Psychiatry and the surgical treatment of depression, Part II
The previous post expressed my "squeamishness" with this kind of surgical solution for modifying mood and behavior. In the end however, I recognized both the paralyzing impact of severe depression and the need to accept any therapy that is proven to work where other less invasive therapies have not.
I closed with an admonition that "when we're dealing with those aspects of our being that cut at the very heart of our humanity, we need to be especially careful."
Unfortunately, regarding this device, it appears that such has not been the case.
In June 2004, an FDA advisory committee recommended such approval. However, the following August the FDA denied approval pending further data from the company. (Advisory committee recommendations are not binding and can be overruled by the agency.) Recently, the FDA announced that it is reconsidering approval for the marketing of this device for the treatment of intractable depression.
In a randomized trial, the vagus nerve stimulator was implanted in 235 severely depressed patients. In only half of them, was it turned on. 17 of 111 such patients reported significant improvement. 11 of 110 in the control group did. (No mention was made of the remaining 24 patients.) The difference was not statistically significant which means that it could have been attributed to mere chance. In other words, efficacy was not demonstrated by this study.
In addition, this device is not without side-effects. Patients have complained of hoarseness and "odd" inflections in the voice. At least one patient cited a constricting pain in the back of her throat which at times left her unable to speak. In addition, removal is technically difficult should this ever be necessary and the wire leads must generally be left in place. It should also be noted that there are only two years of safety data thus far which is not much for a device that presumably will be left in for life.
So why did the advisory committee approve this device? With no phase III trials demonstrating efficacy and no long term safety data on depressed patients, their decision amazes me. This hardly seems the appropriate background for a "reasonable assurance" of safety and efficacy as mandated by the FDA. As it turns out, this recommendation appears to have arisen largely out of emotion.
The committee's chairperson, neurologist Kyra Becker MD made the extraordinary statement that if she had voted her conscience, soley on the basis of the evidence, she would have voted not to approve.
Then on what basis did she vote? I've heard some poorly thought out statements to the media before, but this one redefines the term malapropism. She also relates that "the whole meeting was uncomfortable, and everyone wanted to see another trial done, no question about it." So why vote for approval before such a trial was done?
Dissenting committee member Dr. Richard Malone said "I walked out of there thinking I was nuts. It was stunning..."
Since there are so few options remaining for patients with intractable depression, grasping at straws can seem the compassionate thing to do. Unfortunately, such decisions can have unintended consequences.
First, severe depression almost always has other treatments that are efficacious, usually in the form of multi-drug regimens. This being the case, treatments with unproven efficacy might very well direct a patient away from other potentially beneficial therapies. In fact, with FDA approval, there is nothing to stop physicians enamored by high tech solutions from utilizing this device in patients with even moderate depression (or severe depression for which established therapies haven't been exhausted.)
Second, any treatment such as this device that may be capable of making depression better, may in fact make it worse. What would we think if down the line, we found higher rates of social dysfunction or suicide among those who opted for this product? Every intervention has potential downsides.
Third, should a device with essentially no established benefit be allowed to be aggressively marketed by the company? This is exactly the right that FDA approval would grant. Should insurance companies and other third-party payers be required to foot the bill for this $15,000 treatment (not including the costs of implantation and maintenance)?
For these reasons, the FDA needs to make a well thought out, rational decision, not one based on emotion as has apparently been done by members of this committee (especially the chairperson).
I agree that there are many bureaucratic obstacles to FDA approval of medical technology, many of which are manifestly unnecessary. Demanding proof of safety and efficacy is not one of them.
As an aside, I will mention that there are some questions about the propriety of the FDA's reconsidering approval in this case:
"Cummins (Cyberonics Chief Executive Robert Cummins), who personally owns 1.15 million Cyberonics shares, acknowledged the company appealed to a number of Republican and Democratic Senators and Congressmen, as well as the Senate Finance Committee for help after the negative decision from the FDA."I'll leave it up to the reader to ponder the morality of doing an "end run" around the FDA.