The Vascular and Endovascular Devices Team (VEDT) in the Food and Drug Administration (FDA) Office of Cardiovascular Devices appreciates the Vascular Specialist editorial board’s offer to provide an update to the vascular community to enhance regulatory transparency and communication. In this commentary, Ronald M. Fairman, MD, Gordon Bryson, Carmen Gacchina Johnson, PhD, and Andrew Farb, MD, cover COVID-19’s impact on the team’s work, pre- and post-market data collection, physician-sponsored investigational device exemption (PS-IDE) studies, and ongoing collaborations to support timely access of innovative devices to U.S. patients. The authors are responding to a report—“Getting medical devices to market: The future might not be now, says regulatory expert”—carried in the April issue of Vascular Specialist.
The COVID-19 pandemic broadly impacted the vascular community, notably numerous challenges to initiating new and conducting ongoing medical device studies. One important example was the difficulty investigators and device manufacturers faced maintaining subject follow-up compliance to collect complete and meaningful information in support of future device marketing applications. Despite the challenges during this time, sustained collaboration between FDA review staff and study sponsors helped assure access to innovative vascular surgery devices (e.g., ascending, aortic arch, descending thoracic and thoracoabdominal aortic devices).
Two recent examples include FDA approval of the first frozen elephant trunk platform, and the first single-branch thoracic endoprosthesis for endovascular repair of descending thoracic aortic lesions that maintains blood flow into the left subclavian artery. Despite the challenges posed by COVID-19, the Office of Cardiovascular Devices worked diligently with industry sponsors to ensure novel, safe and effective devices reached the U.S. patients. In addition, there are multiple actively enrolling studies at U.S. sites for devices placed in the ascending aorta, aortic arch and thoracoabdominal aorta to treat diverse aortic pathologies.
Given the limitations in maintaining patient follow-up compliance during the COVID-19 pandemic, as well as experience with prior studies (e.g., challenges in longer-term data collection, strict selection criteria in studies not reflecting real-world device use), and in consideration of our commitment to commercialize life-saving new therapies in a timely manner, VEDT re-evaluated our approach to post-market studies. Applying the appropriate pre-market and post-market data collection balance facilitates timely patient access to important new technology without undermining patient safety. As such, there have been new efforts to identify areas for improvement in post-market data collection.
On Nov. 3, 2021, the FDA held a public meeting of the Circulatory System Devices Panel of the Medical Devices Advisory Committee to obtain advice and recommendations on the long-term safety and effectiveness of endovascular aneurysm repair (EVAR). This meeting included industry sponsors, investigators, patient advocate organizations, and physician experts. After the panel meeting, the FDA issued a letter to healthcare providers in February 2022 and has been involved in dedicated efforts to gain alignment with stakeholders on ways to strengthen post-market data collection, which are intended to allow for a better understanding of long-term outcomes with EVAR devices, help identify safety signals, and potentially support labeling expansions.
Independent of these post-market activities, it is important to address concerns regarding PS-IDEs evaluating the performance of devices in the thoracoabdominal aorta. These PS-IDEs typically study commercially available devices that are physician-modified or used for a new intended use, or devices that are commercially available outside of the U.S. If physician modification of a commercial aortic device or use of a commercial device for a new indication is being done on a routine basis, we continue to recommend an IDE should be submitted.
We recognize that there are patients with complex life-threatening aortic pathologies, and PS-IDEs are an option that has been utilized to allow access to new devices or approved devices for new indications, particularly for treatment of thoracoabdominal aortic aneurysms. PS-IDEs have helped advance device design, management of bridging stent instability, patient selection, management, and prevention of spinal cord ischemia. PS-IDEs have also refined strategies to reduce radiation exposure, improve imaging, and guide accessory device use. The results of many of these studies have been published in the Journal of Vascular Surgery (JVS) and presented at the SVS’ Vascular Annual Meeting (VAM). VEDT currently has over 30 approved PS-IDEs, and the number has been growing annually.
