Another kibosh

Increasingly, my work life seems to revolve around C. diff. Yesterday I performed three fecal transplants. All were elderly patients who had been suffering with recurrent C. difficile for many months. Using stool from OpenBiome's stool bank greatly simplified my job and made the entire process much easier for the patients. Since OpenBiome's donors are extensively screened, the patients did not have to identify a donor and bear the unreimbursed costs of donor screening. Family members of all three patients commented on the ease of the process, and were quite happy with not having to identify a donor. The daughter of one patient who been transplanted previously with a directed donor, specifically commented on her preference for using a standard donor. And as always, the patients and family members were incredibly grateful and very happy to think about life without vancomycin. I left clinic feeling as though I had made a real difference by providing these patients a therapy that still is unfortunately relatively rare. One of the patients yesterday had to travel three hours to see me for this very simple, yet highly effective treatment.

Last night, on the way home, one of our infectious diseases fellows called me to discuss fecal transplant for a critically ill patient in the ICU who was failing all the drugs we have available to treat C. difficle. I happily told him that fecal transplant should not be a problem as we have frozen stool now available in the pharmacy.

This morning I spoke by phone with a woman whose mother is hospitalized two hours away after having multiple recurrences of C. difficile regarding coming to Richmond for transplant. And a patient that I transplanted a few weeks ago (the first patient I transplanted with donor stool from OpenBiome) called to tell me how well he was doing.

It seemed as though the whole fecal transplant process was finally working very smoothly. But as I went to bed last night, I took a final look at my phone and saw an email from a colleague with a link to new information from the FDA on fecal transplant. Those of you who follow this blog may recall that the FDA had previously proposed that all fecal transplants would require an IND number; however, this requirement was later relaxed. I was stunned by the FDA's proposed new rule. Since the FDA seems to write in a different language, I will paste their verbiage here:

After publication of the July 2013 Guidance, FDA has continued to review this area and is clarifying its enforcement policy.  FDA intends to exercise this discretion on an interim basis, provided that:

1. The licensed health care provider treating the patient obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products.  The informed consent should include, at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks.
2. The FMT product is obtained from a donor known to either the patient or the treating licensed health care provider. 
3. The stool donor and stool are qualified by screening and testing performed under the direction of the licensed health care provider for the purpose of providing the FMT product to treat his or her patient.  

FDA does not intend to exercise enforcement discretion for the use of an FMT product when the FMT product is manufactured from the stool of a donor who is not known by either the patient or the licensed health care provider treating the patient, or when the donor and donor stool are not qualified under the direction of the treating licensed health care provider. 

So it seems that the FDA is not happy with the concept of banked stool from standard donors and would prefer directed donors. If I test a donor once for infections and that donor is known to the patient, I don't need an IND. But, if I obtain the stool from a stool bank that has a small number of highly selected donors that are tested serially every 60 days, and the stool is quarantined to avoid the problem of an infected donor in a seronegative window period, I need an IND? The blood bankers actually discourage the use of directed donors as the directed donor may be less likely to disclose risk factors for infectious diseases. There is no reason to think that would be different here.

I called the number on the FDA's announcement. The person I talked to was polite but I felt as if I was talking to someone in a parallel universe. After 10 minutes, I didn't feel like I had any better understanding of the issue. She told me that there were no data that fecal transplant is effective for C. difficile. Really? I reminded her that the randomized controlled trial published in the New England Journal was stopped early because it worked so well. She could not tell me whether I could even get an IND if I was using product from a stool bank, though later implied it could only be used in a clinical trial. She transferred me to "Manufacturing" and felt sure they could help me. The person in Manufacturing was not even aware of the announcement and said that I need to talk to someone in "Vaccines." Between this issue and the IV zanamivir issue, I have come to the conclusion that the FDA is so isolated and so sucked into the parallel universe of its bureaucracy that's it's lost touch with its mission.

While I might not be able to understand what the FDA is saying, here is what I do know: recurrent C. difficile is a terrible illness that is becoming increasingly common. In a subset of patients, antibiotics are not curative. It destroys quality of life, and if untreated in the elderly leads to wasting and ultimately death. A simple treatment is highly effective in curing the infection. And a group of really bright students in Boston found a creative solution to make stool transplants readily available and quite safe for patients. But a behemoth bureaucracy chooses to stand in the way.