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 Mercon , MSCDC
•Michael Melgar , MD
•Mila Prill, MSPH
•Jamison Pike, PhD
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Christopher Taylor, PhD
•Amadea Britton, MD
2
Conflicts of interest statements
–No known conflict of interests.
3
Methods: Study question
•Determine the cost -effectiveness of RSV vaccination by:
•Evaluating the population burden of disease in the US
population
•Comparing vaccination to no vaccination using the incremental
cost-effectiveness ratio
•Scenario analyses exploring uncertainty.
•Perspective: Societal
•Major updates:
•Update to base case incidence of RSV
•Incorporation of season 2 efficacy of a single vaccine dose
•Alignment of vaccine price with that assumed by manufacturers
4
Methods: Intervention(s)
•Target population: US adults, stratified by age
•Interventions: Pfizer and GSK vaccines
•Each compared to No Vaccination
•Base case assumes the age -based RSV vaccination
recommendation is for ages ≥65
•Timeframe: 2 years
•Analytic horizon: lifetime
•Discounting rate: 3%
5
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
–Raw reported incidence may be underreported
because of imperfect PCR sensitivity
▪Base case assumption: 1.5x multiplier was applied to
crude incidence estimates
▪Lower bound: lower multiplier assuming 95% PCR
sensitivity (fewer missed cases)
▪Higher bound: upper bound from base case assumption
7For incidence of inpatient (RSV -NET), outpatient, and ED visits (McLaughlin et al. 2022), this applies the McLaughlin et al. mul tiplier of 1.5x to the crude
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.
Other studies speak directly to under -detection of RSV infection through use of upper respiratory PCR alone:
•Onwuchekwa C, Moreo LM, Menon S, Machado B, Curcio D, Kalina W, Atwell JE, Gessner BD, Siapka M, Agarwal N, Rubbrecht M. Under -ascertainment of Respiratory Syncytial
Virus infection in adults due to diagnostic testing limitations: A systematic literature review and meta -analysis. The Journal o f Infectious Diseases. 2023 Jan 20.
•Ramirez J, Carrico R, Wilde A, Junkins A, Furmanek S, Chandler T, Schulz P, Hubler R, Peyrani P, Liu Q, Trivedi S. Diagnosis of Respiratory Syncytial Virus in Adults Substantially
Increases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab RT –PCR. Infectious Diseases and Therapy. 2023 May 6:1 -1.
Methods: Epidemiology
Hospitalization
Variable Value Range Source
age 60 to <65 years 65.5 47.2 –101.3
CDC RSV -NETage 65 to <70 years 93.8 65.9 –149.1
age 70 to <75 years 118.7 85.5 –183.1
age ≥75 years 302.9 212.6 –489
•CDC RSV -NET data from RSV seasons: 2016 -17, 2017 -18, 2018 -19, and 2019 -2020.
•Base value is based upon the average burden adjusted rate over those four seasons where
“burden adjusted” means it is adjusted for 1.5x based on a reduced PCR test sensitivity *
•Range lower bound is based upon the average burden adjusted rate over those four seasons,
but it uses a different “burden adjustment” multiplier of a "Standard" PCR test sensitivity of
95%**.
•Range upper bound is based on the upper 95% confidence limit for the base estimates
* 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) -assoc iated 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.
** McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infe ct Dis. 2022 Jun 17;9(7):ofac300.
doi: 10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.8RSV incidence, per 100,000, Hospitalization
Methods: Epidemiology
ED and Outpatient
Variable Value Range Source
RSV incidence, per 100,000
Emergency Department
age 60 to <65 years 110.4 74 –132
McLaughlin 2022 age 65 to <74 years 200 133 –478
age ≥75 years 200 133 –478
RSV Incidence, per 100,000
Outpatient
age 60 to <65 years 1722 1148 –2041
McLaughlin 2022 age 65 to <74 years 2278 1519 –2893
age ≥75 years 2278 1519 –2893
9•McLaughlin et. al. is a Pfizer -sponsored meta -analysis
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: 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
10
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 810 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy
Month
Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Est. Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Against medically-attended RSV-associated ARI (outpatient)
Est. Against medically-attended RSV-associated ARI (outpatient)
11Efficacy of a single vaccine dose
over time: Pfizer
Linear decay to
0% by 24 months84.6%
65.2%75.0%
55.0%
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy
Month
Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Est. Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Against medically-attended RSV-associated ARI (outpatient)
Est. Against medically-attended RSV-associated ARI (outpatient)87.5%
52.9%79.0%
27.8%Linear decay to
0% by 24 months
12Efficacy of a single vaccine dose
over time: GSK
Upper and Lower Bound Efficacy
Duration Scenarios
13GSK Pfizer
0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended
RSV- LRTI/LRTD
(hospitalization and ED)
Base Shorter Longer0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended
RSV- LRTI/LRTD
(hospitalization and ED)
Base Shorter Longer
Methods: RSV Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
age 60 to <65 years $21,417 9,288 –45,454
Ackerson 2020* age 65 to <75 years $21,417 10,491 –43,619
age ≥75 years $22,425 10,491 –43,619
Disease -specific ED costs
(per ED visit)
age 60 to <65 years $1,210 -
2016 Marketscan* age 65 to <75 years $1,210 -
age ≥75 years $1,210 -
Disease -specific
outpatient costs (per
outpatient visit)
age 60 to <65 years $117.58 65.88 -145.38 MarketScan
and Medicare FFS, 2020 -
2021age 65 to <75 years $100.86 50.48 -120.08
age ≥75 years $100.86 50.48 -120.08
*Updated to Q3 2022$ using GDP Deflator14
Methods: Additional Inputs
•Also included
–RSV mortality
–RSV QALYs lost
–RSV illness productivity costs
–Vaccination healthcare and productivity costs
–Vaccination adverse events
•Systemic reactions
•Injection site reactions
•Serious adverse events
•Medical costs
•Productivity costs
•These assumption remain unchanged from
February
15
Methods: Sensitivity analyses
•Sensitivity analyses conducted
–One-Way and Two -Way
–Age-based recommendation for RSV vaccination
•age ≥65 years
•age 60 to <65 years
–Vaccine cost
▪$180 -$340
•Scenario analysis: shorter and longer duration of
efficacy
16
Results: Base Case
•Cohort of US adult population age 65+ as
of 2020 Census
•Vaccine Cost:
–Pfizer: $200
–GSK: $270
•Two Year Timeframe
17
Number Needed to Vaccinate,
Pfizer
18
Two Year Timeframe
52
617
1,040
5,201
26,671
173
1,734 40
340
401
2,007
7,842
67
669
- 5,000 10,000 15,000 20,000 25,000 30,000Number Needed to Vaccinate
Age 60-64 age ≥65 years
Net Cost per Outcome Averted,
Pfizer
19Two Year Timeframe
Age-based vaccination recommendation: ≥65 years
Pfizer vaccine cost: $200Outpatient ED Hospitalizations ICU Stays Deaths
≥65 years $5,600 $48,000 $57,000 $280,000 $1,100,000
60 to <65 $9,400 $110,000 $190,000 $930,000 $4,800,000
Number Needed to Vaccinate,
GSK
20Two Year Timeframe
57
669
1,128
5,639
28,919
188
1,880 43
369
435
2,176
8,503
73
725
- 5,000 10,000 15,000 20,000 25,000 30,000 35,000Number Needed to Vaccinate
age 60 to <65 years age ≥65 years
Net Cost per Outcome Averted,
GSK
21Two Year Timeframe
Age-based vaccination recommendation: ≥65 years
GSK vaccine cost: $270Outpatient ED Hospitalizations ICU Stays Deaths
