Edwards’s Sapien Trial Raises Bias Question Among FDA Staff

The way Edwards Lifesciences Corp. selected and categorized patients in a trial for its Sapien heart valve may have been biased, making an evaluation of the device as an alternative to open-heart surgery difficult, U.S. Food and Drug Administration staff said.

The transcatheter heart valve, which can be implanted with minimal incisions, worked as well as an operation yet showed higher rates of strokes in the study, the staff said in a report posted online today. The staff said inconsistency in the trial “makes evaluation of these endpoint results difficult.”

“Therefore, the FDA believes that continued long-term follow-up is warranted in a post-approval study should this device be approved,” the staff wrote.

Advisers to the FDA meet June 13 to decide whether Sapien, currently used on heart patients who don’t qualify for surgery, should get expanded approval for people who are high-risk yet capable of handling an operation. The transcatheter valve market may total $2.5 billion in the U.S., said Jason Mills, a San Francisco-based analyst with Canaccord Adams Inc., said.

Edwards fell 0.3 percent to $88 at the close of trading.

The initial FDA approval of Sapien in November boosted Edwards’s transcatheter valve sales 67 percent in the first quarter to $122 million, Michael Mussallem, chairman and chief executive officer of the Irvine, California-based company, said in an April 24 earnings call.

Patient Imbalance

The device is meant to treat aortic senosis. The debilitating condition is caused by a narrowing valve that restricts the ability of blood to enter the aorta, the main artery that carries blood from the heart, according to the National Institutes of Health.

FDA staff said a large imbalance of people in the surgery group withdrew from the trial or died before the procedure, creating the potential for selection bias. Categorizing of patients who were eligible for surgery versus those who weren’t at different trial sites also appeared to vary and 30 percent of patient enrollment was by researchers who had a financial conflict of interest, FDA staff said.

Stroke Risk

Patients who used Sapien experienced double the stroke risk in the first 30 days after the implant procedure, compared with those who had open-heart surgery, FDA staff said. The stroke rate was increased through the year of follow-up for patients who received the device through an incision in the chest compared to those who had Sapien implanted using an incision in the leg. Early research found Sapien caused more strokes in patients after a year than surgery, yet after another year stroke rates evened out, according to Edwards.

Edwards proposed a post-approval study to follow patients in the trial and creating a registry for new patients, according to the FDA. Agency staff said the patients already in the trial should be followed for at least five years.

The Centers for Medicare and Medicaid Services, which oversees health-care plans for the poor, disabled and elderly, said May 1 it would pay for the surgery to insert the valve provided at least two cardiac surgeons evaluate the patient and determine the procedure is appropriate.

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