Document text
1
Cost -effectiveness of live attenuated chikungunya vaccine among adults
living in US territories
Kelly Kilburn, PhD, Martin I. Meltzer, PhD, Seonghye Jeon, PhD, Susan L. Hills, MBBS,
MTH, Bishwa B. Adhikari, PhD, Nicole P. Lindsey, MS, J. Erin Staples, MD, PhD
June 27th, 2024
National Center for Emerging Zoonotic and Infectious DiseasesNational Center for Emerging Zoonotic and Infectious Diseases
2•Authors have no known conflict of interests
•The findings and conclusions in this presentation are those of the authors and do
not necessarily represent the views of the Centers for Disease Control and Prevention.Conflicts of Interest Statement
3•Research question
•Methods
•Results
•Sensitivity analyses
•Limitations
•SummaryOutline
4•What is the cost -e ffectiveness of using a single dose of the live
attenuated chikungunya vaccine among the population aged ≥18 years
in US territories* that previously experienced an outbreak of chikungunya?
*American Samoa, Puerto Rico (PR), and US Virgin Islands (USVI)Research Question
5Methods
6•Population- based model
-Entire population of three US territories in model
•Time step: 1 year
•Analytic time horizon: 30 years starting in 2024
•Discount rate: 3%
•Perspectives: societal and healthcare payer
•One chikungunya outbreak occurring in 2034Economic Model
7•Use of live-attenuated chikungunya vaccine
Strategy 1:
Routine VaccinationStrategy 2:
Outbreak Vaccination
Annual Vaccination Yes No
Coverage rate1 20% --
Outbreak campaign in 2034 Yes Yes
Coverage rate2 70%3 70%
1 Routine coverage rate range based on annual influenza vaccine uptake in Puerto Rico (CDC data)
2 Outbreak coverage rate range based on Covid -19 vaccine uptake in Puerto Rico (CDC data)
3 Total coverage rate for outbreak year considers routine vaccinations from all prior years and vaccinations during outbreak. Individuals are vaccinated only once.Intervention
8Routine strategy
Initial vaccination
of target populationOutbreak vaccinationof target population
Vaccination of new 18 yo Vaccination of new 18 yo
Outbreak strategy
Outbreak vaccinationof target population2053
20532024
2024 20342034Strategy Comparison
9•Estimated population- level health outcomes
-Symptomatic cases
-Hospitalizations
-Chronic joint pain cases
-Deaths
-Quality -adjusted life -years (QALYs) lost
•Estimated economic outcomes
-Societal costs – vaccination, medical, and lost productivity costs
-Healthcare payer costs – vaccination and medical costsOutcomes
10•Calculated incremental cost -effectiveness ratios comparing
vaccination to no vaccination
-Measured as $ per each outcome averted (or QALYs gained)
•Monte Carlo simulation with 1,000 replications to estimate results
with 95% CIs using @Risk software
•Conducted sensitivity analyses (univariate and scenario)Analysis Approach
11Model Assumptions
12•Chikungunya virus infection confers lifetime immunity
•Outbreak would stop once certain level of population is infected
(halting seroprevalence)Lifelong Immunity and Halting Seroprevalence
13Model Inputs
14USVI – US Virgin Islands; PR – Puerto Rico
* Level of population immunity from prior outbreak in adult population. By 2024, baseline seroprevalence
has waned to 28% in population.Variable Value Range Source
Low High
Baseline seroprevalence* 31% 18% 42% USVI1 and PR2 data
% symptomatic among infected 72% 53% 97% USVI data1Infection Inputs
1. Hennessey MJ, et al. Amer J Trop Med Hyg , 2018; 99:1321- 1321.
2. Adams LE, et al. PLOS NTD. 2022; 16:e0010416- e0010416.
15Variable Value Range Source
Low High
% care -seeking 43% 30% 82% USVI data1
% hospitalized*10% 5% 15% USVI data1
% with chronic joint pain+35% 19% 61% Metanalysis2
% death^ 1% 0.1% 3% PR data3
USVI – US Virgin Islands, PR – Puerto Rico
* of those seeking care
+ 6 months after infection
^ of those hospitalized1Hennessey MJ, et al. Amer J Trop Med Hyg , 2018; 99:1321- 1321.;
Hennessey MJ, et al. Centers for Disease Control and Prevention, 2015.
2Lindsey NP. ACIP presentation. 2023
3Sharp TM, et al. J Infect Dis. 2016; 214: S475- S 481Health Outcome Inputs
16•Vaccine seroresponse rate of 96.3% (clinical trial data)1
•Decay in vaccine seroresponse rate of 5 percentage points every 5 years based on
other live attenuated or chimeric vaccines2
1.Schneider M, et al. Lancet. 2023; 401:2138- 2147.
2.Lindsey NP, et al. J Travel Medicine. 2018; 25:tay108; Desai KL, et al.
