Author + information
- Received October 20, 2010
- Accepted October 22, 2010
- Published online January 18, 2011.
- Matthew G. Hillebrenner⁎ (, )
- Julie A. Swain and
- Bram Zuckerman
- ↵⁎Reprint requests and correspondence:
Matthew G. Hillebrenner, Office of Device Evaluation, Center for Devices and Radiological Health, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, WO66-1232, Silver Spring, Maryland 20993-0002
The Food and Drug Administration (FDA) is responsible for protecting and promoting the public health of U.S. citizens. In keeping with this mission, FDA's Center for Devices and Radiological Health (CDRH) is tasked with assuring the safety, effectiveness, and quality of medical devices, assuring the safety of radiation-emitting products, fostering innovation, and providing the public with accurate, science-based information about the products we oversee, throughout the total product life cycle (1). In order to enhance our ability to fulfill our mission, CDRH developed a strategic plan to identify priority areas for 2010. One of our goals is to proactively help facilitate medical device innovation and address unmet public health needs (2). To accomplish this objective, CDRH believes it is critical to leverage our regulatory authority and unique understanding of the products we oversee, as well as to establish strong working relationships with our partners in the federal government and external constituencies, and to advance innovative solutions to critical public health challenges (2).
One example of this type of collaboration is participation by members of CDRH's Division of Cardiovascular Devices in the efforts of the Valve Academic Research Consortium (VARC), an independent group that includes members of academic research organizations, cardiovascular professional societies (clinical and interventional cardiology and cardiothoracic surgery), and the medical device industry. The Valve Academic Research Consortium was established in response to the burgeoning interest in transcatheter aortic valve implantation (TAVI) by the medical community. Transcatheter aortic valve implantation represents a potential breakthrough technology, offering a less invasive catheter-based treatment option for patients with severe aortic stenosis, some of whom may not be candidates for open heart surgery. Although a less invasive option to open surgery has many attractive features, TAVI involves highly novel devices and presents many complex challenges in the design, conduct, and interpretation of clinical trials.
To address some of these challenges, VARC employed a multidisciplinary approach to develop consensus regarding standardized definitions for adverse events and recommendations for single and composite endpoints that reflect appropriate device-, procedure-, and patient-related safety and effectiveness measures for TAVI clinical trials that enroll high-risk patients. This approach resulted in a rigorous but clinically appropriate and reasonable set of recommendations. The FDA anticipates incorporating many of the recommendations put forth in the consensus document into the TAVI clinical trials reviewed and regulated by the Agency. As such, we believe that the VARC document can help improve the efficiency with which TAVI clinical trials are designed and executed.
We continue to encourage sponsors to contact the Agency early in device development to begin discussions regarding specific endpoints for studies intended to support FDA approval. While a common set of definitions and endpoints is very helpful, critical trial design elements may depend on the particular device and patient population being studied. Also, many of the most difficult challenges associated with these devices involve preclinical testing issues due to the anatomically and hemodynamically challenging aortic environment where these devices must perform well for long periods of time. Therefore, it is extremely important that sponsors understand FDA's preclinical testing requirements as early as possible so that adequate fatigue testing, finite element analysis modeling, and animal studies can be completed for these innovative devices. It is our hope that publication of the VARC document will encourage sponsors and investigators to make use of early interaction with the Agency. For this field to mature in the USA, it is essential that FDA, sponsors, and investigators continue to collaborate closely to develop high-quality clinical data that ultimately results in benefits for patients.
The Food and Drug Administration also acknowledges the importance of the global approach adopted by VARC, both in terms of geography (representatives from the scientific community in both USA and Europe) and expertise (surgeons, interventional cardiologists, clinical cardiologists, clinical trialists, and other allied specialists), which we believe was instrumental to the success of this initial undertaking. Such a process allowed for an open and balanced discussion of complex issues. There are multiple areas of medicine in which this collegial and comprehensive approach would be beneficial. Finally, the consensus report represents the first step in what promises to be a dynamic process, and the Agency looks forward to continued involvement with VARC as the technology and clinical application of TAVI evolves.
Funding was provided by Cardialysis BV on behalf of the Valve Academic Research Consortium. This work represents the professional opinion of the authors and is not an official document, agency guidance or policy of the U.S. Government, the Department of Health and Human Services, or the Food and Drug Administration, nor should any official endorsement be inferred. The article has been co-published in the European Heart Journal.
- Received October 20, 2010.
- Accepted October 22, 2010.
- American College of Cardiology Foundation
- ↵CDRH Strategic Planning. Last updated 20 January 2010 http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHVisionandMission/default.htm. Accessed September 7, 2010.
- ↵CDRH FY 2010 Strategic Priorities. Last updated 3 September 2010 http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHVisionandMission/ucm197647.htm. Accessed September 7, 2010.