UPDATED 6/11/2012 2:30 p.m. with comment from Edwards
The watchdog agency’s Circulatory Devices panel is slated to meet June 13 to consider a pre-market approval application for the Sapien transcatheter aortic valve implant to cover high-risk patients.
Edwards won a PMA for the Sapien device for inoperable patients with aortic stenosis, a hardening and narrowing of the aortic valve, in November 2011.* FDA reviewers said the arm of the study covering the high-risk patients may have been flawed by the inconsistencies.
"FDA notes that screening and subsequent enrollment practices were not homogenous. The large variation between the ratios of those screened to those enrolled may represent different selection criteria among sites," according to documents released ahead of the meeting scheduled for Wednesday. "Enrollment practices related to identification of ‘inoperable’ and ‘high risk’ patients were not homogenous across sites."
There was "no significant difference" in mortality between patients treated with surgery vs. treatment with the Sapien valve, according to the documents. But some patients who were slated for traditional open heart surgery were treated with the TAVI device, and vice-versa, making it difficult to evaluate the study’s endpoints.
"[T]he issue of [surgery] patients not receiving [surgery], [Sapien] patients receiving [surgery], and [surgery] patients undergoing concomitant operations makes evaluation of these endpoint results difficult," according to the FDA reviewers. "Although the primary endpoint was met, issues related to potential selection bias confound the interpretation of these results."
“We believe the Partner trial was well-designed and executed. We are proud of the efforts of the leading heart teams that supported this ground-breaking trial and what it means for patients,” an Edwards spokeswoman told MassDevice.com via email. “We are reserving further comment on this or related matters until the Advisory Committee scheduled for June 13.”
The FDA also wants the circulatory devices panel to consider better ways to construct future trials of similar devices and to come up with appropriate endpoints for a post-market surveillance study. The panel is scheduled to vote on whether the device is as safe and effective as surgery and whether its benefits outweigh its risks for the high-risk cohort.
*Correction, June 12, 2011: This article originally stated that Edwards received FDA approval for lower-risk patients last November; that approval was for patients too sick to undergo open heart surgery. Return to the corrected sentence.