CDU Washington Editor

WASHINGTON – As attendees at the 16th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium here in late September examined trial results and the latest trends in medical device technology, there also was an eye on the big picture and how innovation affects healthcare as a whole.

Dean Kereiakes, MD, professor of clinical medicine at Ohio State University (Columbus) and CEO and director of research at the Ohio Heart Health Center (Cincinnati), made a presentation called the "Societal Impact of a Transforming Medical Technology: A Drug-Eluting Stent Case Study."

Kereiakes cited the "revolution" in stent technology to illustrate how healthcare research is on the verge of several advancements. But the tone of his presentation was critical of the regulatory process in the U.S., and he received aggressive push-back from Bram Zuckerman, MD, director of the director of the division of cardiovascular devices at the FDA's Center for Devices and Radiological Health, who defended the agency's deliberative approach.

Kereiakes said, "By 2015, cystic fibrosis and other single-gene defects may be cured. By 2040, the prophesy of a cure for cancer and heart disease could be a reality. Transformational technology should change the current standard of practice and should have wide-based applicability."

He cited implantable defibrillators and drug-eluting stents as clear examples of this transformational type of technology. "Angiographic restenosis was reduced by almost 50% compared to angioplasty," he said. "We saw an 80% reduction in angiographic restenosis [with drug-eluting stents] compared to the bare-metal stent."

Though citing the numerous benefits from these transformational technologies, Kereiakes characterized the road to end use as "a long, arduous and expensive task." Companies may get through development and approval, but then have to tackle reimbursement issues, he cautioned.

"The differences in the clinical and regulatory environments in the U.S. and Europe help explain why much early device testing takes place outside the U.S. and why introduction of new devices into clinical practice is usually significantly delayed – up to three years – in the U.S. compared to Europe," he said.

He added: "At this meeting in 2002, David Feigal [then head of the CDRH] projected that there would be at least a 2 1/2-year time delay from CE mark to FDA approval in 2004. The Feigal prophesy has proven true."

Kereiakes said post-market surveillance must be used to "expedite and facilitate" premarket approval and hopefully would provide good efficacy for expanding patient education.

He also raised an issue key to the current political debates: "Is U.S. healthcare an entitlement of a privilege? The number of uninsured has continued to rise over the past 15 years, and the uninsured are seven times more likely not to get the care they need for a serious medical condition, which limits access to a transformational technology."

The other issue Kereiakes tackled in his presentation was reimbursement. He said the U.S. is "poised for a paradigm shift" in reimbursement because the system "does not adequately provide for the American people." And he charged that the current system enables wide discrepancies in reimbursement for the same diagnosis-related coding groups. "Drug-eluting stents vary from $1,800 to $4,300 depending on geographic location. And there remains no incremental reimbursement for multi-vessel revascularization yet on the horizon," he said.

Interventions and innovations should be judged not only on the basis of physical costs but also in terms of value as measured by the healthcare system, patients and societal perspectives, Kereiakes argued. "This dictates that we consider healthcare as an investment and evaluate products and services in terms of their return on investment." He concluded: "Payers, investigators, regulators, inventors – all stakeholders in this process represented here today – have an obligation to the American public to provide timely access to leading edge technology."

Immediately following Kereiakes, Zuckerman fired back with the FDA perspective. "Dr. Kereiakes has given a visionary presentation on where medical technology should go," Zuckerman said. "But let me provide some other examples."

He said the FDA has a unique regulatory perspective for device-transforming technology, with the goal of establishing safety and effectiveness for device submissions. "The role of the FDA is unique around the world," Zuckerman said. "No other regulatory agency has the mandate that we have. It is reasonable and not absolute. But we have to understand what safety and effectiveness are."

He said manufacturers must show that a positive risk/ benefit analysis demonstrates clinical utility, and that is a unique regulatory requirement for the U.S. compared to Europe. "There are some basic issues that easily come across when trying to understand the differences between the U.S. and the rest of the world toward life-transforming technologies," Zuckerman said.

Perhaps the best question, he said, is whether or not to randomize clinical trial data. "Certainly the agency listens very closely to different sorts of trial designs that are not randomized, and there are some good reasons for considering an unrandomized trial," he said. "On the other hand, one needs to recognize the science of looking at [how] non-randomized data has improved over the last decade."

Zuckerman likened the use of non-randomized data to an apples and oranges comparison, adding, "I hope you can appreciate that the agency needs to compare apples to apples. Given our mandate, we are interested in key clinical endpoints." He called Kereiakes' proposal to use post-market surveillance for pre-approval requirements an "interesting hypothesis," but said that a "pace lag" between the U.S. and Europe wasn't necessarily a bad thing.

"The agency is well aware of the iterative device development process where we go rapidly from one generation to the next," he said. "On the other hand, we cannot avoid the fact that there needs to be a certain level of evidence required before approval of a medical device in the U.S. That's the law."

Zuckerman said there were "several problems" with post-market surveillance in this country, as well as around the world, that would limit some of the data gathering that Kereakis suggested. "Drug-eluting and carotid stent development is a complex process," he acknowledged, but he said there were processes in place to ensure safety and indicated that to relax those requirements in favor of a possibly speedier process would be reckless.

His conclusion: "I urge manufacturers and industry to maintain dialog with the agency to streamline the process."