1. Cost Effectiveness of Genetic Testing in Monogenic Diabetes Rochelle Naylor, MD Section 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 in GCK, HNF1A, HNF1B and HNF4A 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. http://www.tutor2u.net/ Health Care Economics

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

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

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

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 InterventionICER Intensive glucose control $41,384/QALY Intensive blood pressure control -$1,959/QALY Statin$51,889/QALY 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 ABCC8 are 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 GreeleyElbert Huang Priya John

19. Genetic Testing in Neonatal Diabetes is Cost-Effective Diabetes Care. 2011 Mar;34(3):622-7. Epub 2011 Jan 27. 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.

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? Huge cost savings when defect highly prevalent (<6 mo at Dx) Still cost-saving when mutations present in 3% of patients (?<9 mo at Dx?) Threshold Analysis of Prevalence

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

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

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 diseaseTesting corrects classification of known disease Course of action uncertainClear 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 unclearAvailable 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 Siri Greeley Louis Philipson David Carmody Priya John Graeme Bell Elbert Huang Aaron Winn The Lab The Families Referring Clinicians

44. THANK YOU