An Interview With Rodney White, MD
One of the world’s foremost endovascular device experts discusses the reasons for the remarkable success of a relatively new technology and the promise it holds.
Please tell us about your early work in developing stent grafts. We began in the early 1990s with animal experiments looking at the combination of conventional graft materials and balloon-expandable Palmaz stents. Our goal was to see if we could deploy them using low-profile catheters and if they would heal. This early work led to our receiving the first FDA-approved investigator-sponsored Investigational Device Exemption (IDE) for evaluating hand-made endoluminal grafts for aneurysm exclusion. This was stimulated by the pioneering work of Drs. Juan Parodi and Julio Palmaz, who had helped us in the initial phases of this study. Commercial prototypes quickly followed and we were fortunate to work with Dr. Tom Fogarty in the initial animal and clinical AneuRx trials, in which I was the US study’s PI. Subsequent work with many additional devices in both the laboratory and clinical studies sets the stage for our current interest and activity in this field.
You’ve been very involved with the Lifeline Registry. What kind of work do you with that organization? I’m chairman of the Endovascular Aneurysm Registry Committee sponsored by the Lifeline Foundation of the Society for Vascular Surgery. The Registry has developed clinical data collection protocols through the efforts of key experts and independent consultants to address the introduction and development of new EVAR technologies. The Registry was initiated through a collaboration involving clinical investigators, the medical device manufacturers, and representatives of both the FDA and CMS. The Registry offers two unique data reporting options: (1) long-term follow-up surveillance fulfilling manufacturers postmarket approval requirement on patients presented in PMA studies at the time of FDA approval, and (2) a clinical registry for commercial devices implanted following FDA approval, and for devices being implanted as part of FDA-approved investigator IDEs. The PMA cohort currently consists of approximately 1,800 patients with 3- to 7-year follow up. An additional 500 to 700 patients from other PMA studies are anticipated in the near future, as are several hundred conventional surgery control patients. In light of the high compliance reporting rate (approximately 80%) for this data, as it represents the information from mandated FDA reports, the information is a uniquely valuable source on the performance of currently approved AAA endograft devices.
How will the long-term follow-up impact on patient care? If the data are collected appropriately—with a high level of compliance and accuracy—it will not only improve patient care, it could provide information leading to the development of better, faster, more appropriate technologies in problem areas. We hope that it will provide a data set on pre- and postmarket patients like Eurostar has attempted to do in Europe. A newly developed program of the Registry is to offer a surveillance and reporting mechanism for commercial patients receiving devices following FDA approval, and for FDA-approved investigator IDEs for AAA and TAA. Physicians and hospitals adopting EVAR are being confronted by an escalating need to develop cost-effective, reliable means to not only select appropriate patients, but provide postimplant surveillance. A postmarket study conducted by the Lifeline Registry is analyzing a method of providing reliable electronic storage of data that would fulfill not only the clinical need for rapid, accessible, and reliable data for sequential patient visits, but also potentially make these data available for electronic transmission, if needed. The surveillance concept is applicable to all patients with endoluminal devices and has been found to be very helpful in identifying patient variables that enhance successful selection of patients for the procedures. The global benefits of a cost-effective registry and surveillance program not only promote a more rapid and appropriate development of the technology, but also enhance appropriate patient selection and ensure recognition of problems requiring intervention.
You’re one of the most active physicians in the country when it comes to FDA clinical trials. What is your perspective on the current state of device regulation in the US? Significant progress has been made regarding device regulation, with manufacturers and agencies looking for methods to provide improved devices in a cost-effective and efficient manner. In the past, there has been some distance and occasional mistrust between the agencies and the manufacturers. Part of what has occurred, as the result of a good faith effort on the part of the FDA and CMS, is an attempt to maintain safety while making trials faster and more cost-efficient, with a shortening of the time interval between device approval and funding.
Take, for example, endoluminal devices, which are used in a very high-risk cardiovascular population with significant morbidity and mortality, with the mid-term follow-up data showing that patients are doing remarkably well. For a first-time technology in a high-risk population with a high level of surveillance, the development of those devices is impressive. If you think back to when cardiovascular surgery developed 50 years ago, when surgeons were putting vascular grafts in a very high-risk population, it was an unusual situation if a patient survived. There have been substantial improvements since then, but considering the degree to which device development and sophistication have improved over a relatively short interval, it’s actually more than I think some would have imagined.
A second example in which the FDA and CMS have collaborated with industry and investigators to address device development and evaluation is in the CARESS trial. CARESS is an FDA-approved IDE sponsored by the International Society for Endovascular Specialists (ISES). The study offers a new mechanism for multiple manufacturers to potentially gain approval under one IDE. The CARESS phase I data, which were recently presented at the AHA meeting and will soon be published in the Journal of Endovascular Therapy, are unique in that this is the first study that suggests that carotid stent systems (CSS) (ie, a stent plus protection) may provide outcomes comparable to conventional carotid endarterectomy (CEA) in a population that represents the current indications for CEA intervention.
The CARESS study involved the prospective, concurrent entry of all patients meeting convention criterion for CEA in a clinical practice referral model. The study involved approximately 250 CEA and 150 CSS patients with 70% of patients being asymptomatic. The 30-day stroke and mortality in both arms of the study were 2%, representing the first study that addresses the broad clinical population where approved stent technologies may be used. As PI of the CARESS study and Past President of ISES, I can say that the collaboration of the agencies (FDA and CMS), the manufacturers sponsoring the phase I trial (Boston Scientific and Medtronic), and the investigational sites have proven the utility of this potential new model, and is a tangible demonstration of the agencies’ willingness to address new ways to expediently evaluate new patient treatment options.
Although you hear a lot of pessimistic arguments about agencies being in the way and device development being stalled, all parties involved are doing their best to try to get it to move quickly and efficiently.
As someone who has worked extensively with a variety of stenting devices, what are your thoughts on short-term versus long-term fixation and tissue incorporation in cardiovascular devices? In the thoracoabdominal aorta and iliac arteries, convention polyester and Teflon vascular prosthetic materials become incorporated with fibrous tissue and fibrohistiocytic cellular components when exposed to viable cells in the arterial wall. The bond that is formed is not strong enough to support long-term fixation unless sutures secure anastomoses in conventional repairs, or if the graft is secured to the vascular wall by a stent or other wire or fine mesh metallic or polymeric lattice. The early work of Drs. Parodi and Palmaz demonstrated fixation by means of incorporation of the stent structure. Ongoing assessment of current devices should include explant analysis to observe the long-term incorporation. Acute fixation can be accomplished by several mechanisms including oversizing of expandable stents combined with column strength of the device, fixation with hooks or barbs, or suprarenal components. Long-term incorporation is independent of the acute fixation methods and depends on the tissue incorporation of the metallic components.
As an example, several explant analyses of AneuRx devices demonstrates that the external stents attached to the outside of the device become incorporated with mature fibrous tissue over the first few months following implantation and provides a means for long-term fixation. One requirement is that the device is appropriately sized and accurately deployed in aortic and iliac artery fixation sites that have viable tissue apposition. Dr. Fogarty’s original hypothesis that the external stent structure would support viable fixation has been confirmed by these observations and provides an important clinical correlation for future device design. Long-term analysis of other types of devices is required to determine the type and degree of fixation so that this critical database can be expanded. The Lifeline Registry has also developed an explant program that is designed to expedite explant retrieval and analysis.