WASHINGTON — Early feasibility studies are reviving device innovation in the United States, and offer several clinical advantages, as well as challenges, for interventional cardiologists, according to a speaker at TCT 2016.
“Over the past 2 decades, from the standpoint of access to new device therapies, U.S. interventionalists have been stuck in the mud,” Martin B. Leon, MD, founder and chairman emeritus of the Cardiovascular Research Foundation, said during a presentation. “It’s been frustrating. We’ve been on life support, and, for us, EFS (early feasibility studies) are like a breath of fresh air. It’s really allowed us to get into a completely different space.”
There are clinical advantages for both investigators and sites who want to participate in an EFS, Leon said. Participating investigators receive early access to novel therapies, and can apply their skills and experiences to help iterate new devices and procedures.
“Participation in the evidence development process is exciting,” Leon, professor of medicine at Columbia University Medical Center, director of the Center for Interventional Vascular Therapy, director of the cardiac catheterization laboratories, and a member of the executive board of the Columbia NewYork-Presbyterian Heart Valve Center, and a member of the Cardiology Today’s Intervention Editorial Board, said. “The intellectual curiosity, the opportunity to have an impact on evolving new medical therapies; there is a lot of professional satisfaction related to [participating].”
There are key differences between an early feasibility study and a standard trial, Leon said, and investigators should be prepared to address them.
“When you compare an EFS to a standard study, you have to raise the bar,” Leon said. “It is different, and if you think of it in the same way, then you will fail.”
With an EFS, the Investigational Review Board (IRB) approval process is different, Leon said, and often investigators will receive passive or active opposition to their application due to risk aversion. Informed consent language also has to be different, Leon said, noting that it can be a challenge to address what are often unknown and increased patient risks.
Contract negotiations, including indemnification clauses, liability concerns and site payments, are also different, he said, whereas study reimbursement has been problematic and there has been “relatively poor alignment” with CMS.
EFS studies also require a more experienced, customized team, more intense training and modified procedural practice, he said.
“Sites have to accept, and, I would argue, embrace the reality that EFS are importantly different than standard trials,” Leon said. “If they don’t, they shouldn’t participate.”
Despite challenges, Leon said, the FDA has been responsive and engaged throughout the process, with what he called a “surprising commitment” to the program. The FDA has also proved willing to accept complications in high-risk patients treated with novel devices, and be flexible about device iterations like clinical trial adjustments, he said.
EFS ‘choke points’
Sites, sponsors and other stakeholders, however, have been less prepared, Leon said, in part because there is a lack of understanding regarding the differences between EFS and standard trials.
“This results in what I would describe as ‘initiation angst,’” Leon said. “It’s due to delayed IRB approvals, anxious informed consent discussions, especially these indemnifications and site payment agreements and confusing CMS reimbursement policies. So, patient enrollment has been more complex and unexpectedly erratic.”
Sponsors, too, need to address the site qualification selection process, which is sometimes biased and ineffective, he said.
“Sponsors want their own sites, often without considering what would be a good EFS site,” Leon said.
To address “choke points” in the process, Leon recommended improvements in four key areas: study initiation, patient recruitment, procedure management and study assessment.
IRB approval, he said, should ideally be completed within 1 month, with IRB submissions and contracts reviewed simultaneously. Sponsors should commit to fund non-usual care tests and sites should commit to fulfill reasonable enrollment expectations. An improved patient rights advocacy process throughout the trial process – from informed consent, to index procedure to follow-up – should be uniform and embedded, Leon said, and sites must be willing to form dedicated EFS teams.
“The honeymoon for EFS is over,” Leon said. “Now is the time for a critical re-evaluation of all aspects of the program to determine if EFS can truly revive device innovation in the US, provide early access to novel therapies for our patients and accelerate the device approval process.” – by Regina Schaffer
Leon MB. EFS in the USA: Challenges and Developments. Presented at: TCT Scientific Symposium; Oct. 29-Nov. 2, 2016; Washington.
Leon reports receiving research support, consultant fees or honoraria from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic and St. Jude Medical, and holding equity in Claret, Cathworks, Elixer, GDS, Medinol, Mitralign and Valve Medical.