Sunday, August 29, 2010

Spinal Fusion Devices: What's the FDA Hiding?

Thanks to Marilyn Mann, I was directed to this article by John Fauber on MedPage Today Orthopedics:

(Regular readers will recall that we've seen Fauber's excellent investigative reporting previously with the Milwaukee Journal-Sentinel.)

The story is a complicated one and I refer interested readers to the full report. A couple of medical device companies have manufactured some stuff that makes the body grow new bone wherever it lands. The idea is to put it in a little cage sort of thing to contain it, slip the cage in between two vertebrae of a person who otherwise would undergo a spinal fusion to lock the two bones together (using a bone graft, with a bit of bone taken from the hip), and you have a fusion done without the need to harvest the bone from another site.

Two problems. First, the above story assumes there's some advantage to spinal fusion surgery in the first place. In the vast majority of cases this is highly questionable. However, since surgeons make a lot of money off fusions, and since patients with chronic back pain are among the most desperate and unhappy patients known to medicine, it seems spinal fusion will be among us for some time to come, evidence be damned.

Second problem--the magic stuff that makes new bone wherever it lands really indeed has a Midas touch. Numerous complications have been reported where new bone grows where you don't want it. This is especially bad in the neck where there can be swelling that compromises breathing.

This whole business made some folks wonder about the original FDA hearing at which this magic stuff was first approved. It turns out that most of the favorable data was generated by docs who had financial conflicts of interest with the manufacturer. The stuff was approved with a label that said don't use it on the neck, use it in the lower back only, but even at the time people warned that off-label use would be highly predictable and a huge problem. Guess what? Since 2002 off-label use has been a huge problem.

So these folks went to the FDA and asked for a simple piece of information--tell us the list of investigators, whose data were reviewed by your advisory board in 2002, that indicate which of them had financial conflicts of interest with the manufacturer.

Seems simple. But the FDA has said that this data cannot be released. More interesting, the FDA has provided, on three occasions, three totally different reasons why the information cannot be released. The company, of course, has it, but refuses to release it.

Now, a couple of observations. First: we come back regularly to the issue of how devices are different from drugs. This seems to be a case in point. Whether the stuff will leak out and cause bone to grow where you don't want bone might very well have something to do with the technical skill of the guy doing the surgery. One of the most conflicted surgeons in terms of total money brought home, is conflicted because he's credited with inventing the device. It would not be surprising to learn that the surgeon who invented a particular operation has better outcomes than your average surgeon off the street, even if for no other reason than he's had more time to do more surgeries. So you can't draw quite the same conclusions as you might if this were a drug being studied and not a device.

Second: This is related to the first. Given all that, you can see how a company might behave if research integrity and public trust were actually Job One in their value system. They would realize that having the bulk of their research carried out by folks with serious conflicts of interest was not a good thing. So as early in the game as possible, they'd ask some hard questions about the research strategy. They'd specifically look for ways to launch a clinical trial under conditions that as much as possible eliminated financial conflict of interest as a variable. They'd insist on several layers of disinterested third-party monitoring as a minimum condition. And so on.

So far as I can tell, none of those steps were taken; the company simply figured it could go about its usual business, using its own hired guns, and then push around the FDA approval process to get what it wanted (in this case, an approval that opened the doors wide to off label use and hence increased sales, and that asked no embarrassing questions about who needs spinal fusions anyway). The company was correct in its assessment of what it took to get what it wanted.


Anonymous said...

I'd like to know where the hospital IRB's are. If these surgeons are using the devices off label, that would be considered an investigational use, right? As such it should fall under the auspices of the IRB to review and approve these surgeries.

It seems not only the FDA is negligent here but also the oversight committees at the local level as well. Doctors of course have their own profit driven motivation for recommending said surgeries. Who oversees the doctors?

Howard Brody said...

In reply to Anonymous, it's important to keep in mind that once a drug or device is approved by the FDA, physicians legally can prescribe it for any use their judgment dictates, including off-label uses. The decision to use a drug or device off-label in any given patient is therefore NOT an investigational use, and no IRB approval need be sought. So IRB's are completely out of the loop when it comes to regulating off-label prescribing. The proposals now circulating call for stricter informed consent requirements if a physician is going to use a drug/device off label, so that at least the patient should be aware--but again, this is informed consent in the therapeutic and not in the research context. Thanks for writing, Howard

Anonymous said...

Thank you for your reply Howard. With all due respect, IRB's have the authority and latitude to require approval prior to using any product for off-label use.

The FDA in their guidance on off-label use states:

"Use of a marketed product in this manner when the intent is the "practice of medicine" does not require the submission of an Investigational New Drug Application (IND), Investigational Device Exemption (IDE) or review by an Institutional Review Board (IRB). However, the institution at which the product will be used may, under its own authority, require IRB review or other institutional oversight."

I believe that while FDA needs to step up on these issues (as a former FDA investigator) I also believe that hospitals and other professional licensing and accrediting bodies also need to step up to their responsibilities.

Howard Brody said...

Anonymous-- thanks for the clarification and I apologize for any misimpression. I agree that institutions could, if they wished, do much more to crack down on off label use, which I think is the most important point; and I appreciate your clarification that this could fall under the role of the IRB. Thanks again, Howard