It seems that once again I am donning my ‘scientist’ cap and wading knee-deep into the shit…
Literally:
A hospital physician from a major B.C. facility says several patients died in the last year from C. difficile — unnecessarily — after the health authority stopped her and her colleagues from giving an experimental, simple and highly effective treatment… The treatment, called a fecal transplant, involves introducing stool from a healthy donor — usually a relative — into an infected patient’s bowel, usually through an enema.
Yes, you read that correctly. Dr. Jeanne Keegan-Henry is proposing transplanting somebody’s poo into the bowels of someone with a Clostridium difficile infection in order to cure them.
Poo.
Transplant.
Poo Transplant.
It sounds like the name of a doomed-to-obscurity high school punk rock band. And yet, Dr. Keegan-Henry, who is by all accounts an able and qualified physician, is recommending it. Skeptical smackdown time, right?
Here’s the crazy thing about skepticism. Detractors would characterize it as being resolutely opposed to anything that doesn’t sound like Big Pharma drugs, or is too experimental or outside the realm of conventional medicine. While it is often worthwhile to listen to the criticisms that come from one’s enemies, it is important to resist the temptation to allow them to define your position. More often than not, they are all too happy to succumb to the temptation of straw-manning you into oblivion rather than give a dispassionate description of what it is you actually think (cue the peanut gallery coming out of the woodwork to point out the many times I’ve done it to them).
Skepticism is about evaluating claims, all claims, according to their plausibility and the evidence supporting their truth. When I first caught wind of poo transplants (reader’s note: this article will be stuffed full of poop jokes – you have been warned) my skeptic hackles immediately went up. It’s really the prototypical case – we have a brave maverick doctor who is standing up to the medical establishment and recommending a completely natural remedy to a condition that is usually treated with drugs. For bonus points, it involves enemas. Seems like this ripe stinker was dumped right on our plate as another crazy whackaloon looking for attention (and possibly a book deal).
So, what does a skeptic do? She goes to the evidence! A quick search on PubMed (the U.S. National Library of Medicine National Institutes of Health centralized research database) for “fecal transplant clostridium difficile” reveals 30 hits – not exactly a stellar start; usually it’s in the neighbourhood of a few hundred to a few thousand results. The majority of these hits were commentaries and letters rather than full-blown research articles – also not a good start; what we’re looking for is systematic reviews of clinical trials, or at least trials themselves. We don’t have that – what we have is a handful of case series reports, each representing a tiny number of patients.
So I took a look at the largest case series, that of a 12-patient sample. And the results? Well… would you forgive me if I say “holy shit”?
Click to enlarge
Of 12 patients with infections ranging from 79 to 1532 days (mean length = 352 days), 100% of the patients in this sample experienced a clinical response, defined as “cessation of diarrhea, cramps, and fever within 3 to 5 days”. The authors describe their inclusion and exclusion criteria clearly, as well as the treatment protocol. Patient followup ranged from 3 weeks to many years after the intervention (which is a necessary evil of a case series – it’s not a prospective trial where follow-up can be standardized).
So, cut and dry answer right? Obviously it worked for these patients! No need for further study – let’s approve the shit!
Not so fast…
The reason for putting on the brakes (and possibly leaving skid marks) is that this is one sample of patients. These results are certainly dramatic, but there were no enterobacteriology cultures done – the gut was not examined to see if it was truly the poop that did the trick. The patients from whom the samples were taken had taken doses of antibiotics before donating their sample – was it the poo or the drugs that done it? Even the authors of the paper admit that they don’t have a certain mechanism by which fecal transplantation works. There are certainly some plausible attempts at explanation, but they still don’t know.There was also no control group for comparison (although in a time-series design it is permissible to use the patients as their own controls, comparing them to their pre-trial state – I am channeling that degree in epidemiology!), meaning that we cannot rule out the placebo effect or some other event as explanatory.
Is Dr. Keegan-Henry right? Should we be allowing fecal transplanation? Maybe – the preliminary results are certainly compelling (to go from years of suffering to resolved in 3-5 days is really remarkable). We should be enrolling people in small-scale clinical trials to test for efficacy. Given that there are no observed adverse effects of the transplantation, there’s certainly no reason to block the investigation:
Dr. George Sing, a gastroenterologist at Burnaby Hospital, also wants to provide the treatment to patients. “We did table [a proposal], but it fell into the cracks,” said Sing. “We have been through all the channels … but when it goes through committees it gets bogged down.”
Heh… he said “fell into the cracks”.
This is the hallmark of skepticism – even if something looks totally batshit insane, we test claims against evidence, not against what we think should work. I’ll be interested to see if this story develops.
that is the NASTIEST shit I ever heard!
I think I’ve heard of this before. The idea is that the transplant is supposed to replace the digestive bacteria in the bowels to help the patient. No clue if it works though, and I’m not getting in line any time soon.
Based on the case series (these were done retrospectively on 100% of patients who had received the procedure), it does appear to work quite well. Time-series designs are notoriously tricky, and obviously there is no control group so we don’t have the type of strong evidence we’d like to have when making this decision.
That being said, it’s a non-invasive procedure (nasogastric tubes aren’t pleasant, but there’s no cutting) that is essentially low-risk. Although, as Kid notes, it’s pretty nasty.
We had a PI, (Bruce Vallence) talk to us about this in Experimental Medicine 501. He proposed that a poo transplant may be useful in patients with colitis or Crohn’s disease. The microbiota in inflamatory bowel disease (IBD) patients has been altered by the disease, (to a higher gamma proteobacteria content and less bacterioides families) either as a cause or as an effect. The normal microbiota in the donor’s crap will repopulate the recipient’s bowel, and perhaps alleviate some of the symptoms.
He showed good experimental results (mouse model) and there are some small clinical trials that have begun to see results. Also, several scientists in the IBD field are working on identifying the species of bacteria that populate the gut, but are finding that many are nearly impossible to culture (bacteria spores/colonies would be an easier sell as a treatment… so that you don’t have to eat shit).
Bizarre but potentially useful treatment.