Cost Effectiveness of Genetic
Testing in Monogenic Diabetes
Rochelle Naylor, MD
Section of Adult and Pediatric
Endocrinology, Diabetes & Metabolism
The University of Chicago Medicine
Disclosures
• Research funding: American Diabetes
Association, Kovler Family Foundation
• The University of Chicago receives royalties
from Athena Diagnostics for genetic testing for
mutations in GCK, HNF1A, HNF1B and HNF4A
• I will be discussing the off-label use of
sulfonylureas
Disclaimer
• I am not an economist….
• I am:
– A pediatric endocrinologist
– A researcher in the genetics of diabetes
– An advocate
Outline
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Health Care Costs
Primer on cost effectiveness analysis (CEA)
CEA in neonatal monogenic diabetes
CEA in subtypes of MODY
Health Care Implications
US Health Care Expenditures
Bigger is Not Always Better
The Cost of Diabetes
Health Care Economics
http://www.tutor2u.net/
Health Care Economics- An
Uncomfortable Truth
http://www.asianhhm.com/
Cost-Effective Analysis
• Used to estimate the ratio between the cost
and the benefits of a health intervention
• Costs are measured in monetary units
• Benefits are measured typically in QualityAdjusted Life Years (QALYs)
• Expressed as the Incremental CostEffectiveness Ratio (ICER)
The Cost-Effectiveness Plane
http://neoreviews.aappublications.org/
The Cost-Effectiveness Plane
$50,000/ QALY
http://europace.oxfordjournals.org/
The ABCs of Good Diabetes Care
• HbA1c
• Blood Pressure
• Cholesterol
http://www.eatinghabits.org/good-eating-habits/healthy-eating-tips.html
ICER of Components of Diabetes Care
Intervention
Intensive glucose
control
Intensive blood
pressure control
Statin
CDC Cost-Effectiveness Group. JAMA. 2002
ICER
$41,384/QALY
-$1,959/QALY
$51,889/QALY
MONOGENIC DIABETES
Clinical Implications of a Genetic
Diagnosis
• Treatment
– Neonatal Diabetes
• KCNJ11 - high dose sulfonylurea
• ABCC8 – high dose sulfonylurea
– MODY
• GCK/MODY2 – no treatment except possibly during
pregnancy
• HNF1A/MODY3- low dose sulfonylurea
• HNF4A/MODY1- low dose sulfonylurea
• Genetic counseling
Neonatal Diabetes
• Neonatal diabetes is rare, but has an obvious
phenotype
• Mutations in KCNJ11 and ABCC8 are a
frequent cause of neonatal diabetes
• The majority of patients can switch from
insulin to sulfonylureas
Is genetic testing cost-effective?
Cost-Effectiveness Analysis of Neonatal
Diabetes
Siri Greeley
Priya John
Elbert Huang
Genetic Testing in Neonatal Diabetes is
Cost-Effective
CONCLUSIONS—Genetic testing in neonatal diabetes improves quality of life
and lowers costs. This paradigmatic case study highlights the potential
economic impact of applying the concepts of personalized genetic
medicine to other disorders in the future.
Diabetes Care. 2011 Mar;34(3):622-7. Epub 2011 Jan 27.
Objectives
Total Cost SAVINGS after 30 years:
$-30,437
Health Benefit:
Also a gain in QALYs
ie
Testing policy is DOMINANT
“Sweet-spot”
for screening?
Threshold Analysis
of Prevalence
Still cost-saving when mutations present
in 3% of patients (?<9 mo at Dx?)
Huge cost savings when defect
highly prevalent (<6 mo at Dx)
http://www.empowernetwork.com/
MODY- An Opportunity for
Personalized Genetic Medicine
• HNF1A-, HNF4A-MODY
– First line therapy is sulfonylurea pills
– Clinical studies has demonstrated stable HbA1c
• GCK-MODY
– Pharmacologic treatment doesn’t change HbA1c
and is almost never needed
• Appropriate first-line therapy is less clear in
other MODY causes
Barriers to Genetic Testing for MODY
• Identifying patients who may have MODY
• Obtaining Genetic Testing
– Which genes to test?
