Medical Device Daily Associate Managing Editor

Watchdog group Public Citizen (Washington) has called for U.S. regulators to pull Cyberonics ' (Houston) depression treatment from the U.S. market, claiming the company has not proven that the electronic stimulator device is effective.

The group urged the Centers for Medicare & Medicaid Services (CMS; Baltimore) not to reimburse for the surgically implanted Vagus Nerve Stimulation (VNS) electronic device in the treatment of severe depression because it charges that the therapy is “ineffective.”

Public Citizen said it is apparently the first advocacy group to seek a National Coverage Determination denying reimbursement under Medicare. The consumer group also is filing a petition with the FDA urging the reversal of its July 2005 approval of VNS for treatment-resistant depression (TRD) (Medical Device Daily, July 19, 2005).

“Without proof that VNS is a viable therapy for severe depression, it is unreasonable for the Medicare program to reimburse for this device,” said Dr. Peter Lurie, deputy director of Public Citizen's Health Research Group. “With substantial constraints on the Medicare budget and so many clear needs going unmet, it seems absurd to flush away millions of dollars on this unproven device.”

The VNS device is implanted beneath a patient's left collar bone in an outpatient procedure that costs about $25,000, including the device itself. The device was first approved for the treatment of severe epilepsy in 1997, but Public Citizen said that Cyberonics pushed for it to be approved for severe depression as well, claiming that the potential severe depression market encompassed 4.4 million people in the U.S. alone. Cyberonics filed a request for national Medicare reimbursement for use of the device to treat severe depression on July 24, but the company has been denied approval for reimbursement from 10 local CMS contractors in 14 states. To date, no contractors have agreed to reimburse for the device.

On the private side, the company has also had some difficulty, with the Blue Cross Blue Shield Association rejecting an appeal by Cyberonics last month to pay for the device.

Cyberonics, which faces delisting of its stock from the Nasdaq market as well as a U.S. securities probe over stock options, obviously has a lot riding on Medicare approval for treatment-resistant depression using the VNS therapy.

In a statement, Cyberonics said: “Today is the last day of a 30-day public comment period at the Centers for Medicare and Medicaid Services (CMS) regarding reimbursement for VNS Therapy for treatment-resistant depression. In the last 30 days, 1,236 qualified psychiatrists and physicians, patients, caregivers and families submitted comments encouraging CMS to reimburse for VNS Therapy for treatment-resistant Depression.”

The company declined to comment further.

Although the FDA has approved VNS for severe depression, Public Citizen noted that the Social Security Act allows Medicare-sponsored reimbursement only if the device is proved “reasonable and necessary,” which Public Citizen contends it is not. This is a more rigorous standard than that followed by the FDA, which requires that a medical device need only be proven safe and effective.

Public Citizen alleges that Cyberonics has yet to live up even to the FDA's own standards. It said that Cyberonics conducted a three-month study of VNS' effectiveness in which half the participants' VNS devices were not turned on. VNS patients fared no better than patients whose device was not turned on. Instead the company has relied upon a series of non-randomized, unblinded studies with questionable control groups to make its claim for the effectiveness of the device.

Cyberonics' request to CMS is an eleventh-hour attempt to save a failing product, Lurie said. Because of the unfavorable reimbursement decisions, the company estimates that only 1,600 devices had been implanted as of July 2006.

Aside from all its potential legal problems, Lurie also said that the company was recently embarrassed because it arranged for a ghostwriter to pen an article touting VNS in the journal Neuropsychopharmacology. The journal neglected to disclose that all eight academic authors, including the journal editor who was the lead author, had received financial support from Cyberonics. The editor resigned as a result.

The Senate Committee on Finance has conducted an investigation into VNS' approval for severe depression. The investigation, released in February 2006, revealed that at least 20 senior FDA staff had recommended against approving VNS for severe depression, with none favoring approval – but the director of the FDA's Center for Devices and Radiological Health (CDRH), Dr. Daniel Schultz, overruled them all.

Schultz's approval followed the backing of the FDA's Neurological Devices Panel, which voted its recommendation to approve the depression indication 5-2 back in 2004 (MDD, June 17, 2004). Still, the Senate committee, which for two years has been investigating the decision-making processes at the FDA, could find no previous instance in which the director of the CDRH had approved a device in the face of unanimous opposition from staff scientists and administrators beneath him, the report said.

The FDA's decision to approve the device has been the subject of an investigation by Sen. Charles Grassley (R-Iowa). Grassley, the U.S. Senate Finance Committee chairman has said he worried the device might not meet the usual FDA criteria for safety and effectiveness.

“FDA's approval of VNS for severe depression was an embarrassment, both scientifically and procedurally,” said Lurie. “Now is the time to set the record straight by revoking approval for this device.”

In a previous interview Cummins told MDD that the Senate committee report, released in February (MDD, Feb. 21, 2006), was just one in a long list of problems for the company stemming from the public's misunderstanding of what just exactly TRD is.

“One of the many challenges that Cyberonics has continuously faced during its eight-year research program to develop the first safe and effective treatment option for Americans with chronic or recurrent treatment-resistant depression is that very few Americans understand TRD and can distinguish it from depression,” Cummins said.

Cummins said he believes that ultimately the company will get a positive national coverage policy decision from CMS for use of the VNS therapy in TRD patients.

“What's going to carry that day and argument is not a Senate Finance Committee report, not statements by Sen. Grassley – not statements by inexperienced, underqualified FDA junior bureaucrats. What's going to carry the day is the data and the opinions of experts.”