FDAs Clinical Goal Lines IDEs PMAs HDEs for

FDA’s Clinical Goal Lines: IDEs, PMAs, HDEs for Transcatheter Heart Valves Sonna Patel-Raman, Ph. D Acting Branch Chief Circulatory Support and Prosthetics Devices Branch Division of Cardiovascular Devices Office of Device Evaluation

Sonna Patel-Raman, Ph. D I have no real or apparent conflicts of interest to report.

FDA - Public Health Mission • FDA - To assure that devices are safe and effective for their intended uses and that labeling and packaging is truthful and informative • Regulation is a balancing act – – Benefit - Get safe and effective devices to market as quickly as possible and ensure that devices currently on the market remain safe and effective – Risk – Harm to patient if devices are not appropriately evaluated prior to marketing and unsafe use after approval 4

Risk-Based Paradigm. Device Classifications – Class I – General Controls – Most exempt from premarket submission – Class II – Special Controls – Premarket Notification [510(k)] – Class III – Premarket Approval – Require Premarket Application [PMA] 5

Pre-Submission (for IDE) • Pre-clinical testing summary • Clearly defined intended patient population – Inoperable/Extreme Risk – High Risk – Intermediate Risk • Endpoints – mortality, vascular complications, neurological events, hospitalization • Statistical analysis plan 6

IDE – Investigational Device Exemption • Trial conduct • Appropriate registry development to capture: – Valve-in-valve – Unicuspid/bicuspid AV – Moderate/severe MR • Utilization of pre-specified AE definitions • Changes during IDE study (consider presubmission) – Addition of another valve size – Minor device modifications – Protocol modifications 7

PMA – Premarket Application and HDE – Humanitarian Device Exemption • Labeling of device should reflect clinical data collected during IDE • PMA – reasonable assurance of safety and effectiveness • HDE – reasonable assurance of safety and probable benefit – Intended to benefit patients in the treatment or diagnosis of diseases or conditions that affect fewer than 4, 000 individuals in the U. S. – Humanitarian Use Designation required (HUD) from Office of Orphan Products Development 8

Conclusions • THV class III devices • Pre-Submission – interact early and often • IDE – well designed, well conducted, well analyzed • Two marketing applications – PMA - safety and effectiveness • Statistically robust clinical trial design for intended population – HDE – safety and probable benefit • Smaller clinical study due to limited patient population • Evaluation of totality of the data determines benefit/risk profile 9

For copies of slide, please email: Sonna. Patel@fda. hhs. gov