The FDA and FMT regulation. Part 2.
Part 1, is required reading to understand Part 2.
I see a lot of patients blindly trusting the research and medical system, being eager for FMT clinical trials, and thinking that clinical trials are the best and safest source of FMT. To anyone with this mindset, I strongly encourage you to read through the links at the top of Part 1 of this blog series to learn just how bad the situation is and has been, and why I, as a patient, have been avoiding clinical trials and recommending other patients do so, long before I had any intention of starting up Human Microbes.
Similarly, I just learned that a research group that plans to use "patients who have undergone total proctocolectomy" as stool donors got an IND from the FDA and IRB approval. It seems clear to me that the current "IND + IRB" formula is grossly deficient. It allows extremely flawed and unethical studies to take place while preventing them from using high-quality donors from a 3rd party source.
In addition to one of the examples given in those links of a clinical trial doling out broad-spectrum antibiotics to healthy people, here’s another example of the kind of flawed and unethical research that gets used by big pharma companies to market a product that by its nature is harmful. They market it for a made-up condition and the FDA is apparently fine with that. Myself and other patients have been severely harmed by it, and we now need FMT to reverse the damage, and the FDA has been severely hindering us from being able to obtain it.
Surely if the FDA is this lax on other sources of FMT, and on inherently harmful drugs, they'd have no problem with a project like Human Microbes that is specifically & uniquely focused on safety and efficacy?
What is happening with FMT right now is quite similar to the situation during the AIDS epidemic, where the FDA was sticking to their “standard regulatory procedures” despite them being inappropriate for the situation. It was only remedied after the affected patient communities protested en masse [1][2][3]. Unfortunately, when it comes to FMT I’ve been virtually the only patient doing anything. “Dallas Buyers Club” is a movie about an AIDS patient who did the same thing I’ve been doing. Dr. Anthony Fauci was a central figure during that period and recently commented on that history:
When you describe that experience as enlightening, how did it inform your approach moving forward to confront other epidemics?
Dr. Anthony Fauci:
Listen to the patients. And don't think that everything comes from the top down. Listen to the community. Listen to what they're experiencing. And you're going to make a much better and more appropriate response to whatever the disease challenge is. That was a lesson that was very well-learned from the activists.
If I were in their shoes I'd be doing exactly what they were doing.
There are existing policies like the FDA Expanded Access program, FDA Enforcement Discretion and EUAs (Emergency Use Authorization), and state “Right to Try” laws, but none of them appear applicable to FMT or this situation. Mostly because the "drug" is not available without this massive effort from a patient to obtain it, and the FDA is hindering that effort.
Meanwhile, Nature (a highly respected science journal) released an article titled “Faecal transplants can treat some cancers — but probably won’t ever be widely used”. The reasons include “difficulties recruiting donors, demanding screening requirements”. Apparently, they’re oblivious to the fact that a single patient has solved these issues. It appears that no one cares that it’s been solved, and everyone would prefer to keep pretending it's an insurmountable problem. I have high-quality donors all over the world and no one is using them.
It's also disturbing to see how they're proudly advertising that they're using former colorectal cancer patients as stool donors for other humans. And the FDA has no problem with that.
In all my criticisms of the FDA, and in most of the other legitimate ones I've seen, the issue has been that they've been far too lax. However, there are some in that link that have to do with corruption and the source of the FDA’s funding.
I recently watched this video that presents a positive take on regulatory agencies. It gave me hope that the FDA would be on our side, and against the people who want to keep people sick in order to profit off of them with drugs that only treat some of the symptoms.
However, I also previously saw some more cynical takes that made me weary. For example, Dr. Alexander Khoruts (University of Minnesota GI, Director, UMN Microbiota Therapeutics Program) made a concerning and depressing statement about the FDA. He asks an FDA adviser "Does the FDA care more about profits or people?", and the response he gets is "One of the missions of the FDA is to protect the interests of commercial developers". Another question to the advisor: "How much influence does the industry have over the FDA decisions?", A: "A lot".
So will Human Microbes qualify as "industry"? Or are the "commercial developers" they want to protect the large pharma companies spending massive amounts of money on "synthetic FMT" drugs, which are currently little more than a multi-strain probiotic, cost $20,000 per dose, and owned by by one of the most hated companies in the world? Perhaps the FDA has simply been waiting for something like the Human Microbes project to pop up and figure out how to identify safe and effective donors to enable them to be widely available. Surely there are people at the FDA who want access to high-quality donors for themselves or their loved ones. Let’s find out.
After I published the previous two blogs and shared them with the FDA, they scheduled a video meeting with me. The following is what I sent them prior to the meeting (in addition to the info in Part 1).
