1 A Cost-Effectiveness Analysis of Multi-Gene Pharmacogenetic Testing in Acute Coronary Syndrome Patients Following Percutaneous Coronary Intervention Olivia Dong, MPH Wiltshire Lab, Eshelman School of Pharmacy University of North Carolina at Chapel Hill, USA ISPOR 21 th Annual European Congress November 13, 2018 PGx is the study of genetic differences in drug metabolic pathways that can affect individual responses to drugs (therapeutic effect and/or adverse effects). Pharmacogenetics (PGx) Can Help Optimize Drug Prescribing
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Pharmacogenetics (PGx) Can Help Optimize Drug Prescribing
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A Cost-Effectiveness Analysis of Multi-Gene Pharmacogenetic Testing in Acute Coronary Syndrome Patients Following Percutaneous
Coronary Intervention Olivia Dong, MPH
Wiltshire Lab, Eshelman School of Pharmacy
University of North Carolina at Chapel Hill, USA
ISPOR 21th Annual European Congress
November 13, 2018
PGx is the study of genetic differences in drug metabolic pathways that can affect individual responses to drugs (therapeutic effect and/or adverse effects).
Pharmacogenetics (PGx) Can Help Optimize
Drug Prescribing
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Many Drugs Have PGx Guidelines
133 FDA-approved drugs have PGx information.
This includes information for 37 genes (germline
mutations).
36 drugs have CPIC guidelines.
This includes information for 14 genes (germline
mutations).
• These drugs cover various therapeutic areas: oncology, psychiatry, cardiology, infectious disease, etc.
• Only 7% of US hospitals offer PGx testing.
Johnson and Weitzel, Clin Pharmacol Ther., 2016
When patients are prescribed a drug with actionable
PGx guidance, should multi-gene or single gene PGx
testing be done?
Multi-Gene Testing
Provides genetic information to help optimize the
prescribing of an immediate drug PLUS additional
genetic information for drugs that may be prescribed
in the future.
Provides genetic information to help optimize
the prescribing of an immediate drug.
Single-Gene Testing
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ObjectiveTo determine the cost-effectiveness of multi-gene PGx testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) for acute coronary syndrome patients (ACS) undergoing percutaneous coronary intervention (PCI) compared to single-gene PGx testing (CYP2C19) and standard of care (no genotyping) from the perspective of Medicare.
Medication Gene(s) At-risk
genotype
Outcome Recommended action for
at-risk genotype carriers
Clopidogrel CYP2C19 *2-*8 Increased risk
for adverse
cardiovascular
events
Alternative antiplatelet is
recommended (prasugrel
or ticagrelor)1
Simvastatin SLCO1B1 rs4149056
TC or CC
Increased
myopathy risk
Prescribe lower dose or
consider alternative statin2
Warfarin CYP2C9
&
VKORC1
Various
combinations
Increased risk
for bleeding
A lower dose of warfarin is
recommended3
CVD medications with CPIC guideline recommendations
1Scott et al., Clin Pharmacol Ther., 2013 ; 2Ramsey et al., Clin Pharmacol Ther., 2014 ; 3Johnson et al., Clin Pharmacol Ther., 2017
The health benefits of multi-gene PGx testing have not been investigated in ACS patients undergoing PCI before.
Novelty
Multi-gene
Testing+
Medicare patients with
ACS undergoing PCI
health
benefits?=
4
CVD Patient Population
• ~300,000 PCI with stent placement are completed each year in Medicare patients with acute coronary syndrome (ACS).1
1Kim et al., Am J Cardiol., 20142Levine et al., J. Am. Coll. Cardiol., 20163Levine et al., Circulation, 20114Brilakis et al., JAMA, 20135Stone et al., J. Am. Coll. Cardiol, 2014
• A long-term statin is indicated as a secondary prevention measure.5
• Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is indicated for at least 12 months following a percutaneous coronary intervention (PCI) for ACS events.2-4
• A proportion of these patients may develop atrial fibrillation and require anticoagulation.
