I do see that as a string argument, but i still think drugs should only go to market legally when both safety and efficacy has been proven in well enough powered RCTs. The risk to the medical profession and the reputation of the drug production industry is just too high to allow any less i think. There’s no reason a fast tracked RCT couldn’t get this sorted in a year and that seems like a reasonable way forward.
The RCT should also be vs. tryptans and not vs. placebo. I’m not sure why the previous small trials were not done vs. standard best practice, that seems odd to me?
If I was sitting in the FDA reviewing this i would still be pretty nervous about making an exception.
It is wonderful to not know what a cluster headache feels like. For to feel a single attack is to know what is one of the greatest tragedies humanity has ever faced.
If these approached anything even 10x worse than the worst pain I’ve ever felt, I might agree with you. Sadly this is not our world. There is no way to understand what a cluster headache feels like without experiencing one.
If it took an FDA approved RCT to get a family member free from torture I would not wait. And if it was illegal or broke FDA norms that would not stop me.
A ‘fast-tracked year’ ignores the shockingly high regulatory burden. For DMT, a Schedule I substance, delivered via an unvalidated inhaler requiring parallel FDA device review, tested against an active comparator which demands larger sample sizes, in a rare disease where existing trials took years to recruit 10-16 patients: year one gets you DEA licensing, device validation, and perhaps your first enrollees. A fast tracked timeline to complete a well-powered RCT—just the trial, just the data— may be something like 3-5 years. And that’s not approval. That’s permission to begin the approval process, which multiplies the timeline again: Phase 3 confirmation, FDA review, DEA rescheduling, state-level legal changes. A record setting entire process might be 5-10 years at minimum before a prescription could be written. The MDMA program had Breakthrough designation, $130 million, two favorable Phase 3 trials, twenty years—and got rejected last August. This problem deserves a novel solution.
You are absolutely right that until an FDA approved product exists that can be recommended by doctors who also rely on RCTs, we cannot expect this problem to go away. May we work to help any RCT become possible. And until that happens, every intervention with evidence as promising as DMT deserves to be accessible, or at the very least not illegal.
First..”If it took an FDA approved RCT to get a family member free from torture I would not wait. And if it was illegal or broke FDA norms that would not stop me.”
I agree with this. even if it might be placebo if a family member was this convinced of something working, I would probably get it for them illegally. This isn’t related by my lights to the question of following proper process.
Second.. “suffering exists on an exponential scale, and these truly represent the end of this spectrum. This is an affliction worse than torture. Survivors of both have said cluster headaches were worse.”
this is a tragedy for sure but I think we have to be careful not to make arguments like this is the only situation where delay causes lots of suffering.
recently a malaria vaccine rollout sat waiting a while for FDA approval. every day delay the might have cost tens of lives (just a guess). I’m not saying waiting for FDA approval is the best situation, but this is not a special case, tragic delays happen all the time.
Upon learning of a tragedy, one response is to note other similar tragedies, say it “happens all the time”, and accept it.
The world’s most painful disease has what appears to be an effective treatment. It cannot be prescribed. It is illegal to try. I work backwards from the view that this is not acceptable.
The rules we create for our society are not set in stone. We can demand that our governments recognize the extremes of suffering.
Three societal frameworks fail to account for something so terrible as a cluster headache.
The first is our criminal legal system. DMT is a Schedule I substance, classified as having “no accepted medical use”. This makes it illegal to possess or administer regardless of medical intent. We are asked to trust that DEA scheduling decisions correctly identify which substances should be categorically forbidden.
The second is our medical regulatory system. The FDA requires rigorous evidence of safety and efficacy before a treatment can enter medical practice. This system asks us to trust that these evidentiary barriers, however expensive and lengthy to clear, are necessary protections.
The third are the economic structures that determine which treatments get developed. Pharmaceutical companies invest in the multi-million dollar studies the FDA requires only when they can expect sufficient returns. Insurance will pay millions to save a life yet almost nothing to prevent extreme suffering.
Where an effective treatment is illegal to obtain, impossible to prescribe, and not incentivized to develop, we find a massive failure. Insurers should pay for preventing extreme suffering the way they pay for extending life. The RCTs would pay for themselves.
And until then, patients should not be criminals for seeking relief from the most painful disease known to medicine.
