Sunday, June 2, 2013

The FDA and Fecal Transplants

The FDA has recently put the medical community on notice that the use of fecal transplants for the treatment of Clostridium difficile diarrhea constitutes use of an unapproved biologic.  This is another fascinating and discouraging FDA intrusion into medical practice that threatens to set back the use of a clearly beneficial and safe therapy for years. What is wrong with these people?

First, there are a number of studies published on the use of fecal transplants in the treatment of this deadly infection.  C. difficile diarrhea is estimated to kill 14,000 Americans every year and the numbers of fatalities has steadily risen over the last 20 years or so. Although initial therapy is 90% or more efficacious, the relapse rate is as high as 25%.  For those patients who have multiple bouts or whose initial infection is especially severe, fecal transplants offer superior efficacy in every study performed so far. The best review of this topic can be found via this link. In one controlled study (albeit small), the efficacy of fecal transplant in recurrent C diff diarrhea was 81% and that for standard therapy was 31% - a very statistically significant difference. In the studies reported so far – hundreds of patients treated – there have been no important safety signals whatsoever. Therefore, the risk benefit ratio appears to be all benefit and no risk.

In addition, the procedure is not so pleasant.  One obtains stool from a volunteer or volunteers, suspends it in saline and milk, filters it through gauze and administers it to the patient via a nasogastric tube inserted through the nose going to the duodenum.  The patient has to have a bowel cleansing with massive laxative therapy the day before the transplant and has to take a pill to reduce stomach acid prior to receiving the stool transplant.  Sounds like fun for both physician and patient, right? This means that not everyone is going to want to do this and only those with a significant problem will do so.

So – what is the FDA’s problem? First, they are not in control. Beyond that, I suppose they interpret this intervention as doing their job to protect Americans from unsafe and ineffective therapies.  But other than the studies done so far, what do they want?  If they want larger, controlled studies, who will pay for these studies?  How long will they take? Will we have to have a manufacturer that is approved provide a volunteer stool sample within 6 hours so it can be used?  How does that work?

Also – which FDA are we speaking to?  The letter comes from CBER.  But I understood that the use of biologics for therapy would be regulated through the antiinfectives division in CDER . . . ??

This entire approach is reminiscent of the FDA’s disastrous attempt to make antibiotic trials more stringent by making them impossible to perform or impossibly expensive to perform or both.

My recommendation here is that the FDA get together with Gastroenterologists and ID specialists and define a clinical guideline similar to the Cleveland Clinic approach such that physicians are aware of a recommended standard approach to this procedure.  But the FDA should not be regulating this.  This is yet another bridge too far. 

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