My correspondence to the FDA:
Confidential information and examples of big risks patients are taking due to the FDA not allowing any other option to exist.
Examples of how we ensure informed consent, and steps we take for donor safety.
***
I thought about how the FDA is a consumer protection agency, so I will share some evidence below showing how unintelligently and unscientifically most people are going about FMT, and how you'd be causing more harm to them by removing the safest source of FMT they have. You are not protecting consumers by keeping a likely cure from them. Nor by leaving them with only low-quality sources of FMT.
When undertaking an experimental, unregulated treatment like FMT, it is common sense for patients to publicly track and report results so we can help each other make informed decisions about which sources are the safest and most effective. Yet virtually all the public results are either mine or screenshots/quotes I took of other people's experiences. Most people are basically just rolling the dice with a potentially deadly, unregulated medical product. And they continue to do so, and suffer the consequences of that, despite there being numerous public warnings about the nature of FMT and the sources they're choosing.
The current version of this blog post was toned down by someone who complained that it was too harsh, but here's a quote from the original, showing that I've had to threaten to ban people for not turning in their results, and even then, around 50% of people choose the ban.
A few months after orders were shipped out, and a month after recipients were requested to send in their results, only one person (of more than a dozen) had sent in their results. So I informed recipients that they wouldn't be able to order from any of our donors ever again if they didn't send in their results. Only around 40% of recipients have sent in their results. So possibly the rest are dead. At least we know that the fatality rate isn't over 60%. Of the ones who didn’t die, it seems like most experience mild to moderate benefits, while some people experienced no benefits.
It's dystopian enough that patients are having to research and develop their own treatments, and being unable to find someone who meets the ideal criteria after screening over a million people. There's no need for a consumer protection agency to try to stop them or make things harder or less safe.
Preventing people from accessing FMT because you can't guarantee that FMT is safe, is not the correct course of action. The potential downsides are worth the risk for those of us with no other options. You should focus on striking an ideal balance between safety and availability, and guaranteeing informed consent. I wrote to the FDA previously that I don't think proper informed consent is occurring at FMT clinical trials or any other source of FMT, and there are some examples of this below.
Millions of people are suffering and dying all the time from conditions that are likely treatable with FMT. It is very clear to me that the FDA is not striking the correct balance of safety vs availability.
Testing:
As a patient, when I found my own donors prior to HM (Human Microbes), I didn't put them through any blood or stool tests. Firstly, I couldn't afford it. Secondly, I see patients, clinical trials, clinics, stool banks, etc., all over-relying on testing, which creates a false sense of security/safety. Current testing can in no way determine the safety and efficacy of FMT.
Of course testing should be recommended, and done, but the frequency is debatable and the cost is a downside that seems rarely considered. We provide recipients the choice, and most of them choose not to bother with continually paying for more testing. If you mandate frequent testing that significantly raises the price for recipients, it can be more harmful than beneficial.
***
By far, the most transferrable donor characteristic, and the characteristic most associated with symptoms and outcomes, seems to be stool type. Not personality, not physical or mental traits. Yet HM is virtually the only source of FMT that takes stool type into account, much less focuses on it.
<confidential information about judging stool quality>
As you can see, stool is not a drug, and acting like it is, and keeping FMT from us patients is misguided and cruel.
***
Below are some examples of people developing/contracting severe new conditions from other sources of FMT. This doesn't happen with our donors.
This guy <snip> got worse and developed new problems such as severe weight gain, from a very fit donor who was accepted into a clinical trial and donated to a hospital for years, yet failed to pass our screening. The institution put in much greater effort than most places to find good donors and said this donor had a 100% cure rate for C. diff.
The chances that this only happened to this one guy who happened to be active in the patient community at the time, out of hundreds of patients who used that donor, are extremely small. More likely, similar things happened to dozens of other patients who used that donor but the results were not tracked properly and/or it was never reported anywhere. This is where your focus should be; rather than imposing severe restrictions on the patient who's trying to solve the problem. I'm doubtful that you're even informed that this is occurring. But regardless, you should be making sure that these kinds of results are tracked and publicly reported. In my previous letter, I shared links to letters I wrote to the FDA about this years ago. Yet nothing changed.
[Another example of someone getting much worse and developing new problems after getting FMT from “a world-renowned, official source of FMT”.]
Zero surprise when their donor screening exists of <snip> (standard things across most sources of FMT worldwide).
[Numerous other examples of people getting worse and developing new problems from “official” sources of FMT. Along with evidence that informed consent is not occurring]. Including new allergies, food intolerances, severe anxiety, GI symptoms, personality, severe weight gain, and many more.