≥65 years $9,300 $80,000 $94,000 $470,000 $1,800,000
60 to <65 $14,000 $170,000 $290,000 $1,400,000 $7,300,000
Summary measure(s)
Pfizer
Age-based vaccination
recommendation: ≥65 years ICER ($/QALY) ICER ($/LY)
94,673 112,806
22QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life -Year
ICER values do not depend on cohort size or uptake
$200 vaccine cost
Two Year Timeframe Age-based vaccination
recommendation: 60 to <65
years ICER ($/QALY) ICER ($/LY)
218,350 313,379
Summary measure(s)
GSK
Age-based vaccination
recommendation: ≥65 years ICER ($/QALY) ICER ($/LY)
167,301 187,853
23QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life -Year
ICER values do not depend on cohort size or uptake
$270 vaccine cost
Two Year Timeframe Age-based vaccination
recommendation: 60 to <65
years ICER ($/QALY) ICER ($/LY)
372,656 478,947
Results: Sensitivity analyses,
•Tornado Diagrams
–one parameter varied at a time
•Age and Vaccine Cost
•Vaccine Duration
24
Sensitivity analyses, Pfizer
Tornado Diagram
25$200 vaccine cost
Two Year Timeframe
Age-based vaccination recommendation: ≥65 years, VE=Vaccine Efficacy LRTD= Lower Respiratory
Tract Disease, S1=Season 1, S2=Season 2.$0 $50,000 $100,000 $150,000 $200,000
Vaccine Cost
VE against hospitalization and ED S2
Incidence of RSV hospitalization
VE against hospitalization and ED S1
Cost per Hospitalization
Outpatient QALYs Lost, Adult
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
VE against oupatient illness S2
ED IncidenceICERAge ≥65
Low Assumption High Assumption
Sensitivity analyses, GSK
Tornado Diagram
26$270vaccine cost
Two Year Timeframe
Age-based vaccination recommendation: ≥65 years, VE= Vaccine Efficacy, LRTD= Lower Respiratory
Tract Disease, S1=Season 1, S2=Season 2.$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000
Incidence of RSV hospitalization
VE against hospitalization and ED S2
Vaccine Cost
Outpatient QALYs Lost, Adult
Cost per Hospitalization
VE against hospitalization and ED S1
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
VE against oupatient illness S2
ED IncidenceICERAge ≥65
Low Assumption High Assumption
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
$150 $175 $200 $225 $250 $275 $300 $325 $350ICER
Vaccine Cost
Age 60-64 age ≥65 yearsSensitivity analysis: Vaccine
Cost, Pfizer
27Two Year Timeframe
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
$150 $175 $200 $225 $250 $275 $300 $325 $350ICER
Vaccine Cost
Age 60-64 age ≥65 yearsSensitivity analysis: Vaccine
Cost, GSK
28Two Year Timeframe
0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended RSV-
LRTI/LRTD (hospitalization and ED)
Base Shorter Longer0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended RSV-
LRTI/LRTD (hospitalization and ED)
Base Shorter LongerPfizer GSKVaccine Efficacy Duration
Scenarios
29
Sensitivity analyses, Pfizer:
Varying Duration of Efficacy
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
$150 $175 $200 $225 $250 $275 $300 $325 $350ICER
Vaccine Cost
Pfizer Base age ≥65 years
Pfizer Zero Efficacy after 14 months age ≥65 years
Pfizer Zero Efficacy after 36 months age ≥65 years
30Age-based vaccination recommendation: ≥65 years
Sensitivity analyses, GSK:
Varying Duration of Efficacy
$- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
$150 $175 $200 $225 $250 $275 $300 $325 $350ICER
Vaccine Cost
GSK Base age ≥65 years
GSK Zero Efficacy after 18 months age ≥65 years
GSK Zero Efficacy after 36 months age ≥65 years
31Age-based vaccination recommendation: ≥65 years
Limitations
•Model Structure
–No risk groups
–No dynamic transmission. No impact of the vaccine
on transmission and indirect effects
•Uncertain inputs
–Vaccine cost
–RSV Incidence
–Long -term efficacy
32
Summary
•Vaccination potentially Cost -Effective
•Results vary based on:
–Vaccine Cost
•ICER: 80,000 –220,000 $/QALY
–Incidence of RSV Hospitalization
•$50,000 -230,000 $/QALY
–Vaccine Efficacy
•ICER: ~80,000 -270,000 $/QALY
–Ages Vaccinated
•ICER: ~50,000 -370,000 $/QALY
–Duration of Efficacy
•ICER: ~80,000 -170,000 $/QALY33
Thank You
•Please send comments to:
•[email protected]
34