– Not simple to order the test
• No check list
– Limited insurance coverage and prohibitive cost of
genetic testing
Diagnosed MODY- The Tip of the
Iceberg
http://www.pvisoftware.com/b
Identifying Patients
MonogenicDiabetes.org
Identifying Patients
Kovler Monogenic Diabetes Registry
Current Age
Median (range)
15.4 (0-75) yrs
Age at Diagnosis
Median (range)
2.2 (0-62.1) yrs
Gender
Female
47.2%
Ethnicity (Self reported)
Genes
Cases
KCNJ11
74
INS
21
ABCC8
19
6q24-Related
20
GCK
125
HNF1A
50
Non Hispanic White
60.3%
HNF4A
5
Non Hispanic Black
5.0%
HNF1B
2
4.0%
PDX1
2
Asian
3.6%
EIF2AK3
4
Mixed/other
5.8%
FOXP3
6
Not reported
21.3%
GATA6
4
INSR
1
Hispanic
Registration Source
Physician referral
59.8%
Intron 2 INS
1
Web searching
22.4%
CFTR
1
News report
3.1%
RFX6
1
Friend/Family
8.5%
IER3IP1
1
Other
6.2%
Chromosomal
2
translocations
Genetic Testing for MODY
• Who should be tested?
– MODY misdiagnosed as type 2 diabetes and sometimes type 1
diabetes.
– Mutations can be inherited (commonly) or de novo (rarely).
• What genes should be tested?
– Most common causes of MODY are mutations in GCK, HNF1A
and HNF4A.
• Is genetic testing good healthcare policy?
– Change from expensive therapy to cheaper therapy – saves
money.
– If you have a GCK mutation, you DO NOT have type 2 diabetes
and you do not need any drugs or a diabetes doctor!
Cost analysis of MODY screening
• Objective: To evaluate the cost-effectiveness
of a genetic testing policy for HNF1A-, HNF4A-,
and GCK-MODY in a hypothetical cohort of
patients with type 2 diabetes
GCK
(35% of MODY)
No Treatment
(100%)
Sulfonylurea
(90%)
Positive for MODY (2%)
Continued
Sulfonylurea
HNF1A/4A
(65% of MODY)
Test for MODY
Negative for
MODY (98%)
Type 2 Diabetes
Diagnosed at
age 25-40 Yr
Treated as
Type 2 Diabetes
(10%)
Sulfonylurea
failure over time*
No Treatment
(15%)
Undetected
GCK
No MODY
Testing
Pills (57%)
Insulin (14%)
Undetected
HNF1A/4A
Type 2
Diabetes
Insulin + Pills
(14%)
Outcome measures
• Costs
– Genetic testing
– Treatment
– Complications
• Quality-adjusted life years (QALYs)
– Treatment burden
– Complications
• Outcome expressed as the incremental costeffectiveness ratio (ICER, Δ$/ΔQALY)
Base Case Results
Sensitivity Analyses
Genetic Testing Becomes Cost Saving
as the Pick-up Rate of MODY Increases
ICER ($/QALY)
500000
400000
Genetic testing is
• Cost-effective (ICER ≈ $50,000) if the
pick-up rate is 6%; and
• Cost-saving (ICER < $0) if the pick-up
rate is 31%
300000
200000
100000
0
0
10
20
30
MODY prevalance (%)
40
Results
• Testing in unselected patients is not costeffective
• Small changes in prevalence make genetic
testing cost-effective
• Decreased genetic testing costs make testing
cost-effective
Genetic Testing for MODY
• In the context of health care costs in the United States,
routine genetic screening for GCK-, HNF1A- and
HNF4A-MODY in incident cases of type 2 diabetes is
a cost-effective use of personalized genetic medicine if we
can
– Preselect patients for testing so pick-up rate increases - a MODY
calculator (physician?)
or
– Reduce the cost of the test ($2,500 to $700)
SELECTING PATIENTS FOR TESTING
Implications of a MODY testing policy
“Typical” Genetic Testing Scenario
MODY Genetic Testing Scenario
Testing identifies risk for disease
Testing corrects classification of known
disease
Course of action uncertain
Clear treatment plan with
demonstrated efficacy
Potential interventions are costly
Treatment is cheaper than
conventional T2DM therapies
Increases health care system
interactions
Health care system interactions
unchanged (HNF1A, 4A) or decreased
(GCK)
Targeted population unclear
Available clinical calculators and
prediction models
Conclusions
• Monogenic diabetes is an opportunity for personalized
genetic medicine
• Barriers to diagnosis include:
– Identifying people and obtaining genetic testing
• Opportunities to identify and follow patients exist
– Kovler Monogenic Diabetes Registry
• Cost analysis supports a policy of coverage for neonatal
diabetes and MODY genetic testing in targeted
populations
• Technologic advances should increase access to genetic
testing for monogenic diabetes
Acknowledgments
Priya
John
David
Carmody
Louis
Philipson
Siri
Greeley
Graeme
Bell
Elbert
Huang
Referring Clinicians
The Lab
The Families
Aaron
Winn
THANK YOU