Results are not being tracked. Patients are getting FMT from their doctors and then told "Off you go, you're all better now", then they develop new severe problems from the low-quality donors that were used, and no one finds out and it continues to happen.
There are a dozen more, as bad or worse, that I could pull up from these crooks, which would be one of the main options if people could no longer find and access Human Microbes.
This is why I thought the example you gave where one of our recipients temporarily experienced "increased intestinal pain, nausea, sweating, and loss of appetite among other things" as proof that our donors were insufficiently screened was absurd.
And even if things like this were happening from our donors it would be public information, obviously displayed on our website where people go to order, and thus proper informed consent. Perhaps someone would want their stool for non-FMT purposes, or someone may see something that makes them think the risk-reward ratio is worth it. Should the FDA be telling people they can't make that choice? Warning labeling is already a common way to allow many toxic & dangerous substances to be sold. Proper warnings, along with other measures I've mentioned previously, would be appropriate ways to regulate FMT.
***
You have approved other products that are far more risky and harmful than any of our donors. Many of us are in fact needing FMT to reverse the damage from these other products that you approved. These products do not come with relevant warnings that resulted in informed consent when we took them.
I believe we are the only source of FMT providing proper informed consent and tracking of results. Recipients are able to edit their results at any point in time, and we provide extensive documentation (FAQ, FMT page, wiki) on how virtually anything can be transferred with FMT, and any post-FMT symptom may be attributed to the FMT.
Since we track results publicly, our donors have an incentive to provide safe and effective stools to recipients so that recipients will see the results and want to keep ordering from them. For example, one candidate made it all the way through to the part where they were going to start sending out stools to recipients. They dropped out at that point. Probably because of the donor agreement, and because only at that point did they fully understand the consequences of sending bad stools to recipients, and because they realized recipients would not keep ordering from them if they sent bad stools.
***
In case it's relevant:
I plan to increase donor payouts to $1 million. It was already possible for donors to set their own prices, but now I'm explicitly advertising $1 million plus a $500k referral reward.
Blog rough draft: <snip>
A relevant quote from Dr. Anthony Fauci.
***
I realize it may not be in my best interest to share this information, but I feel like it's necessary for you to be well-informed on FMT.
I used to make as much information public as possible, but I reduced that due to a lack of reciprocation, and bad actors mimicking and leaching off of me. And this one has confidential information. My personal reports on the forum have most of my findings, and I've commented on some in the humanmicrobes.org blog.
Things I omitted from <one of my reports>:
<confidential information, including an example of how I've been sacrificing my own health to figure out FMT safety & efficacy>
I also knew from past experience that you can largely clear the detriments of a bad FMT with another good FMT.
After that, I started counseling donors to <snip>. Do you think other sources of FMT are paying attention to, and testing, things like that? Do you think they're discarding <snip> stools? I think it's extremely unlikely. I do not think that any other source of FMT is <snip> like I do. I think that if they were providing proper informed consent to their patients, tracking results publicly, and asking open-ended questions like we do (anything thing can get better or worse; what got better/worse?), most of their results would be as bad as the examples I previously shared.
<more confidential information>
Also, I noticed that people are writing articles about us and quoting the part of the warning letter where you say there is a safety risk due to inadequate screening. Firstly, the FDA doesn't even have a recommended screening regimen, so we use the international consensus guidelines, which are clearly displayed on our website. Secondly, you listed temporary side effects that are quite commonly reported in FMT studies that use the standard blood & stool screening tests. I elaborated a bit here: https://www.humanmicrobes.org/fmt-clinician-guidance. Thirdly, the statements in the letter seem to conflate donor screening with patients receiving medical oversight from their doctor, which are two separate things.
<more confidential information about the nature of FMT, and how operating a laboratory/stool bank does not negate major risk factors>
The point is that FMT is risky no matter what you do. I think one of the best safety features is the fact that our donors know that the safety and efficacy of their stool is what will get them customers. I specifically tell them:
It's important for you to do things correctly because both safety and efficacy can be impacted. And it's in your best interest to give recipients the most safe and effective product so they'll continue to order from you. We track and report results publicly, so you'll get to see how recipients are benefiting from your stool donations. That also means that if you send someone a bad stool you risk scaring off other recipients.
And for the other things I've seen people worry about, like antibiotic resistance, and COVID, the answer is donor quality.
***
I just watched news coverage of the presidential debate.
In my "blog preview" I facetiously wrote "The FDA was unwilling to use their authority to force people to help me find a highly effective donor". But you're not powerless. Even as individuals.
