At a time when many of Europe’s medical technology markets are effectively going backwards due to complications created by the EU Medical Device Regulation (MDR), corresponding sectors in the USA are receiving an inevitable boost. Alongside the US Food and Drug Administration (FDA), the country’s leading clinicians and industry figures have seized this opportunity—and, thanks to the Early Feasibility Study (EFS) programme, can now potentially play a leading role in advancing novel devices within the neurovascular space.
According to Chip Hance, Regatta Medical CEO and a member of the Medical Device Innovation Consortium (MDIC) board of directors, the EFS programme was conceptualised back in 2013 after the FDA released a guidance document on the need to improve domestic innovation in the USA. Hance recalls that the catalyst for this was observed in the structural heart sector. A decade ago, the USA became the 43rd country, globally, in which the first transcatheter aortic valve implantation (TAVI) device gained regulatory approval; an occurrence Hance states is widely noted, and one that led the FDA to highlight the need for an optimised pathway allowing device developers to conduct early-feasibility research before gaining finalised US approval.
Owing to the successes that followed in interventional cardiology, other spaces soon took an interest. But, as Hance points out, real advancement requires an “enthusiastic clinical champion” to begin with—a mantle he attributes to neurosurgeon Adnan Siddiqui (University of Buffalo/Jacobs Institute, Buffalo, USA), who saw what was happening in structural heart around 2019 and recognised the impact it could have in neurovascular technologies as well.
“Necessity was the mother of invention,” Siddiqui tells NeuroNews, noting that, traditionally, the “vast majority” of endovascular devices created in the USA would be commercialised and enter clinical use across much of the rest of the world while US physicians were still awaiting availability. “This was routine, and so people like Chip and organisations like the MDIC went to the FDA to try to change that narrative,” he continues. “In the absence of an EFS programme, companies developing innovative therapies do not have a tenable pathway for approval in the USA. Through collaboration of stakeholders working under the MDIC umbrella, the USA has become a competitive environment for early innovation.”
Importance of the EFS programme
Early-feasibility studies are often a “choke” in making novel technologies available to patients, Hance states, as they are just one aspect of the regulatory process but can take a year or more, in many cases, to navigate.
“We have been on a mission for six or seven years to try and streamline the process, getting sites [on board] that have the experience to actually do these kinds of studies, and what I think it ultimately does is help get novel, game-changing therapies to patients in the USA,” he says. “We can talk about EFS, and contracting, and all of the mechanical aspects, but really it is about getting novel therapies to patients more quickly.”
Here, Siddiqui weighs in, noting that, while the FDA’s original 2013 publication of EFS guidance helped companies get through the agency’s actual review process fairly quickly, other elements—including engagement of clinical study sites and patient enrolment—kept early-stage research moving at a “very slow” pace overall. Clinical, regulatory and industry leaders turned to MDIC, a public-private partnership seeking to optimise medical technology innovation, to “shepherd this ecosystem forward”—initially in structural heart, but more recently in electrophysiology and, of course, stroke care.
The MDIC does this in numerous different ways, leveraging the expertise and experience of its members to support device developers with contracting, informed consent, legal documentation, best-practices guidance and more via its online toolkit. This, in combination with continuously tracking EFS performance metrics, is ultimately intended to drive overall EFS efficiency and effectiveness for US patients. According to Hance, a big part of the MDIC’s role here is to identify sites like Siddiqui’s in Buffalo that not only have the clinical know-how to host a successful, rigorous EFS, but also the structures and processes to conduct these studies in an efficient fashion.
While these endeavours have been “slowly but surely” moving forward within the neurovascular sphere over the past 12 months, Siddiqui believes “this has the potential to truly transform how technologies that are being imagined, developed and incorporated in the USA can benefit our patients first”. Highlighting the interest he has observed thus far, he references dedicated EFS symposia that have taken place at the past couple of Society of NeuroInterventional Surgery (SNIS) meetings, as well as “very well-attended” breakfast seminars allowing companies to get involved—noting “we have run out of chairs in the room”—and claims an “even bigger footprint” is expected at upcoming neurovascular conferences.
