Dorothy B. Abel

Guidelines for development and use of transluminally placed endovascular prosthetic grafts in the arterial system

THE feasibility of placing prosthetic grafts within the arterial tree by inserting them via a remote site, guiding them intraluminally to the appropriate location, and fixing them there with attachment systems, such as a variety of expandable stents, has been demonstrated in animals and human subjects (1–3). There is a potential for these transluminally placed endovascular grafts (TPEGs) to provide improved treatment for a variety of arterial lesions including aneurysms, traumatic injuries, and arteriosclerotic occlusions. TPEG repairs of all three kinds of lesions have been carried out at various levels of the arterial tree with short-term success (1,4–17). Because TPEG repairs can be performed less invasively, their risks and costs may be less than those of standard vascular graft operations. They will, therefore, be extremely attractive to both patients and physicians, and consequently there will be enormous pressures to develop and use these devices rapidly. The purpose of this document is to foster the development of safe, effective devices for performing TPEG repairs of various arterial lesions at all levels of the arterial tree. To this end, it will provide guidelines for the careful and structured evaluation and monitoring that is necessary to document the safety, efficacy, and effectiveness of these devices in various settings before they undergo widespread clinical use. Although these guidelines are not a regulatory document, they are intended to help avoid premature and potentially harmful usage of TPEGs.

Innovative postmarket device evaluation using a quality registry to monitor thoracic endovascular aortic repair in the treatment of aortic dissection

Objective: United States Food and Drug Administration (FDA)‐mandated postapproval studies have long been a mainstay of the continued evaluation of high‐risk medical devices after initial marketing approval; however, these studies often present challenges related to patient/physician recruitment and retention. Retrospective single‐center studies also do not fully represent the spectrum of real‐world performance nor are they likely to have a sufficiently large enough sample size to detect important signals. In recent years, The FDA Center for Devices and Radiological Health has been promoting the development and use of patient registries to advance infrastructure and methodologies for medical device investigation. The FDA 2012 document, “Strengthening the National System for Medical Device Post‐market Surveillance,” highlighted registries as a core foundational infrastructure when linked to other complementary data sources, including embedded unique device identification. The Vascular Quality Initiative (VQI) thoracic endovascular aortic repair for type B aortic dissection project is an innovative method of using quality improvement registries to meet the needs of device evaluation after market approval. Here we report the organization and background of this project and highlight the innovation facilitated by collaboration of physicians, the FDA, and device manufacturers. Methods: This effort used an existing national network of VQI participants to capture patients undergoing thoracic endovascular aortic repair for acute type B aortic dissection within a registry that aligns with standard practice and existing quality efforts. The VQI captures detailed patient, device, and procedural data for consecutive eligible cases under the auspices of a Patient Safety Organization (PSO). Patients were divided into a 5‐year follow‐up group (200 acute; 200 chronic dissections) and a 1‐year follow‐up group (100 acute; 100 chronic). The 5‐year cohort required additional imaging details, and the 1‐year group required standard VQI registry data entry. Results: The sample size of patients in each of the 5‐year acute and chronic dissection arms was achieved ≤24 months of project initiation, and data capture for the 1‐year follow‐up group is also nearly complete. Data completeness and follow‐up has been excellent, and the two FDA‐approved devices for dissection are equally represented. Conclusions: Although the completeness of long‐term follow‐up is yet to be determined, the rapidity of data collection supports the use of this construct for device assessment after market approval. The alignment of this effort with routine clinical practice and ongoing quality improvement initiatives is critical and has required minimal additional effort by practitioners, thus facilitating patient inclusion. Importantly, the success and development of this unique project has helped inform FDA strategy for future device evaluation after market approval.

Clinical Perspective—Early Feasibility Device Medical Studies in the United States: Time for More Than Regulatory Reform

![Figure][1] Everyone complains about the weather but no one does anything about it. The problem of outsourcing of early development and evaluation of medical devices has been like the weather; everyone complains but little has been done. What follows is a call to action to engage all of us

Food and Drug Administration commentary on the SVS masterfile for acute complicated type B aortic dissections and transections

b m d Building on the initial work by Nienaber and Dake, the use of endovascular grafts for the treatment of type B aortic dissections and transections has practically become the standard of care over the last decade. Despite their widespread use, no currently approved endovascular graft in the United States has an indication in the product labeling for treatment of aortic dissection or transection. It would be of great benefit to patients and physicians to develop scientifically valid safety and effectiveness data to support endovascular treatment of aortic dissections and transections as Food and Drug Administration (FDA)approved indications for use. Optimally, data collected from controlled clinical studies would be available to support such new indications. However, completion of randomized trials, or enrollment of concurrent surgical control populations, is likely not feasible for aortic dissections or transactions due to their relatively low incidence. In addition, randomization is not feasible given a lack of clinical equipoise with open surgical repair. Because of these challenges in conducting controlled clinical studies, the FDA has become open to considering single-arm studies for endovascular treatment of aortic dissections and transections.

Regulatory Pathway for Physician-Sponsored Studies Evaluating Endovascular Aortic Repair

Physician-sponsored studies (sponsor-investigator studies) have provided a unique mechanism for advancing the management of complex aortic anatomies. These studies capture data on a relatively broad population with treatment involving cutting edge devices and techniques. Information from these studies can be used to refine patient selection, device designs, operative techniques, risk mitigation strategies, and clinical study endpoints that can be incorporated into manufacturer-sponsored studies. In the US, the Investigational Device Exemptions (IDE) regulations apply to clinical investigations of medical devices. An approved IDE allows for a device to be used for an investigation without complying with many requirements of the Food, Drug, and Cosmetic Act that apply to devices in commercial distribution, for example, needing an approved premarket approval (PMA) application or following the Quality System (QS) Regulation (i.e., with the exception of the design control requirements). This chapter provides an overview of the applicability of the IDE regulations to physician-sponsored studies, and provides insights on the processes for IDE preparation, application, and conduct, based on experience with this type of endovascular graft IDE. The intent of this chapter is to: (1) explain when an IDE is needed; (2) assist in the preparation and submission of an IDE application; and (3) clarify the responsibilities of IDE sponsors-investigators. The intent of this chapter is not to provide regulatory guidance, but rather, to identify lessons learned and helpful tools from successfully implemented physician-sponsored IDEs.