
12
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Efficacy
Month
Against RSV-associated ARI (outpatient) Est. Against RSV-associated ARI (outpatient)
Against hospitalization and ED Est. Against hospitalization and EDEfficacy: GSK
average 6-month
efficacy = trial efficacy
Exponential decay
13
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Efficacy
Month
Against RSV-associated ARI (outpatient) Est. Against RSV-associated ARI (outpatient)
Against hospitalization and ED Est. Against hospitalization and EDEfficacy: Pfizer
average 6-month
efficacy = trial efficacy
Exponential decay
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Methods: RSV Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
60≤ age ≤64 years $20,330 9,288 –45,454
Ackerson 2020* 65≤ age ≤74 years $20,330 10,491 –43,619
age ≥75 years $21,339 10,491 –43,619
Disease -specific ED costs
(per ED visit)
60≤ age ≤64 years $1,210 -
2016 Marketscan* 65≤ age ≤74 years $1,210 -
age ≥75 years $1,210 -
Disease -specific
outpatient costs (per outpatient visit)
60≤ age ≤64 years $117.58 65.88-145.38 MarketScan
and Medicare FFS, 2020-
202165≤ age ≤74 years $100.86 50.48-120.08
age ≥75 years $100.86 50.48-120.08
*Updated to Q3 2022$ using GDP Deflator15
Methods: Vaccination-Related Costs
Variable Value Range Source
Vaccine, per dose $100 $50-$200 Assumption
Vaccine administration $16.96 -HCPCS 90460 (Physician Fee
Schedule 2022)
16And productivity costs for individuals time at clinic or pharmacy
Methods: RSV Health-Related Quality-of -Life
Variable Value Range Source
QALYs lost due to
Outpatient RSV 0.0185 0.0053- 0.0347 JIVE COVID/RSV
utilities study
(unpublished) Hospitalized RSV 0.0193 0.0095- 0.0316
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Methods: Additional Inputs
•Also included
–RSV illness productivity costs
–Vaccination productivity costs
–Vaccination adverse events
•Systemic reactions
•Injection site reactions
•Serious adverse events
•Medical costs
•Productivity costs
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Methods: Sensitivity analyses
•Sensitivity analyses conducted
–One-W ay and Two-Way
–Age- b ased recommendation for RSV vaccination
•age ≥60 years
•age ≥65 years
•age ≥70 years
•age ≥75 years
–Vaccine cost
$50-$200
•Scenario analysis: Higher incidence
19
Results: Base Case
•Cohort of 100,000
•20% vaccination coverage
•Age-bas ed vaccination recommendation: ≥65 years
•$100 vaccine cost
•One Year Time Horizon
20
Health Outcomes
21$100 vaccine cost
One Year Time HorizonCohort:100,000, 20% uptakeAge-based vaccination recommendation: ≥65 years1519
133108
22 6649
651280
111 90
18 5540
541308
11493
19 5555
56
02004006008001000120014001600
No Vaccination GSK Pfizer
Number Needed to Vaccinate, GSK
22One Year Time Horizon
90
1,032
1,348
6,740
27,284
225
2,247 84
893
1,097
5,486
21,442
183
1,829 84
893
895
4,475
16,691
149
1,492 84
893
615
3,076
10,794
103
1,025
- 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000Number Needed to Vaccinate
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Number Needed to Vaccinate, Pfizer
23
One Year Time Horizon
103
1,200
1,567
7,835
31,717
261
2,612 95
1,038
1,275
6,377
24,927
213
2,126 95
1,038
1,040
5,202
19,404
173
1,734 95
1,038
715
3,576
12,548
119
1,192
- 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000Number Needed to Vaccinate
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Cost per Outcome Averted
($ thousands)
24$100 vaccine cost
One Year Time HorizonAge-based vaccination recommendation: ≥65 years$8 $83 $101 $507 $1,982
$17 $169
$9 $100 $123 $614 $2,402
$20 $205
$- $500 $1,000 $1,500 $2,000 $2,500 $3,000Cost per Outcome Averted
ThousandsGSK Pfizer
Summary measure(s)
GSK
Costs (M) QALYs LostICER
($/QALY) LYs LostICER
($/LY)
No
Vaccination3.75 75 55
Vaccine 5.59 64 180,720 46 198,676
25QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life- Year
Cost, QALY, and LY Results per 100,000 (20% of whom are vaccinated)
Costs in Millions of 2022 dollarsICER values do not depend on cohort size or uptake$100 vaccine costOne Year Time Horizon Age-based vaccination recommendation: ≥65 years
Summary measure(s)
