GAITHERSBURG, MD. — The AbioCor total artificial heart did not meet the Food and Drug Administration's humanitarian-device exemption requirements, according to the FDA's Circulatory Systems Devices Panel. The vote was 7–6 against, with one abstention.
The committee determined that the device maker Abiomed's submission under the humanitarian-device exemption standards was inadequate. Concerns were based on undefined anticoagulation treatment protocols and the lack of quality of life data. The panel stressed the need for more extensive studies demonstrating the device's safety.
The AbioCor Implantable Replacement Heart is the first fully implantable artificial heart for severe end-stage heart failure patients who are younger than 75 years, not transplant candidates at the time of assessment, and in biventricular failure not treatable by a destination-therapy left ventricular-assist device. The device is designated as a last resort for a small patient population with a poor prognosis of survival within 30 days.
Abiomed submitted data from a clinical trial spanning slightly more than 3 years, from 2001 through 2004. The device was implanted into a total of 14 patients. The trial was initially designed to assess patient survival at 2 months.
Two patients died during implantation, and two others died before the 60-day end point. Three of the patients who survived more than 60 days had strokes prior to 60 days. A device failed in one patient at 5 months, and in another patient, the device wore out expectedly at 17 months. (The average runtime during bench tests was 18.8 months.) Complications included postoperative bleeding requiring reoperation and neurologic events.
Two patients improved enough to be discharged from the hospital—one to the patient's home and the other to a hotel near the hospital.
Although a humanitarian-device exemption is similar in both form and content to an FDA premarket approval application, requiring reasonable assurance of safety and probable benefit, it is exempt from the effectiveness requirements of a premarket approval. The sponsor's representatives stressed this distinction during their presentations to the panel and emphasized the groundbreaking nature of the technology. The FDA's presentation to the panel offered a somewhat mixed evaluation of the device. Biomedical engineer Eric Chen, the FDA's lead reviewer, asserted that the device met the humanitarian device exemption's requisite standards for biocompatibility, electrical safety, and manufacturing, but he said there are still concerns about reliability. Julie Swain, M.D., leading the FDA's clinical review team, said “This device is a real dilemma.” She asserted that the relationship between risk and benefit was very difficult to ascertain, “due to a lack of validated quality of life and functional data.”
Discussion among panel members echoed the uncertainties of the FDA review team. Joanne Lindenfeld, M.D., director of heart transplantation at the University of Colorado, Denver, said, “Safety is the biggest concern here. We see enormous [incidence of] death due to stroke.” Dr. Lindenfeld said that she could not support the device because she was “unconvinced that we've settled the issue of bleeding and stroke.” Thomas B. Ferguson, M.D., of Washington University, St. Louis, spoke to concerns about anticoagulation, telling the sponsor's representatives that he would “like to be reassured that you are totally convinced that … all has been done to minimize the device as a clot producer.”
The FDA usually follows the recommendations of its advisory panels but is under no statutory obligation to do so.