CardioExchange Archive

In a startling break with tradition, the American College of Cardiology (ACC) and the Society of Thoracic Surgeons (STS) will manage and run their own clinical trials testing expanded uses for transcatheter aortic valve replacement (TAVR). The two medical groups have recently been granted an investigational device exemption (IDE) by the FDA for one such trial and hope to gain an IDE for at least two more trials. The news was first reported by The Gray Sheet (subscription required) on February 8.

The new development represents a significant enlargement of the TVT registry, already run by the ACC and STS, which tracks all TAVR usage in the U.S. At the request of the FDA, the TVT registry was developed, according to STS former president Michael Mack, in response to “the total dissatisfaction felt by all stakeholders” over the problems engendered by a dysfunctional postmarket surveillance system. The TVT registry was then started so that U.S. physicians and hospitals could comply with Medicare’s National Coverage Decision (NCD) for TAVR. The NCD itself was originally proposed by the ACC and STS in response to concerns over the potential problems and confusion that a disruptive new technology like TAVR could unleash. The NCD ensures Medicare reimbursement for FDA-approved uses of TAVR.

But the NCD also contained a specific provision that prevented reimbursement for off-label uses unless patients were enrolled in clinical trials. At the time, none of the organizations — Edwards Lifesciences (manufacturer of the Sapien device), FDA, CMS, ACC, and STS —  imagined that the ACC and STS would end up seeking an IDE as a result of this provision. Said Mack: “this was an unintended consequence of the way the NCD came out. We weren’t smart enough to anticipate this, that by applying for the NCD, we were getting into the IDE business.”

Ralph Brindis, a former president of the ACC, explained that as physicians became familiar with TAVR they grew interested in exploring off-label uses of the device. The new trials will mean that reimbursement will now be possible for some of these uses when patients are enrolled in the clinical trials. According to Mack, the NCD “took off-label use off the table. If you are a cynic this is good, but if you’re a practitioner this is tying your hands.”

“This is the first time the societies have ever filed for an investigational device exemption,” said Brindis. “The goal of the effort is to gain reimbursement for an expanded set of procedures with Sapien to make the device accessible to more patients.”

The first trial will study alternatives to transfemoral approaches in 1,000 patients considered ineligible for aortic valve surgery. “Since transapical and transaortic [approaches] were not studied in the inoperable patient population, they aren’t covered,” Michael Mack told The Gray Sheet. “The only way to get them covered is by getting an FDA label. How do you get an FDA label — you have to get approval by an investigational device exemption study.”

Brindis and Mack said that the ACC and STS worked closely with CMS, the FDA, and Edwards Lifesciences to develop the trial protocol. In the trial, patients not eligible for aortic valve surgery will receive TAVR through transapical and transaortic approaches and will be compared with the results of patients in the original PARTNER A trial who received TAVR through the transapical approach. Mack concedes that the trial design is not ideal. “There is no perfect comparator,” he acknowledged.

Other experts in the field contacted by CardioExchange agreed that the challenges of trial design in this situation are quite formidable. Randomized trials are not always feasible and, in some situations, may be unethical. The IDE is an attempt to balance the need for rational clinical trials, on the one hand, and the growing pressure to perform off-label procedures. It should be noted that an important safeguard for patients remains in place: all potential TAVR patients will still need to be evaluated by both a cardiologist and a cardiac surgeon as part of the “heart team” approach mandated by the FDA and the NCD. (See my previous post, Politics and Transcatheter Aortic Valve Replacement, for more background and discussion about the introduction of TAVR in the U.S.)

The ACC and STS are now working to gain FDA approval to perform two more studies. One would examine the role of alternative approaches in the high-risk population eligible for surgery. The second would study valve-in-valve TAVR procedures. Both studies also present challenging problems of trial design. Mack said he anticipates FDA approval of these protocols in the next few months.

Edwards Lifesciences has played a quiet role in these proceedings so far. According to Brindis and Mack, Edwards has helped support the ACC and STS effort. Now that supporting role is scheduled to grow: on Monday, Brindis said, Edwards agreed in principle to fund the clinical trials. An Edwards representative confirmed that the company planned to support these new trials, but the details have not yet been hammered out.