1. Cost-Effectiveness of Left Ventricular Assist Devices (LVADs) as Permanent Implants for End-Stage Heart Failure David Samson Blue Cross and Blue Shield Association Technology Evaluation Center, University at Albany Thanks to:Alan M. Garber Stanford University Gillian Sanders Duke University Naomi Aronson Blue Cross and Blue Shield Association Technology Evaluation Center Copyright 2004 Blue Cross Blue Shield Association

2. Rose et al. NEJM, 2001; 345:1435

3. REMATCH Trial REMATCH: destination therapy, in contrast to bridge to transplant 129 patients with NYHA Class IV end-stage heart failure, contraindications for heart transplantation, randomized to LVAD or optimal medical management (OMM) Median survival: LVAD - 408 d, OMM - 150 d ( 8.5 mo, p=0.001) Rate of all serious adverse events per patient-yr: LVAD - 6.45, OMM - 2.75, rate ratio (95% CI): 2.35 (1.86 - 2.95) Copyright 2004 Blue Cross Blue Shield Association

4. REMATCH Trial Copyright 2004 Blue Cross Blue Shield Association CDRH- FDA, CSDAP, 03/04/02

5. REMATCH Trial 1 yr median NYHA Class: LVAD - II, OMM - IV (p<0.001) 1 yr mean SF-36 PF: LVAD - 46, OMM - 21 (p=0.01) Copyright 2004 Blue Cross Blue Shield Association Class I: No limitation on physical activity (sx > ordinary activity) Class II: Slight limitation on physical activity (sx ordinary activity) Class III: Marked limitation on physical activity (sx < ordinary activity) Class IV: Inability to carry on physical activity (sx at rest)

6. REMATCH Trial Copyright 2004 Blue Cross Blue Shield Association Thoratec, FDA, CSDAP, 03/04/02

7. Structural Components of CEA Time horizon, perspective:Lifetime (3 years), payor Patient population, setting:REMATCH patient selection, sites Strategies:LVAD, OMM Markov model: 2-state (analogous to 3-state) Quality of life focus:NYHA functional class categories Valuing of Costs:2002 $ US Copyright 2004 Blue Cross Blue Shield Association

8. Markov Model Copyright 2004 Blue Cross Blue Shield Association AliveDead p 11 1 NYHA III/IV p 11 p 22 Dead NYHA I/II p 12 p 13 p 23 1 p 21 2-State: 3-State:

9. Cycle-Specific Calculation of QALYs, Costs QALY t = S t [(P I/II *U I/II )+(P III/IV *U III/IV )] t /12 C t = S t [(P rehosp *C rehosp )+(P outpt *C outpt )] Copyright 2004 Blue Cross Blue Shield Association t = monthly cycle S t = survival probability P I/II, P III/IV = probability of being in NYHA class categories U I/II, U III/IV = utility of being in NYHA class categories P rehosp, P outpt = probability of being rehospitalized, outpatient C rehosp, C outpt = cost of being rehospitalized, outpatient

10. Parameter Estimates Survival, LVAD:OMMHR=0.5295% CI: 0.34, 0.78 Survival extrapolationinterpolationstop & drop, 2 sets to 0% @ 3 yr parametric models NYHA I/II utility0.810.50 - 1.00 NYHA III/IV utility0.550.30 - 0.80 Copyright 2004 Blue Cross Blue Shield Association

11. Parameter Estimates LVAD P rehosp 0.220.10 - 0.35 OMM P rehosp 0.150.05 - 0.30 LVAD C implant $277,001$125K - $425K LVAD/OMM C rehosp $39,896$10K - $70K LVAD/OMM C outpt $1,719$250 - $3,250 Discount, costs/utilities3%1% - 5% Copyright 2004 Blue Cross Blue Shield Association

12. Results: Baseline, Sensitivity Analysis on Survival Relation Copyright 2004 Blue Cross Blue Shield Association

13. Sensitivity Analysis on Survival Extrapolation Copyright 2004 Blue Cross Blue Shield Association

14. Sensitivity Analysis on Cost of Implantation Copyright 2004 Blue Cross Blue Shield Association

15. Sensitivity Analysis on Cost of Implantation Copyright 2004 Blue Cross Blue Shield Association

16. Sensitivity Analysis on NYHA Utilities Copyright 2004 Blue Cross Blue Shield Association

17. Sensitivity Analysis on NYHA Utilities Copyright 2004 Blue Cross Blue Shield Association

18. Sensitivity Analysis on NYHA Utilities Copyright 2004 Blue Cross Blue Shield Association

19. Sensitivity Analysis on Rehospitalization/Outpatient Costs Copyright 2004 Blue Cross Blue Shield Association

20. Sensitivity Analysis on Probability of Rehospitalization Copyright 2004 Blue Cross Blue Shield Association

21. Sensitivity Analysis on Discount Rate Copyright 2004 Blue Cross Blue Shield Association

22. Conclusions CEA results most sensitive to cost of LVAD implantation In 1-way and 2-way sensitivity analyses, ICERs < $500K/QALY depended on unrealistic assumptions, especially about cost of LVAD implantation Destination LVADs exceed common CE standards Results raise questions of resource use for end-of-life care Copyright 2004 Blue Cross Blue Shield Association

23. References CDRH-FDA. Presentation to FDA-CSDAP, March 4, 2002. Frazier et al. Ann Surg, 1995;222(3):327-38. Frazier et al. Ann Thorac Surg, 1994;57:1416-22. Gelijns et al. Ann Thorac Surg, 1997;64:1312-9. Moskowitz et al. Ann Thorac Surg, 2001;71:S195-8. Moskowitz et al. Ann Thorac Surg, 1997;64:1764-9. Oz et al. Ann Surg, 2003;238(4):577-85. Rose et al. N Engl J Med, 2001;345(20):1435-43. Samson. TEC, 2004;19(2):1-36 (bcbs.com/tec/vol19/19_02.html) Thoratec. Presentation to FDA-CSDAP, March 4, 2002. Copyright 2004 Blue Cross Blue Shield Association