1. Stephen Brecker St. George’s Hospital, London, United Kingdom S Mealing, J Eaton, M Sculpher Oxford Outcomes (ICON), Oxford, United Kingdom Johan Bosmans University Hospital Antwerp, Antwerp, Belgium Ulrich Gerckens Gemeinschaftskrankenhaus Bonn, Bonn, Germany Peter Wenaweser University Hospital Bern, Bern, Switzerland Corrado Tamburino Ferrarotto Hospital, University of Catania, Catania, Italy Sabine Bleiziffer German Heart Center, Munich, Germany Nicolo Piazza German Heart Center, Munich, Germany Neil Moat Royal Brompton Hospital, London, United Kingdom Pascale Brasseur Medtronic, Tolochenaz, Switzerland Rachele Busca Medtronic, Tolochenaz, Switzerland Axel Linke University of Leipzig Heart Center, Leipzig, Germany (on behalf of the ADVANCE Investigators) UC201400511 EE

2. Potential Conflicts of Interest Speaker's name: Stephen Brecker  I have the following potential conflicts of interest to report: Consultant: Medtronic, Inc., St. Jude Medical The project was funded by an unrestricted grant from Medtronic. No influence was exerted on the design of the model or presentation of results.

3. Principles of Health Economics Project Rationale Model Structure/ Inputs Key Results/ Outputs Conclusions ADVANCE | Outline

4. COSTS BENEFITS COSTS: Direct, Indirect BENEFITS: Prolonged life, improved quality of life, less hospitalisations, etc. ADVANCE | Principles of Health Economics

5. An existing cost-utility model was updated using data from the ADVANCE Study to: – Capture costs and effectiveness of TAVI – Evaluate the impact on the cost/QALY gained of using survival estimates from different patient cohorts – Explore which parameters in the model most influence results – Re-evaluate funding and prioritise treatments as clinical practice evolves using pragmatic follow-up studies based on real-world evidence ADVANCE | Rationale – Updated Existing Model

6. ADVANCE | Model Structure

7. ADVANCE | Key Model Inputs

8. In the model the hospital cost for the TAVI index procedure was £23,048 ADVANCE | Key Model Cost Inputs

9. TAVI: ADVANCE 12 month data; MM: 36 month PARTNER B data ADVANCE and PARTNER B data extrapolated Weibull functions No proportional hazards assumption used – arms modelled independently ADVANCE | Key Results: Mortality

10. ADVANCE | Results

11. ADVANCE | Cost-effectiveness Plane

12. ADVANCE | Effect of Varying Inputs

13. SUBGROUP ANALYSES

14. Observed data taken from the ADVANCE Study TAVI patients with EuroSCORE ≥20%, survival data for the medically managed patients was informed by the PARTNER B Trial ADVANCE | Mortality in Patients with EuroSCORE ≥20 ADVANCE and PARTNER B data extrapolated Weibull functions

15. ADVANCE | Results – Subgroup EuroSCORE≥20

16. ADVANCE | Cost-effectiveness Plane Subgroup EuroSCORE≥20 Incremental Costs

17. Survival benefit of subgroup with EuroSCORE ≥20 constrained so all TAVI recipients are dead at 10 years, median survival approx. 3.5 yrs ADVANCE | Truncation of Survival Benefit in Subgroup (EuroSCORE ≥20)

18. These data demonstrate that TAVI with the CoreValve System is cost effective, when health economic metrics are applied to the real-world ADVANCE Study. The average cost per QALY gained for the overall cohort is £11,265 and this rises to £13,778 when applied to the subgroup with EuroSCORE ≥20% in the study — both of these figures are well within the benchmark used by national regulatory bodies in the UK and elsewhere. ADVANCE | Conclusions