CIRCULATORY SUPPORT DEVICES PANEL Tuesday, June 8, 2004

1. DRAFT

2. CIRCULATORY SUPPORT DEVICES PANELTuesday, June 8, 2004 World Heart N100PC(q) LVAS P980012/S004/A007 DRAFT

3. FDA REVIEW TEAM • C. Ahn (statistician) • M. Berman (lead reviewer) • I. Pina (heart failure cardiologist) • J. Swain (cardiac surgeon) DRAFT

4. PROPOSED EXPANDED INDICATION FOR USE The LVAS is intended for use as a short or longterm bridge to transplantation in cardiac transplant candidates, and in patients with relative contraindication to transplantation who are expected to become transplant candidates with mechanical circulatory support, at risk of imminent death from nonreversible left ventricular failure. The LVAS is indicated for use both inside and outside of the hospital. DRAFT

5. INDICATIONS(S) FOR USE21 CFR 814.20(b)(3)(i) • A general description of the disease or condition the device will diagnose, treat, prevent, cure, or mitigate, including a description of the patient population for which the device is intended. DRAFT

6. INDICATIONS(S) FOR USE21 CFR 814.20(b)(3)(i) • Description of disease? • HF, non-reversible LV failure, risk of imminent death • Description of patient population? • Candidates for cardiac transplant • Relative contraindication to transplant • Expected to become transplant candidates with mechanical circulatory support DRAFT

7. FDA MUST DETERMINE • Reasonable assurance of safety and effectiveness (Act, §513(a)(1)(C)). • Safety and effectiveness are to be determined with respect to … (Act, §513(a)(2)) • Patients for whose use the device is intended • Conditions of use prescribed, recommended, or suggested • Probable benefit vs. probable injury DRAFT

8. DEVICE DESCRIPTION • Implanted components • Blood pump • Valved conduits • P/O percutaneous tube • External components • Controller • Battery packs • Or other power sources • Accessories DRAFT

9. Source: Operator’s Manual DRAFT

10. PRECLINICAL EVALUATION FOR BTTDetermined to be Satisfactory for BTT Indication • Manufacturing • Sterilization, packaging, shelf life, shipping • Biocompatibility • Software • Mechanical safety • Electrical safety and EMC • Hydrodynamic characterization of pump • Battery performance • Alarms DRAFT

11. REMAINING FDA CONCERNS • Clinical • Patients evaluated ≠ patients indicated • “relative contraindication” • “expected to become transplant candidates” • “short or long term” • Statistical • Comparability of selected treatment and control groups • Combining patients with single and multiple “relative contraindications” • Are selected groups representative of patient population? DRAFT

12. CLINICAL CONCERNS • “Short or long term” • 160 (of 190) BTT LVAS patients ≤ 6 months • Of 30 LVAS patients > 6 months • 15 LVAS patients ≥1 year • 4 LVAS patients ≥ 2 years • “Relative contraindication” • Why these 7 parameters? • Why these chosen thresholds? • “Expected to become” • These patients were transplant candidates • No objective evidence of reversal/normalization of “relative contraindication” DRAFT

13. STATISTICAL CONCERNS • Comparability of selected patient sub-groups from BTT clinical trial • Covariates not matched • Combining patients with individual and multiple “relative contraindications for statistical analysis • Sub-groups may not be representative of intended patient population DRAFT