There are some regulatory concerns regarding PS-IDEs that can impact the availability of new beneficial therapies for patients. Typically, PS-IDEs are of limited size and scope and do not collect the definitive data needed for device approval (a reasonable assurance of safety and effectiveness). Further, PS-IDEs may have little or no industry support, such that non-clinical testing and manufacturing requirements are not met to support a marketing application. As a result, although PS-IDEs can provide important insights into device performance, the devices studied (and their physician modifications) remain investigational, and the devices are not available to treat many U.S. patients with the target clinical condition.
To address this issue, we are collaborating with investigators and manufacturers on physician-sponsored and industry-sponsored feasibility and pivotal IDE studies that will support device approval so that new safe and effective devices are available to all U.S. patients.
There has been communication with industry and physician sponsors to discuss the future of PS-IDEs and alignment on plans to bring these life-saving aortic devices to market in a timely manner. These plans include the following:
- The FDA continues to consider access to devices through PS-IDEs as long as adequate information is provided to support the IDEs (e.g., non-clinical information, individual investigator experience). When there is significant interest in device access, efforts are underway to pursue manufacturer-sponsored studies and/or marketing applications in a timely manner.
- Device manufacturers and the FDA are working together to limit the number of PS-IDEs so as not to create situations that would in effect constitute commercializing an investigational device.
- Stakeholders are collaborating to determine if existing data is adequate to support pivotal studies or marketing applications.
- The FDA is encouraging physicians treating patients with unmet clinical needs to engage in pivotal studies for next-generation devices.
As illustrated in the above framework, the FDA remains committed to promoting timely access to safe and effective devices. The FDA remains supportive of PS-IDEs when appropriately justified, and we would like to assure the community that there have been no measures to halt existing PS-IDEs provided the results are encouraging. We are regularly accessible to practicing physicians to discuss unmet needs of their patients and how we may work together to address them, and we encourage engagement with the FDA on such proposals through the Q-submission process.
We are also currently working with the SVS on updates to the PS-IDE template for treatment of complex aortic pathologies. We encourage physicians who may pursue a PS-IDE to obtain the template from the Society ([email protected]) as it provides a clear outline, pre-populated content, and suggestions for providing study-specific information.
We acknowledge there are increasing numbers of well-trained physicians with experience and sophisticated skills treating patients with complex aortic pathologies using investigational or modified devices. Yet, after leaving their training programs where they may have used devices under an IDE, physicians may experience limitations to access investigational devices and techniques for endovascular treatment of complex cases. The FDA does not encourage physician modifications of commercialized endovascular grafts but notes that the routine practice of physician modification of devices should be conducted under an IDE.
VEDT is hopeful that the need for physician-modified devices will be substantially decreased as device manufacturers pursue clinical studies for devices meeting patient needs and as devices currently under study come to market with data to support a reasonable assurance of safety and effectiveness.
In summary, the FDA Office of Cardiovascular Devices is focused on supporting and enhancing patients’ timely access to safe and effective cardiovascular devices. The FDA’s mission, enthusiasm, and the commitment of VEDT to advance medical device innovation to bring safe and effective vascular surgery devices to market—thereby supporting and improving public health—remain steadfast. We seek efficient clinical studies and commercialization of innovative technology addressing unmet needs for U.S. patients, and we are engaged with external stakeholders to navigate paths to achieve these goals. Continued stakeholder collaboration on pivotal studies, marketing applications, and robust post-market data collection plans are critical to get devices to market to address unmet needs.
We are dedicated to working with all stakeholders in order to bring life-saving and innovative devices to the U.S. market to benefit patients.
It was a pleasure for many VEDT reviewers to participate in the recent VAM 2023 and engage with many of you. We look forward to the ongoing collaborations. Thank you again for this opportunity to reach out to the broader vascular community with this update.
Disclaimer: This article reflects the views of the authors and should not be construed to represent the FDA’s views or policies. Ronald M. Fairman, MD, is the FDA’s VEDT medical officer and a former SVS president. Gordon Bryson is an FDA biomedical engineer; Carmen Gacchina Johnson, PhD, the organization’s assistant director for vascular and endovascular devices; and Andrew Farb, MD, its chief medical officer in the Division of Cardiovascular Devices.