The FDA and FMT regulation. Part 1.
The only update available since the last blog a year ago is the fact that we’ve received over a million applicants and still haven’t found one that meets the ideal criteria. The FDA saw that and thought "Ha, these guys have it too easy". They sent me a warning letter about the regulatory status of FMT. I responded and haven’t heard back yet.
To be honest, I'm glad "something" happened, as I've been getting extremely burned out screening so many people who don't qualify. It makes this feel like an incredibly useless endeavor.
Some background/history:
The Human Microbes (HM) project started out much like the famed Dallas Buyers Club, but with poop instead of a drug, and with much greater implications and potential for the whole of society.
I am just one patient who spent years trying to work through "official" channels to improve the quality and availability of stool donors:
Another email I've been sending to researchers regarding donor quality (Nov 2018)
FDA announces public hearing in Maryland on Nov 4, 2019. Here's what I'm writing up to submit.
It eventually became clear that this was a case of “if you want something done right you have to do it yourself”.
I think most people severely overestimate the competence of our research, medical, and regulatory systems. Out of all the hundreds of FMT clinical trials in recent years, I only recall one or two that went out of their way to try to find a highly effective donor. Donor quality was barely being mentioned and considered until I started posting about it and writing to hundreds of research groups. And then, even one research group that wrote about donor quality went on to largely ignore it in their subsequent studies.
I realized that no hospital or single doctor or clinical trial is going to spend years screening hundreds of thousands of applicants to try to find a "super-donor". No profit-driven company/entity is going to invest the time and money into something this experimental, which has numerous lost-investment-related problems even if you successfully find a super-donor.
Even philanthropic organizations seem averse to spending the time and money on something this experimental and unknown. And unfortunately, some of them, like the Gates Foundation, seem busy pulling the tug-of-war rope in the opposite direction.
There's a reason (capitalism) this project didn't happen until a disabled patient started it. And anyone other than a severely ill patient with no other options would have given up a long time ago, considering the circumstances (which I won’t get into here).
I’ve been dismayed and disturbed by the amount of people who would prefer to sit around and wallow in their misery rather than take any action to better their circumstances. But there are still those of us who are not willing to do nothing while our lives waste away in agony when a cure exists but no one is motivated enough to obtain it.
When starting up HM, I had the intention to run it as a clinical trial and register on clinicaltrials.gov. But all I could find were companies charging $1,500 to tell you whether or not it was possible. I also contacted the FDA about getting approved for an IND (investigational new drug) application and never heard back. So I continued as is.
The FDA is currently regulating FMT as an Investigational New Drug (IND), which seems poorly applicable to stool/FMT. Poop is not a drug and I am not developing a drug. I’m searching for people healthy enough to be stool donors. Researchers, doctors, clinical trials, etc., can then purchase stool from our donors. I’m not sure what the exact requirements are, but it is widely stated that IND requirements are extremely onerous. Some sources also give estimates of an IND costing millions of dollars [1][2][3], and one even quotes $1 billion.
When looking for a donor for myself I wanted a list of items to be able to judge donor quality. No one would provide them. That is now what HM provides to recipients:
Full anonymized health questionnaire
Proof of physical fitness
Pictures of stool type
Each donor’s results with other patients
I have done everything in my power to be as transparent, trustworthy, scientific, safe, and effective as possible. I have run HM exactly how I think FMT should be regulated and how I'd want an FMT provider I was interested in purchasing from to be run.
Excerpts from my 6-page letter to the FDA:
As outlined in many places on our site, we think that donor quality deficiencies are the main reason why FMT clinical trials have been getting poor results. So we are trying to solve that. So yes, we do want clinical trials, doctors, researchers, etc., to use our donors for "the treatment or prevention of various diseases". However, we are simply a source of stool donors -- people can (and do) purchase stool from our donors for any reason. But we do have to make it clear to anyone who may need to source stool for FMT, that our donors are being selected and ranked for their purposes.
For example, a doctor may want to treat a patient with FMT for C. difficile. My understanding is that is the situation where your "enforcement discretion" guidelines come into play. Where is that doctor supposed to find high-quality stool? I think we are the ONLY high-quality source.
Also relevant are my recent statements that I've screened over a million applicants at this point and still haven't found one that meets the ideal criteria. So the chances that that such donors will be found and made available by any means other than the Human Microbes project seems nigh impossible.
Each donor is so unique. I think I found a donor that would be very effective for obesity/weight loss. Yet they're just sitting around with no demand while expensive pharmaceutical drugs that do not solve the crux of the issue, and have bad side effects, are being heavily marketed. And FMT clinical trials for obesity are getting poor results due to the low-quality donors they're using.
I have thousands of donors better than what are currently being used worldwide, yet my donors are not in high demand because there is no incentive for institutions to use higher quality donors. My lowest "C. diff only" category are all far better than what hospitals, stool banks, and clinical trials are using.
I'm growing more skeptical of published results. I think they're not properly tracking & reporting bad outcomes. They are likely brushing many detrimental side effects off as "unrelated" when they're not. And the quality of donors they're using doesn't match their reported outcomes.
Since we pay so much more than anyone else, virtually every donor that’s been covered in the news has applied to HM. Donors from all major clinics, stool banks, companies, and clinical trials. The vast majority do not qualify or rank high. And some who have been declared “super-donors” have had conditions themselves that are likely to be cured or transferred via FMT. That this quality of donor is the "best of the best" currently being used should be very alarming, as well as extremely depressing for those of us whose only/main hope is FMT.
Do you really want us to switch to selling poop for recreational purposes, stop all tracking & reporting of results, and completely change the wording on our website to make it ambiguous about what we’re doing and thus impossible for people to find us? Who does that benefit? We should be regulated. But as what we are -- a source of stool donors. Not as a drug developer with regulations that are unachievable.