If any of you think it's a bad idea for the president to remain severely senile you may want to contact him and let him know about an experimental procedure that may significantly improve his function. I think he may take it seriously if it came from one or more of you.
He seems like an ideal candidate (for FMT) to me -- nothing to lose at this point and everything to gain.
I would recommend <snip> donor. There are other good candidates too. I just interviewed & added <snip> this morning. Trying a few different donors would probably even be the best idea.
***
I just re-read this:
After a new Nature article covered that topic.
I hope you guys read all the links at the top of this blog. It reminded me how bad the situation is and has been, and how egregious it would be for the FDA to be so lax on nearly everyone but restrict the Human Microbes project when we're likely the only one providing proper informed consent to patients, properly tracking and reporting results, and has donor quality standards that match the evidence and are far better than any other source.
Nature is writing articles about how "difficulties recruiting donors, demanding screening requirements and unease among physicians — have limited clinical uptake of FMT". Apparently, most people aren't aware that the Human Microbes project exists and has solved most of those problems.
The FDA’s response:
After all that, their response was simple and terse: Stop violating the law. Get legal advice from someone qualified because we won't answer your questions.
There was no indication that they had read anything I sent them. They even asked me before the meeting if I had any questions for them and I sent them a list of questions, and there was no indication they had read them.
In another universe, one of them may have contacted Joe Biden to educate him on FMT, and after Joe's health & cognitive function greatly improves from one of our donors he looks into our blog more and urges the FDA to make our donors more widely available.
Someone clarified that we would not only need an IND (Investigational New Drug application), but we would need an IND for every different condition being treated. So for "chronic disease" we would need dozens of INDs that each cost millions of dollars (maybe not).
After the meeting, they gave me contact info for another department and I finally got a response to most of my questions. Here you can read my questions, their answers, and my thoughts. You can watch that forum thread for further updates.
The summary is that they are all sensible regulations for drug manufacturing; but not for this unique situation. We would probably need millions of dollars in funding to proceed under the current guidelines, and the outcome would be drastically increased prices for recipients without being any safer. Simply supplying stool donors for clinical trials and for doctors to use is not within the current framework at all. If you are providing “the substance” then you are a drug manufacturer. Short of receiving funding, the only other path forward would be for the FDA to create a new and unique set of regulations for FMT and providing stool donors. The fact that we have to offer $1 million per stool to even acquire a donor that meets the ideal criteria makes it even more non-viable. Not to mention that a single donor can’t supply enough “substance” for thousands to millions of people. But if we did get funding we could probably get FMT/”a new drug/biologic” approved.
During the meeting, I was asked if I intended to take down the website. No, I don't. You may just be doing your job, but I am fighting for my life. Unlike the thousands of other patients I've come across who are perfectly willing to sit around and do nothing to help themselves while they suffer and die, I will not have my entire life stolen from me without putting up a fight. I will not voluntarily waste away while an incompetent research system continues to run useless and dangerous clinical trials, and while there's a simple and available cure that no one else is motivated enough to obtain, and which the FDA seems intent on keeping out of patients' reach.
I intend to do what it takes to obtain a currently-existing cure. I don't know what has been put in the drinks of the hundreds of millions of other chronically ill people to make them completely placated and apathetic, but it doesn't appear to have affected me.
I was considering going to protest on the US Capitol steps, but based on what I've experienced so far, there wouldn't even be a peep about it in the news. Just a short note tucked away somewhere in a large stack of papers that "We moved some homeless guy off the steps of the capitol", then "another sick homeless person died in jail".
Additionally, there is no need for me to continue to struggle alone and try to do everything myself. I have come up with a solution that works for me. If you want access to a cure, you will have to help work for it.
It is now up to the research, medical, and patient communities to take action if they want a cure to be available. I've done everything I can, and I won’t keep doing all the work while everyone else sits back and watches.
The FDA may approve FMT tomorrow, or never. It looks like the latter, based on their actions over the past decade.
What would sensible regulation for FMT look like?
It would be based on:
Educating patients so that proper informed consent can occur. Not the sham informed consent occurring in many clinical trials and virtually completely absent in most medical settings. This includes patients being informed about donor quality, and donor quality factors.
Require donor-specific, and source-specific public tracking & reporting of results in a specified, universal format.
Require donor-quality standards that match the current evidence.
Those would be higher standards than any current source of FMT meets, other than Human Microbes. No properly informed patient would accept stool from a former colon cancer patient. They'd ask "Why can't I have stool from someone healthy?". They wouldn't consent to taking antibiotics instead of FMT from a high-quality donor either. And they're currently being forced to do so.
