WSO - April 2023 - 422

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International Journal of Stroke 18(4)
Table 3. Health economic outcomes of LOF allele testing including life years and QALY gained (undiscounted).
Life expectancy, years
(undiscounted)
LOF allele testing
Standard of care
16.40
16.26
LYG (undiscounted)
0.14
Reference
QALY (undiscounted)
12.31
12.19
QALY gained
(undiscounted)
0.12
Reference
CAD: Canadian dollars; QALY: quality-adjusted life years; LOF: loss-of-function.
Table 4. Health economic outcomes of LOF allele testing including QALY gained (discounted), costs (discounted), and ICER.
QALY
LOF allele testing
Standard of care
(discounted)
10.61
10.51
QALY gained
(discounted)
0.1
Reference
Costs, CAD$
(discounted)
7760
7329
Incremental cost,
CAD$ (discounted)
432
Reference
4310
Reference
CAD: Canadian dollars; QALY: quality-adjusted life years; LOF: loss-of-function; ICER: incremental cost-effectiveness ratio.
Sensitivity analysis
The base-case analysis was performed probabilistically
with 10,000 Monte Carlo simulations, with the final outputs
representing the expected (mean) values. Betadistributions
were applied to all probabilities and utilities,
gamma-distributions to all costs, and log-normal distributions
for all odds ratios and HR. Distributions were estimated
using the parameters (e.g. mean and standard errors)
from the respective published source documentation.
A series of deterministic one-way sensitivity analysis was
completed on several variables including the cost of minor
stroke, prevalence of LOF allele carriers, proportion of
strokes in the non-testing arm, and proportion of ICH, which
are important drivers of clinical outcomes. A multi-way
probabilistic sensitivity analysis was performed to assess
overall uncertainty, and a cost-effectiveness acceptability
curve is reported to show the probability that a strategy is
cost-effective given certain willingness-to-pay thresholds.
All analyses were performed using the TreeAge Pro
Healthcare 2021 (TreeAge Software Inc., Williamstown, MA,
USA). The local institutional review board waived the need for
patient consent or ethics approval for this economic analysis.
Results
Clinical benefits
In the base-case analysis, LOF allele testing leads to 0.14
LYG or 0.12 QALYs gained (undiscounted) compared to
standard of care.
Economic evaluation
After discounting for the economic base-case analysis,
LOF allele testing leads to additional discounted lifetime
costs of CAD$432 per patient with corresponding 0.10
International Journal of Stroke, 18(4)
Discussion
We evaluated the long-term clinical effectiveness and costeffectiveness
of testing for CYP2C19 LOF allele status to
discounted QALYs gained, which results in a discounted
ICER of CAD$4310 per QALY for the LOF allele testing
strategy when compared with standard of care. Detailed
base-case figures are summarized in Tables 3 and 4.
Uncertainty assessment
Deterministic one-way sensitivity analyses were completed
on specific model parameters. First, if the cost of minor
stroke was set equal to the cost of a moderate stroke (i.e.
CAD$26,368), the ICER is CAD$9500 per QALY gained.
Second, if the LOF allele carrier prevalence was modeled at
a slightly increased 40% (with a standard error of 10%),
then the ICER slightly decreases (more cost-effective) to
CAD$3020 per QALY. Third, if the proportion of ischemic
stroke in the non-testing arm was modeling the same as the
non-carriers (6.7% rather than base-case value 7.6%), then
the ICER slightly increases to CAD$4790 per QALY.
Finally, we investigated the effect of ICH occurrence on
overall outcomes given the reduced prevalence in the aspirin-ticagrelor
group (2.0% vs 7.5%). If the proportion of
ICH in the aspirin-ticagrelor was modeled the same as the
aspirin-clopidogrel group (i.e. 7.5% of hemorrhages), the
ICER increases to CAD$10,400 per QALY still indicating
strong cost-effectiveness.
The probabilistic sensitivity analyses demonstrated that
LOF allele testing was cost-effective more than 99.99% of
simulations using a willingness-to-pay threshold of
CAD$50,000 per QALY (Figure 2). Even for an ICER threshold
of CAD$30,000 (20,000) per QALY, the probability of
LOF allele testing being cost-effective is 99.999% (99.1%).
ICER (CAD$/QALY)
(discounted)

WSO - April 2023

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