Rochelle Naylor, MD Section of Adult and Pediatric Endocrinology, Diabetes & Metabolism

1. Cost Effectiveness of Genetic Testing in Monogenic Diabetes Rochelle Naylor, MDSection of Adult and Pediatric Endocrinology, Diabetes & Metabolism The University of Chicago Medicine

2. Disclosures • Research funding: American Diabetes Association, Kovler Family Foundation • The University of Chicago receives royalties from Athena Diagnostics for genetic testing for mutations inGCK, HNF1A,HNF1B andHNF4A • I will be discussing the off-label use of sulfonylureas

3. Disclaimer • I am not an economist…. • I am: • A pediatric endocrinologist • A researcher in the genetics of diabetes • An advocate

4. Outline • Health Care Costs • Primer on cost effectiveness analysis (CEA) • CEA in neonatal monogenic diabetes • CEA in subtypes of MODY • Health Care Implications

5. US Health Care Expenditures

6. Bigger is Not Always Better http://www.commonwealthfund.org/

7. The Cost of Diabetes

8. Health Care Economics http://www.tutor2u.net/

9. Health Care Economics- An Uncomfortable Truth http://www.asianhhm.com/

10. 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 Quality-Adjusted Life Years (QALYs) • Expressed as the Incremental Cost- Effectiveness Ratio (ICER)

11. The Cost-Effectiveness Plane http://neoreviews.aappublications.org/

12. The Cost-Effectiveness Plane $50,000/ QALY http://europace.oxfordjournals.org/

13. The ABCs of Good Diabetes Care • HbA1c • Blood Pressure • Cholesterol http://www.eatinghabits.org/good-eating-habits/healthy-eating-tips.html

14. ICER of Components of Diabetes Care CDC Cost-Effectiveness Group. JAMA. 2002

15. Monogenic Diabetes

16. 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

17. Neonatal Diabetes • Neonatal diabetes is rare, but has an obvious phenotype • Mutations in KCNJ11 and ABCC8are a frequent cause of neonatal diabetes • The majority of patients can switch from insulin to sulfonylureas Is genetic testing cost-effective?

18. Cost-Effectiveness Analysis of Neonatal Diabetes Siri Greeley Priya John Elbert Huang

19. 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.

20. Objectives Total Cost SAVINGS after 30 years: $-30,437 Health Benefit: Also a gain in QALYs ie Testing policy is DOMINANT

21. “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)

22. MODY http://www.empowernetwork.com/

23. 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

24. 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

25. Diagnosed MODY- The Tip of the Iceberg http://www.pvisoftware.com/b

27. Identifying Patients MonogenicDiabetes.org

28. Identifying Patients

29. Kovler Monogenic Diabetes Registry

30. 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!

31. 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

32. GCK (35% of MODY) No Treatment (100%) Continued Sulfonylurea Sulfonylurea (90%) Positive for MODY (2%) HNF1A/4A (65% of MODY) Test for MODY Sulfonylurea failure over time* Treated as Type 2 Diabetes (10%) Negative for MODY (98%) Type 2 Diabetes Diagnosed at age 25-40 Yr No Treatment (15%) Pills (57%) Undetected GCK No MODY Testing Insulin (14%) Undetected HNF1A/4A Insulin + Pills (14%) Type 2 Diabetes

33. Outcome measures • Costs • Genetic testing • Treatment • Complications • Quality-adjusted life years (QALYs) • Treatment burden • Complications • Outcome expressed as the incremental cost-effectiveness ratio (ICER, Δ$/ΔQALY)

34. Base Case Results

35. Sensitivity Analyses

36. Genetic Testing Becomes Cost Saving as the Pick-up Rate of MODY Increases • 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%

37. Results • Testing in unselected patients is not cost-effective • Small changes in prevalence make genetic testing cost-effective • Decreased genetic testing costs make testing cost-effective

38. 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)

39. Selecting Patients for Testing

41. 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 Treatment is cheaper than conventional T2DM therapies Potential interventions are costly Increases health care system interactions Health care system interactions unchanged (HNF1A, 4A) or decreased (GCK) Targeted population unclear Available clinical calculators and prediction models

42. 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

43. Acknowledgments Priya John Louis Philipson Siri Greeley Graeme Bell David Carmody Aaron Winn Elbert Huang Referring Clinicians The Lab The Families

44. THANK YOU