I see one of 3 paths forward:
Someone provides tens of millions of dollars for INDs and clinical trials. This would allow FMT to get approved under the current regulations.
The FDA makes FMT-specific policies that allow a project like this to continue as is. If that occurs, it would be beneficial to partner with one or more people who can take over the business side of things and let everyone know that we have high-quality donors available. Let me know if you’re interested & capable.
Nothing changes and high-quality donors are only available to very wealthy people.
It’s also possible that the FDA takes a middle ground where they approve FMT, but according to drug manufacturing rules, such as requiring it to be manufactured in a lab according to GMP standards. I think this would be inappropriate, and significantly raise the cost for recipients without being any safer. Currently, recipients can order from any of our donors around the world. That may be impossible if drug manufacturing standards were imposed.
Our donors are essentially making and preparing a human-fermented food. Preparing and shipping it as you would with any other homemade food, should be entirely adequate. This is how our donors currently do it.
Other countries:
According to the FDA’s Export Requirements for Unapproved Drugs, we should be able to export stool for FMT to any country if one or more specific countries approve it for marketing. The wording on that page is not clear if it needs approval from all the listed countries or just one of them. But according to the (21 USC § 382) they cite, it’s one/any. So it’s important for regulators in those countries to read these blogs. I’m happy to share the uncensored material with other regulatory agencies.
The business side of things has never been my focus or expertise, so I'm happy to partner with someone with those capabilities. If you think you can run and grow an international company in this field, let me know. If all else fails, it may be possible to switch to selling “a human-fermented food”. But that would require someone with business & marketing expertise to take over.
The results of the FDA’s stance:
I started off with "Is the FDA evil?" in this blog title. I decided against it even though I believe this section successfully proves it. Why? I think it puts too much of the blame on the FDA. The patient community has been absolutely apathetic and wilfully ignorant. And funding has been redirected into much less promising projects. The fact is that the FDA is not the sole entity responsible for preventing a cure from being available. FMT could have been available many years ago if people were well-informed, making intelligent decisions, taking action, and able to acquire funding.
I think the FDA could make a good argument that they're doing their job very well, and the blame lies solely on the entities that fund and run public research. What we can blame the FDA for is not recognizing and acting on the fact that safe & effective FMT from high-quality donors will never be available under the current regulatory framework.
The extremely flawed research system isn't going to provide it. The pharmaceutical industry isn't going to provide it. And the FDA is severely hindering us patients from obtaining it on our own.
It is ultimately FDA policies that are effectively preventing a simple treatment and cure for numerous diseases from ever being available. In a non-dystopian society where people are well-informed and behave rationally, there would be massive outcry about this. But in this one, no one cares.
I see C. diff patients complaining that they've done multiple rounds of a $20,000 drug/probiotic and they still haven't been cured. Yet the FDA says that we can't even provide FMT to them without an IND.
You can look up videos of FDA FMT hearings to see C. diff patients testifying that they would be dead without FMT. These hearings were for the purpose of giving C. diff special status to not require an IND for FMT since it was widely recognized that an IND was too restrictive.
A reasonable thing for the FDA to do would be to allow patients who tried and failed the $20k drug to access our donors instead of just letting the patients die. However, the FDA’s policies have been ensuring that the availability of FMT is extremely limited and that everyone is stuck using low-quality, risky & dangerous donors.
Patients with conditions other than C. diff aren’t even being considered as valid candidates for FMT. The outcome is that millions of people with conditions that are likely curable with FMT continue to needlessly suffer and die.
It appears that the FDA expects me and other patients to sit around wasting away in agony while a cure currently exists. What would you call that? No competent, well-informed person would do that if they were in our position.
If they allow the widespread use of a harmful drug without ensuring the informed consent of patients and then deny access to the only reasonable method to attempt to reverse that damage, what would you call that?
If FDA policy results in a disabled patient who has a few hours per month where they're able to leave the house, having to resort to spending those hours begging strangers on the street for their feces, and then gets worse from using dangerous, low-quality donors due to no other options, while having to spend a decade becoming a world expert in a new medical field, while researching and acquiring their own treatment, successfully figuring out how to identify safe and effective donors, screens over a million people to find one, while meeting standards far higher than any other entity the FDA has approved. And the FDA's response is to deny enforcement discretion, which appears to be exactly for unique situations like this one, and say "Too bad, your journey ends here. Wither and die". What would you call that?
If you dismiss it as merely a rigid bureaucracy unable to adapt to unique situations, would that make it not evil? The definition of “evil” doesn't include intent, so even if they're not deliberately attempting to do harm, the outcome is the same. If the outcome is evil then the FDA is evil.