The FDA’s Circulatory Systems Devices Panel is scheduled to meet June 13 to discuss the safety and efficacy of Edwards Lifesciences' Sapien Heart Valve System. In preparation for the meeting, the FDA has posed a series of questions for panel members to consider.

The FDA approved use of the Sapien transcatheter heart valve for the treatment of inoperable patients with severe symptomatic aortic stenosis in November 2011. In April 2011, Edwards applied for a premarket approval of the device for treatment of patients with severe, symptomatic aortic stenosis who are at high risk for surgery.

In its documents, the agency summarized for reviewers results for the PARTNER trial and provided guidance as they weigh the evidence for benefits and risks.

"The PARTNER trial met the pre-specified criteria for study success, as defined by the primary safety and effectiveness endpoint of all-cause mortality throughout the duration of the study, demonstrating non-inferiority of the Sapien THV (transcatheter heart valve) as compared to the control group," the FDA wrote in its executive summary.

"Throughout the sponsor’s executive summary/briefing book, statements are made for various complications, such as stroke, that 'no statistical differences were observed,'" the agency continued. "These analyses were not pre-specified and/or did not have alpha allocated, and therefore, any p-values associated with these analyses should be interpreted with caution."

Among questions the FDA asked reviewers to consider are:

• Whether refinements are warranted for the indications statement, if approved;
• Whether the device should be considered clinically equivalent to aortic valve replacement; and
• Whether, based on clinical trial findings, a claim can be made for improved survival in the Sapien group.

The FDA asked the panel to consider a variety of safety questions ranging from stroke rates, vascular complications and other clinical issues, including whether the anticoagulation and antiplatelet regimen of the device is sufficiently understood. The panel also has been tasked with looking at the long-term durability of the valve system and the need for a more detailed patient consent.

"The patients in this study were followed for two years but there is limited longer-term data to assess valve durability," the agency wrote.

The panel will focus on the device’s benefits and risks to determine if premarket data meet the threshold for assuring the device is safe and effective. The panel also may deliberate about potential post-approval studies.

"While not impacting the primary hypothesis testing for the PARTNER trial," the panel wrote, "the limited longer-term data available for this novel device and procedure supports the need for robust post-approval follow-up to bolster our understanding of device durability and longer-term performance if the device is approved."