1. The Execution and Management of a Complex Clinical Trial Elizabeth K. Walsh, RN ECTSS 2013 Conflicts of Interest Advisory Board for TAVR Administrators Study Operations Steering Committee

2. January 2007 Planning Meeting for TAVR: The Heart Team November 2007 1 st TAVR Implant November 2011 FDA approval for Inoperable October 2012 FDA approval for High Risk October 2013 Completion of Intermediate Risk enrollment Future TAVR devices and Trials to start in the US Introduction Utilization of a Best Practice Model: Crucial for the execution of a Successful Landmark Trial A Single Site Timeline

3. Methods 2007 – 2011238 Enrolled Partner 1 2011 – Present203 Enrolled Partner 2 (continuing) 2011 – Present275 Commercial Implants Over 2000 Patients Screened for TAVR

4. Data Capture Screening Baseline Index Procedure Discharge Follow up Study Exit Protocol Deviation Adverse Events Hospitalization Hemorrhage/Vascular Injury Neurological Myocardial Infarction Infection Thromboembolic Average Data Points per patient Screening to 5 Year Follow = 1840 CRF Pages = 92 (excluding AE Capture) Average Queries per Subject = 47 Tracking the Data Audit and Monitoring of the Data

5. Results Complex Patient Population 1840 Data Points collected per patient Multiple Adverse Events requiring 24 hour PI Review Resource Intense Continuing Education New Protocols and multiple Protocol Modifications Patient and Family Education Staff members throughout the hospital and outpatient Training New Research Staff –Regulatory –Safety –Meeting Trial Endpoints –Data Management –Consenting –Follow up –Inspection Readiness –Collaboration with clinical staff FDA Trials are Serious Business Follow the Rules Growth of Staff over time

6. Conclusion Since 2007 over 2000 patients screened for TAVR Heart Team Model: Strong Coordinator, Weekly Team Meetings TAVR Clinic: Key to Patient Flow Keeping up with the Volume Patient Protocols Evolved from Best Practices in Clinical Trial TAVR Model Excellent Example of Complex Clinical Trial TAVR Trial a template for transition to a commercial Program Challenging Patient Population Multiple Data Points Multiple Sub-studies Multiple protocol versions Large Volume of AEs High Profile Trial Cost Resources Intense Multiple Data locks/Deadlines Running a Complex Trial can be a heavy load What is a Complex Clinical Trial