Pfizer
Costs (M) QALYs LostICER
($/QALY) LYs LostICER
($/LY)
No
Vaccination3.75 75 55
Vaccine 5.67 64 189,407 47 240,699
26QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life- Year
Cost, QALY, and LY Results per 100,000 (20% of whom are vaccinated)
Costs in Millions of 2022 dollarsICER values do not depend on cohort size or uptake$100 vaccine costOne Year Time Horizon Age-based vaccination recommendation: ≥65 years
Results: Sensitivity analyses,
•Tornado Diagrams
–one parameter varied at a time
•Age and Vaccine Cost
•Higher Incidence / Lower PCR Sensitivity
27
Sensitivity analyses, GSK Tornado Diagram
28$100 vaccine cost
One Year Time HorizonAge-based vaccination recommendation: ≥65 years$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
GSK Vaccine Effectiveness LRTD
Incidence of outpatient visits for RSV
Cost per Hospitalization
Mortality, adults hospitalized with RSV
GSK Vaccine Effectiveness ARI
ED Incidence
QALYs lost Injection Site ReactionICER ($/QALY)Age ≥65
Low Assumption High Assumption
Sensitivity analyses, Pfizer Tornado
Diagram
29$100 vaccine cost
One Year Time HorizonAge-based vaccination recommendation: ≥65 years
* A
t low Pfizer vaccine efficacy, the ICER rises to $574,730/QALY574,730$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
Pfizer Vaccine Effectiveness LRTD
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
Pfizer Vaccine Effectiveness ARI
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
Cost per Hospitalization
ED Incidence
Probability of Serious Adverse EventICER ($/QALY)Age ≥65
Low Assumption High Assumption
Sensitivity analysis: Vaccine Cost, GSK
30One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
$50 $75 $100 $125 $150 $175 $200ICER ($/QALY)
Vaccine Cost
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Sensitivity analysis: Vaccine Cost, Pfizer
31One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
$50 $75 $100 $125 $150 $175 $200ICER ($/QALY)
Vaccine Cost
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Sensitivity analyses, Higher Incidence
32•Higher incidence in the next 2 slides
assumes that RT -PCR test sensitivity is
lower than 95% and that additional RSV testing modalities would detect more cases at every level of care
1,2
1For incidence of hospitalization (RSV -NET), in lieu of adjusting observed incidence for RT -PCR sensitivity of 95%, a
1.4x multiplier is implemented based on Zhang et al. 2016 .
Zhang Y, et al. Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Ad ults Hospitalized with
Community -Acquired Pneumonia. J Clin Microbiol . 2016 Dec 28;55(1):79 -89. doi: 10.1128/JCM.01701- 16. PMID: 27795341; PMCID: PMC5228265.
2For incidence of outpatient and ED visits (McLaughlin et al. 2022), this applies the authors’ multiplier of 1.5x to the
lower (base case) incidence estimates.
McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infect Dis. 2022 Jun
17;9(7):ofac300. doi: 10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.
Sensitivity analyses, GSK
Higher Incidence
33Age-based vaccination recommendation: ≥65 years
One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
$
50 $75 $100 $125 $150 $175 $200ICER ($/QALY)
Vaccine Cost
GSK Base age ≥65 years GSK Higher Incidence age ≥65 years
Sensitivity analyses, Pfizer Higher Incidence
34Age-based vaccination recommendation: ≥65 years
One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
$50 $75 $100 $125 $150 $175 $200ICER ($/QALY)
Vaccine Cost
Pfizer Base age ≥65 years Pfizer Higher Incidence age ≥65 years
Limitations
•Model Structure
–No risk groups
–No dynamic transmission. No impact of the vaccine on transmission and
in
direct effects
–No direct medical costs post-di scharge (e.g. rehab)
•Uncertain inputs
–Vaccine cost
–RSV Incidence
–Long-t erm efficacy
35
Summary
•Results vary based on:
–Vaccine Cost
•ICER: ~80,000 -3 85,000 $/QALY
–Vaccine Efficacy
•ICER: ~150,000 -5 75,000 $/QALY
–Ages Vaccinated
•ICER: ~100,000 -2 30,000 $/QALY
–Incidence of Hospitalization
•ICER: ~30,000 -2 50,000 $/QALY
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Thank You
•Please send comments to:
•[email protected]
37