As doctors and medical device manufacturers embrace the brave new world of using implanted stimulators to regulate organs, mood, and appetite, critics charge that the Food and Drug Administration is failing to guarantee that such implants work as advertised. Senator Charles Grassley (R-Iowa), who led the investigations into the FDA's monitoring of Vioxx and other drugs, is currently exploring the agency's oversight of implants and other medical devices.
Even relatively noncontroversial implants like heart defibrillators are under fire. Since 2000, their use has tripled, and recent changes to Medicare reimbursement rules have further expanded the pool of potential patients. Critics charge that defibrillators are already being implanted in patients either too healthy or too sick to be good candidates. Meanwhile, it was recently revealed that Guidant Corporation failed for three years to disclose that its Ventak Prizm 2 defibrillator had a defect that could cause it to short-circuit. Only when the New York Times was about to expose the problem and related deaths did Guidant issue an alert to doctors and patients. It has since recalled more than 20 models of pacemakers. Asked to provide defibrillator failure reports, the FDA sent out heavily redacted documents, calling the censored data a corporate "trade secret."
When it comes to implants designed to treat mental illness, the concerns go way beyond mechanical malfunction. Brain implants—such as those made by Medtronic and used on Mario—are still only experimental for psychiatric problems (although they've been used to treat seizures and motion disorders for years). But in July, Cyberonics received FDA approval for its Vagus Nerve Stimulation (VNS) neck implant to treat depression in adults who haven't responded to four or more other forms of treatment, such as antidepressants and electroconvulsive therapy. (Though, as always, it's up to doctors to abide by those guidelines.)
Originally conceived to treat epilepsy, VNS devices, which send a current up the vagus nerve and into the brain, have been approved for use on treatment-resistant depression in both Europe and Canada since 2001. However, the main U.S. clinical trial found that after three months there was no statistical difference in improvement
between VNS patients and those in the control group who had the devices put in but not turned on. Furthermore, some VNS patients have seen their depression deepen—20 attempted suicide. Nevertheless, in June 2004 an FDA advisory committee voted 5-2 to approve VNS. Committee members said they were moved by profoundly depressed patients who'd failed to respond to other therapies, and anything that could provide them hope is "potentially worthwhile."
Two months later, however, the FDA deemed the device "not approvable." Cyberonics appealed, stressing that after two years, 18 percent of VNS patients "were depression free" and 57 percent saw "at least a meaningful clinical benefit." (An FDA reviewer found the methodology used to glean these results "highly questionable.") Despite an ongoing investigation into the Cyberonics application process by Grassley's
committee, FDA approval came in July, though only after the head of the FDA's device center, Dr. Daniel Schultz, overruled the review division.
Public Citizen's Dr. Peter Lurie called the approval one of the FDA's "most questionable regulatory decisions," an example of "data-free decision making," and evidence that the standard of approval for medical devices—that is, a "reasonable assurance of safety and effectiveness"—should be raised to the "safe and effective" standard of drugs. For its part, Cyberonics has hired hundreds of salespeople to chase after the 4 million treatment-resistant depressives that the company says represent a $200 million market—$1 billion by 2010. As Medtronic and other implant makers struggle to catch up, Cyberonics is pushing to get approval to use its VNS device to treat everything from Alzheimer's to chronic headaches. The brain represents the next frontier for medical devices, CEO Skip Cummins says, and will attract the kind of extensive R&D that the cardiac-rhythm business saw in the 1960s.
Let's just hope the regulators keep up with the times.