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I'm doubtful that this project would work at all in any other way than the current model.
Firstly, there is not enough demand currently to hit the "$180k/yr" figure. No one else would be doing this except me -- someone who's already disabled and thus only cares about the outcome and doesn't need to make a living (I have been living off social security disability).
Secondly, not only does the vast majority of the income currently come from random individual purchases, but so do the results. And those results are essential as a "proof of concept". I've been contacted by multiple research groups interested in doing FMT in a clinical trial. They already seem extremely locked into a rigid mentality where they're averse to doing anything unique. If we had zero results/active donors there would be even less basis for them to consider us.
Thirdly, there has to be active demand for donors to be willing to apply. People already see "get paid $500 for your poop" and think it's a scam. If we had no recipients no one would bother to apply. "One in a million shot to qualify, and if you make it you don't even get to start making money until some random clinical trial decides to use you, which may never happen."
Fourthly, we do zero marketing to recipients and include many warnings about the experimental nature of FMT. This is something that fully-informed people are seeking out on their own and choosing because they've tried everything else and aren't willing to wait decades more for the extremely flawed research system to keep failing and running useless trials with low-quality donors. My only goal is to find a curative stool donor. All of my time and energy is spent screening the million+ donor applicants. After I find one, I may even shut down willfully. It would be schadenfreude to see people have to struggle for it like I have been made to.
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A page discussing the limitations of testing, and how overreliance on testing is a sign of a low-quality source of FMT. And another page on how our screening process accounts for that.
Some examples of why regulators should be working with HM to elucidate the donor quality puzzle. We are testing and discovering things that no one else is/can. Things that everyone has been ignoring, with regard to donor quality.
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There are absolutely risks to FMT, but we do our best to make recipients fully informed of this, and we take these risks anyway because we have nothing else. I think that the fact that there are those of us willing and able to take these risks is a benefit for everyone.
People saying “don’t DIY” should be saying “don’t use some random donor”. People are not going to stop doing DIY FMT (swallowing capsules is not difficult). They're going to go back to using whatever "best" donor they can find, which often ends up with them getting worse and developing new problems. And all tracking and reporting of results will cease. Who benefits from this?
Chronic disease is rampant all over the world and is continually getting worse. The solution may be as simple and readily available as eating the poop of someone healthy -- something animals naturally do (coprophagia).
"Eating ass" has become a popular sexual behavior discussed on social media. This is essentially DIY FMT, and it's probably a terrible idea since the vast majority of people whose ass is being eaten are unhealthy and come nowhere near qualifying as a stool donor. And predictably, there are anecdotal reports on social media of people contracting new problems from their partner from this practice. The only way to reverse the new problems is by using a better donor. It shouldn’t be illegal/impossible to find someone healthy enough and pay them for their poop.
When Openbiome shut down my thoughts were "Great, now people will finally have to look for higher-quality sources of stool". If HM shuts down, that will pretty much be the death knell for FMT.
Without HM, people are stuck with extremely poor sources of FMT. One example is an extremely disreputable group that capitalized on this perfect storm of desperate people and lack of alternatives. The FDA is not blameless in this situation. If the FDA does not allow reputable sources to exist, people will resort to the only other options.
I experienced this myself -- my health was severely declining with no other options and I used a low-quality donor because there was nothing else. I got worse and developed new problems. With Human Microbes, I've worked through tremendous hardship to make it so that no one else has to make that same choice.
My suggestion to regulators:
I don’t think it’s possible, or a good idea, to regulate FMT like a drug, probiotic, or any other common item. I think FMT is unique and requires unique regulation. In one of my recent reports I included my suggestion to regulators:
I think FMT will be very hard to regulate. It's very complex. It depends a lot on the integrity, intelligence, knowledge, and motivations of the people running the company. I'm not sure that you can make FMT "guaranteed safe". The best you could do is allow patients to make informed decisions. I think much of the "good safety record of FMT" is likely due to poor/lack of tracking of longer-term outcomes. Antibiotic studies have the same issue. Antibiotics are definitely not as safe as they're widely considered to be. Companies and clinical trials are both getting away with "well we did the bare minimum pathogen testing so our donor was safe".
Even if I shared the answer key with every stool provider there's no guarantee or even strong incentive for them to use it. So my advice to regulators would be to mandate the public tracking & reporting of results like we do on our website. With the ability for patients to provide long-term updates at will. And dole out company-killing fines for not doing so. This will provide some incentive for providers to care about, and try to avoid, poor patient outcomes. As is, it's largely a black box besides some random reports on social media. A large percentage of people can and do get worse and it has nearly zero impact on the company because few future-customers/patients find out about it.
It is safe to assume that any provider that is not publicly tracking & reporting results has a large percentage of patients getting worse and developing new problems.
You could mandate that stool sources must post an obvious link on their webpage to their results. The FDA could even set up its own website for tracking & browsing results from all sources. Doctors and patients would be able to browse these results before deciding on FMT and choosing a source, and doctors could collect the results from their patients and submit them to the FDA website. This should make the results more reliable and standardized across all sources.
You could mandate that if the stool is being used to treat any condition it has to be shipped to a doctor's office. I would actually prefer this, but due to the regulatory status of FMT, most doctors are unwilling to get involved.
You could mandate that recipients be fully informed on the experimental nature of FMT and the need to review donor quality and results before trying it. I would recommend the FDA create a brochure that has this info, and mandate the distribution of that to any patient seeking FMT.
See our next blog for more on the future and potential of FMT.
What do you think FMT regulation should look like?