I do see that as a string argument, but i still think drugs should only go to market legally when both safety and efficacy has been proven in well enough powered RCTs. The risk to the medical profession and the reputation of the drug production industry is just too high to allow any less i think. There’s no reason a fast tracked RCT couldn’t get this sorted in a year and that seems like a reasonable way forward.
The RCT should also be vs. tryptans and not vs. placebo. I’m not sure why the previous small trials were not done vs. standard best practice, that seems odd to me?
If I was sitting in the FDA reviewing this i would still be pretty nervous about making an exception.
It is wonderful to not know what a cluster headache feels like. For to feel a single attack is to know what is one of the greatest tragedies humanity has ever faced.
If these approached anything even 10x worse than the worst pain I’ve ever felt, I might agree with you. Sadly this is not our world. There is no way to understand what a cluster headache feels like without experiencing one.
Suffering exists on an exponential scale, and these truly represent the end of this spectrum. This is an affliction that can be understood as worse than torture — the only pain that routinely scores 10⁄10 in comparative studies.
If it took an FDA approved RCT to get a family member free from torture I would not wait. And if it was illegal or broke FDA norms that would not stop me.
A ‘fast-tracked year’ ignores the shockingly high regulatory burden. For DMT, a Schedule I substance, delivered via an unvalidated inhaler requiring parallel FDA device review, tested against an active comparator which demands larger sample sizes, in a rare disease where existing trials took years to recruit 10-16 patients: year one gets you DEA licensing, device validation, and perhaps your first enrollees. A fast tracked timeline to complete a well-powered RCT—just the trial, just the data— may be something like 3-5 years. And that’s not approval. That’s permission to begin the approval process, which multiplies the timeline again: Phase 3 confirmation, FDA review, DEA rescheduling, state-level legal changes. A record setting entire process might be 5-10 years at minimum before a prescription could be written. The MDMA program had Breakthrough designation, $130 million, two favorable Phase 3 trials, twenty years—and got rejected last August. This problem deserves a novel solution.
You are absolutely right that until an FDA approved product exists that can be recommended by doctors who also rely on RCTs, we cannot expect this problem to go away. May we work to help any RCT become possible. And until that happens, every intervention with evidence as promising as DMT deserves to be accessible, or at the very least not illegal.
why does it take years to recruit as small number of patients if sufferers are so enthusiastic about this as a potential treatment?
First..”If it took an FDA approved RCT to get a family member free from torture I would not wait. And if it was illegal or broke FDA norms that would not stop me.”
I agree with this. even if it might be placebo if a family member was this convinced of something working, I would probably get it for them illegally. This isn’t related by my lights to the question of following proper process.
Second.. “suffering exists on an exponential scale, and these truly represent the end of this spectrum. This is an affliction worse than torture. Survivors of both have said cluster headaches were worse.”
this is a tragedy for sure but I think we have to be careful not to make arguments like this is the only situation where delay causes lots of suffering.
recently a malaria vaccine rollout sat waiting a while for FDA approval. every day delay the might have cost tens of lives (just a guess). I’m not saying waiting for FDA approval is the best situation, but this is not a special case, tragic delays happen all the time.
Upon learning of a tragedy, one response is to note other similar tragedies, say it “happens all the time”, and accept it.
The world’s most painful disease has what appears to be an effective treatment. It cannot be prescribed. It is illegal to try. I work backwards from the view that this is not acceptable.
The rules we create for our society are not set in stone. We can demand that our governments recognize the extremes of suffering.
Three societal frameworks fail to account for something so terrible as a cluster headache.
The first is our criminal legal system. DMT is a Schedule I substance, classified as having “no accepted medical use”. This makes it illegal to possess or administer regardless of medical intent. We are asked to trust that DEA scheduling decisions correctly identify which substances should be categorically forbidden.
The second is our medical regulatory system. The FDA requires rigorous evidence of safety and efficacy before a treatment can enter medical practice. This system asks us to trust that these evidentiary barriers, however expensive and lengthy to clear, are necessary protections.
The third are the economic structures that determine which treatments get developed. Pharmaceutical companies invest in the multi-million dollar studies the FDA requires only when they can expect sufficient returns. Insurance will pay millions to save a life yet almost nothing to prevent extreme suffering.
Where an effective treatment is illegal to obtain, impossible to prescribe, and not incentivized to develop, we find a massive failure. Insurers should pay for preventing extreme suffering the way they pay for extending life. The RCTs would pay for themselves.
And until then, patients should not be criminals for seeking relief from the most painful disease known to medicine.