Basic Structure of the Model
Standard of Care
(no genetic testing)
Multi-Gene Testing
(CYP2C19, SLCO1B1,
CYP2C9, VKORC1)
Cost
QALYs
Cost
QALYs
Single-Gene Testing
(CYP2C19)
Cost
QALYs300,000 65-year
old Medicare
beneficiaries with
ACS undergoing
PCI
• Primary Outcome: Cost per quality-adjusted life years (QALY) gained
• Costs include genotyping, outcome events, and prescription costs
• QALYs reflect specific health outcomes that were tracked in the model
Outcomes:
Simulated model
cohort assigned to
each intervention:
Interventions:
• A hybrid decision tree/Markov model evaluated the lifetime costs and health benefits for the 3 intervention strategies.
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Timeline of Major Outcomes Tracked in Model
300,000 65-year
old Medicare
beneficiaries with
ACS undergoing
a PCI receive an
antiplatelet and
statin therapy
Evaluation for
atrial
fibrillation
(only those
prescribed
warfarin are
followed)
End
of
LifeWarfarin therapy
associated
outcomes: major
bleed,
thromboembolic
events, all-cause
mortality
15
months
CYP2C9,
VKORC1• Atrial fibrillation
development evaluated
every 12 months
• Warfarin associated
outcomes evaluated every
15 months
Antiplatelet therapy
associated outcomes:
stroke, myocardial
infarction, major bleed,
cardiovascular-related
death,
non-cardiovascular
related death
CYP2C19
24
months
Statin therapy associated
cardiovascular outcomes:
stroke, myocardial infarction,
cardiovascular-related
death,
non-cardiovascular-related
death
SLCO1B1
Start12
months
Methods
• Model inputs were estimated from published studies and Medicare fee schedules. All costs were inflated to 2018 US dollars. Cost and QALYs were discounted at 3% per year.
• Base-case scenario reflects current national prescribing patterns for antiplatelet and stain therapy and warfarin.
• Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations was completed using Oracle® Crystal Ball Classroom Edition, Release 11.1.2.4.
• Parameters that were varied included: disease incidence, event cost, prescription cost, outcome events, and health state utilities.
Multi-gene Testing Standard of Care Single-gene Testing
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LimitationsOnly 4 genes and 3 CVD medications were included in the multi-gene PGx testing strategy when more genes are often included in these tests.
The results likely underestimate the true benefits of multi-gene PGx tests that impact numerous additional non-CVD medications.
Generalizability is limited to U.S. Medicare patients.
Assumed genetic information would be followed 100% according to FDA and CPIC guidelines.
Assumed genetic information would be available at the time of drug prescribing and would follow Medicare patients over their lifetime.
• In the long-term, multi-gene PGx testing (CYP2C19, SLCO1B1, VKORC1, CYP2C9) was the most cost-effective intervention to help optimize medication selection for Medicare beneficiaries who are undergoing a PCI for ACS when compared to single-gene PGx testing (CYP2C19) and standard of care (no genotyping).
• Future research is needed to evaluate additional gene-drug pairs that may also be relevant for this population to obtain a more comprehensive understanding of the impact multi-gene PGx testing provides for this patient population.
Conclusions
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When patients are prescribed a drug with actionable
PGx guidance, should multi-gene or single gene PGx
testing be done?
Multi-Gene Testing
Provides genetic information to help optimize the
prescribing of an immediate drug PLUS additional
genetic information for drugs that may be prescribed
in the future.
Provides genetic information to help optimize
the prescribing of an immediate drug.
Single-Gene Testing
This cost-effectiveness analysis suggests that multi-gene testing is the preferred
strategy in patients with ACS undergoing PCI.
Acknowledgements
Tim Wiltshire, PhD
Craig Lee, PharmD, PhD
Stephanie Wheeler, PhD, MPH
Stacie Dusetzina, PhD
Deepak Voora, MD
Gracelyn Cruden, MA
Funding sources:
• American Heart Association Predoctoral Fellowship (18PRE33960079)
• UNC Eshelman Institute for Innovation grant R1020