Top FDA Official Approves Medical Device Despite Lack of Efficacy
NOTE: The following is one of a series of case studies produced by the Union of Concerned Scientists' Scientific Integrity Program between 2004 and 2010 to document the abuses highlighted in our 2004 report, Scientific Integrity in Policy Making.
In an extraordinary move, a top Food and Drug Administration (FDA) official approved a medical device against the unanimous opinion of his scientific staff in February 2006. Dr. Daniel G. Schultz, FDA's Director of the Center for Devices and Radiology and Health, approved a surgically implanted vagus nerve stimulator for treatment of cases of severe depression even though, as reported in the New York Times, the device "had not proved effective against depression in its only clinical trial for treatment of that illness."¹
FDA scientists "repeatedly and unanimously" recommended rejecting approval of the device, manufactured by Cyberonics, as a depression treatment, though at one point an advisory panel did provisionally recommend approving the device. An investigation by the Senate Finance Committee found that Dr. Schultz had overruled more than twenty FDA officials who recommended against approval.² According to the New York Times, the decision represented the first time in the agency's history that a director "approved a device in the face of unanimous opposition from staff scientists and administrators beneath him."³
The vagus nerve stimulator is surgically implanted into the base of the neck and sends electrical signals to the heart, brain and other parts of the body.4 The device was approved as a treatment for epilepsy in 1997. The company requested FDA approval for treating cases of severe depression after some device recipients reported improved moods. Anecdotal evidence suggesting that the nerve stimulator could help seriously depressed patients did not hold in clinical research. The one comprehensive study of the device in clinically depressed patients failed to show convincingly that the device had any positive effect on the patients.5 Critics have detailed how, following the initial failed trial, Cyberonics has "relied upon a series of non-randomized, unblinded studies with questionable control groups to make its claim for the effectiveness of the device."6 In short, Cyberonics never proved its device to be safe and effective, as is required by the FDA.
By overruling his scientific advisors, Dr. Schultz set in motion a potential windfall for Cyberonics. Public Citizen reported that the market for patients with epilepsy using the device was approximately 30,000, but the potential market for sufferers of treatment-resistant depression was over 4,000,000. The FDA defended the apparatus' approval as a means for helping those with severe depression who "are otherwise on their way to institutionalization, because of the seriousness of their illness."7
The New York Times, however, reported that FDA reviewers were "bewildered" by the decision. As one agency scientist said, "in my opinion, they do not have adequate data, and I don't understand how this can move forward." Another scientist argued that approval of the device was "akin to approving an experimental product."8
Dr. Peter Lurie, deputy director of Public Citizen's Health Research Group, argues that the FDA needs to relearn a simple principle: "If it doesn't work, it shouldn't be approved."9
1. Gardiner Harris, "Device Won Approval Though FDA Staff Objected," New York Times, 17 February 2006, accessed 22 September 2006.
2. Committee on Finance, United States Senate. Review of the FDA’s approval process for the vagus nerve stimulation therapy system for treatment-resistant depression. February 2006, accessed December 8, 2006.
5. Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biological Psychiatry 2005;58:347-354.
6. “Electronic Device Should Not Be Approved for Treatment of Depression, Public Citizen Tells FDA,” Public Citizen, 11 May 2005, accessed 22 September 2006.
9. Public Citizen.