“I think the entire neuro community is really glad to see this initiative, and it is certainly not limited to start-ups—three of our EFS’ are with Medtronic,” Siddiqui adds.
Neurovascular success stories
Having recovered from an initial three-month dead stop in 2021, brought on by the COVID-19 pandemic, early-stage neurovascular research in the USA is now reaping rewards from the years of graft that helped establish the EFS programme. One example Siddiqui points to is that of Cerevasc’s eShunt device for treating hydrocephalus, which is implanted via an incisionless procedure rather than more traditional open surgery—a “brilliant” idea, he posits, recalling that he wanted the company’s CEO Dan Levangie to conduct first-in-human studies with the technology in the USA.
Instead, they went with Pedro Lylyk (Buenos Aires, Argentina)—a neurosurgical pioneer who has led numerous investigative studies in this space. However, while Cerevasc initially planned to remain in Argentina following this, the allure created by the FDA’s new EFS pathway led Levangie and co to return to the USA for its subsequent feasibility studies. This research is ongoing, with Yale University (New Haven, USA) having performed some cases and Siddiqui’s own centre set to conduct a handful in the near future too.
“Another example is Synchron, with the Stentrode brain-computer interface,” he goes on. “Same concept; Australian company, but based out of Brooklyn, [and we] wanted them to do first-in-human studies in the USA. And, again, their initial instinct was to start in Australia. They did four cases out there, but then they got really interested in EFS, enquired, and now we have an EFS in the USA with two patients enrolled at Mount Sinai [New York City, USA] and one coming up here [to Buffalo].
“So, I saw these two companies pivot, in real time, from OUS to US, only because we have an EFS pathway, and I am really excited about these two radically different things—one is an [endovascular] brain-computer interface, never done before, and the other is an endovascular hydrocephalus treatment, also never done before.”
While Cerevasc and Synchron are relatively small companies at the cutting-edge of current neurovascular innovation, Siddiqui suggests that iterative technologies can also benefit. For example, next-generation stent retrievers like Medtronic’s Delphi revascularisation device are currently being assessed via EFS’, as are newer flow diverters and detachable coils, including Stryker’s Citadel embolisation device for intracranial aneurysms.
Siddiqui feels that—provided companies are willing to engage with the FDA early on—starting with an EFS is becoming an increasingly smooth process whereby device developers can “seamlessly” transition into one of several other regulatory stages: a humanitarian device exemption (HDE) pathway, 510(k) clearance or premarket approval (PMA) application.
Across the Atlantic
Hance and Siddiqui are in agreement that the challenges of implementing EU MDR has drawn new attention to the US EFS pathway—particularly when it comes to the implantables and other Class III devices constituting most novel therapies in the structural heart and neurovascular worlds.
According to Hance, European companies are re-thinking their clinical strategies due to these regulatory challenges and have seen less activity in medical technology innovation. When asked if there are any other geographies that can rival the early-feasibility processes established by the FDA and supported by MDIC in the USA, Siddiqui notes that there is a similar process in Japan, but avers that it is “not well coordinated” by the country’s regulatory agency, with research endeavours often being “much more ad hoc” than the organised, collective ‘ecosystem’ the USA now boasts as a result.
Having worked in the neurovascular space early on in his career, Hance recalls that, previously, companies would never share their supposed ‘best practices’, so as not to cede an advantage to their competitors.
“I remember finally getting exposed to other companies and realising: ‘we all think we are better than everybody else, but we are all wrestling with the same issues.’ So, the only way we are going to get better [at it] is to break down the barriers between ourselves; share what works well; and get a better, healthier ecosystem in which to conduct efficient clinical research,” Hance continues.
Looking to the future, Siddiqui concedes that—while EFS is “unique”, globally, in that the FDA is engaged “from day one”—there are still certain things that need to be ironed out, such as reimbursement policies and coverage analysis for innovative technologies and investigational devices.
“One of the reasons for our success has been the standardisation of the EFS pathway,” Siddiqui concludes. “It has actually led to a lot of companies, including European companies, coming to the USA for a first clinical site.”