Vaccine. 2012; 30:2510- 2515.40%60%80%100%
2024 2034 2044 2054Seroresponse rateEstimated Vaccine Seroreponse Over Time HorizonVaccine Seroresponse
17Variable Time Weight
(range)QALYs Lost
(range)Source
Non -hospitalized case*^ 7 days0.63
(0.19- 0.91)0.01
(0.002- 0.016)Dengue1
Hospitalized case* 14 days0.56
(0.19- 0.91)0.02
(0.004- 0.031)Dengue1
Chronic joint pain case 1 year0.76
(0.65- 0.90)0.24
(0.10- 0.35)Chikungunya and
rheumatoid
arthritis2,3
QALY – quality -adjusted life -year; QALY losses due to death are included and include loss
beyond time horizon of model
*Weights for acute disease based on dengue; no weights available for chikungunya^All symptomatic cases had QALY losses regardless of care -seeking behavior QALY Inputs
1 Zeng W, et al. Am J Trop Med Hyg. 2018; 99:1458- 1465.
2 Couzigou B, et al. Am J Trop Med Hyg. 2018; 99:182- 190.
3 Sorensen J, et al. Value Health. 2012; 15:334- 339
18Sensitivity Analyses Methods
19•Univariate (one- way) analysis
-Varied one parameter at a time and calculated mean $/QALY gained using low (1%)
and high (99%) values of input distributions
•Scenario analyses
-Altered year of outbreak to 2029 or 2039 (base: 2034)
-Altered halting seroprevalence to 30%1 or 80%2 (base: 40%)
-Altered vaccination coverage
•Routine 10% or 30% (base: 20%)
•Outbreak 50% or 85% (base: 70%)
1 Hennessey MJ, et al. Amer J Trop Med Hyg, 2018; 99:1321- 1321 &
Adams LE, et al. PLOS NTD. 2022; 16:e0010416- e0010416
2 Jamaican MoH. JHLSIII, 2018Sensitivity Analyses
20Results
21•Outbreak strategy averts 67% of health outcomes
•Routine strategy averts 90% of health outcomes
040,00080,000120,000160,000200,000
Symptomatic Cases Hospitalizations Chronic joint pain Deaths QALYs lostNo vaccination Outbreak RoutineHeath Outcomes
22•More doses delivered in routine strategy during 30- year time horizon
than outbreak strategy
•Base scenario vaccination costs
•Routine strategy : $436 million
•Outbreak strategy : $356 million
*Vaccination costs include vaccines, administration, and adverse event costs
All costs converted to 2023 $USVaccination Doses and Costs*
23Outcome StrategyTotal costs,
No vaccine
(millions)Total costs,
Vaccine
(millions)Difference
Societal Costs*Routine $566 $496 -12%
Outbreak $566 $547 -3%
Healthcare
Payer Costs^Routine $269 $465 73%
Outbreak $269 $449 67%
All costs converted to 2023 $US
* Societal costs include vaccination costs, direct medical costs, and indirect costs due to lost productivity.
^ Healthcare payer costs include vaccination costs and direct medical costs.Total Costs
24Symptomatic
CaseHospitalizationChronic joint
pain caseDeath QALY gained
Mean cost per outcome averted [95% CI]
Routine
StrategyCost
savingsCost
savingsCost
savingsCost
savingsCost
savings
Outbreak StrategyCost
savings$2,315
[$1K, $4K]$5
[Cost savings,
$200]$373,054
[$173K, $573K]$59
[Cost savings,
$1K]Cost -effectiveness, Societal Perspective
25*Presented from societal perspectiveSensitivity Analyses Results*
26$ 0 $ 5,000 $ 10,000 $ 15,000 $ 20,000Baseline seroprevalence
Proportion symptomatic
Cost medical, chronic joint pain
Proportion hospitalized
Proportion sought care
Vaccine cost
Cost medical, acute case
Proportion chronic joint pain
Time with joint pain
Cost lost productivity, acute case
Cost per QALY gainedRoutine Strategy
Outbreak StrategyTop 10 influential inputs, ranked by impact to mean $/QALY gained
Results not visible where the range
was < $0/QALY gainedUnivariate Sensitivity Analysis, Routine Strategy
27Routine strategy Outbreak strategy
Mean $/QALY gained
[95% CI]
Outbreak occurs in 2029 Cost savings$3,829
[$3K, $4.6K]
Outbreak occurs in 2039 Cost savings Cost savings
*Base scenario had outbreak occurring in 2034Sensitivity Analysis for Outbreak Timing*
28•30% halting seroprevalence: all scenarios have net positive costs
-Low vaccination has the lowest cost per QALY gained
•40% halting seroprevalence (base value): high vaccination has net
costs, base and low vaccination result in cost savings
-Low vaccination has the lowest cost per QALY gained
•80% halting seroprevalence: all scenarios result in cost savings
-High vaccination has lowest cost per QALY gainedScenario Analysis Varying Halting Seroprevalence and
Vaccination Coverage*
*Vaccination Coverage Rates:
Base vaccination= 20% routine, 70% outbreak; Low vaccination= 10% routine, 50% outbreak; High vaccination= 30% routine, 85% o utbreak
29Limitations and Summary
301. No efficacy or effectiveness data available for current vaccine; data planned to be
generated in post- licensure studies
2.Limited evidence on outbreak frequency (i.e., when and how many) in same
geographical locations
3.QALY health utility weights mostly from dengue as proxy since no weights determined for acute chikungunyaLimitations
31•Chikungunya vaccine use in US territories would avert 67- 90% of cases and
associated health outcomes versus no vaccination
•Cost of intervention would range from $356 to $436 million depending on strategy
used
•Routine strategy had cost savings for each outcome while outbreak strategy had
mostly net positive costs in base scenario
•Results most affected by baseline and halting seroprevalenceSummary
32For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY: 1 -888- 232- 6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and
Prevention.