In what way does the Montana law make snake oil salesmanship hard? Why can't a bad actor just repeatedly file INDs, go through Phase 1 (soon will be close to trivial given AI-enabled drug discovery/design), then sell to unsuspecting consumers as a panacea, then rinse and repeat?
Well that'll be a pretty sophisticated scheme, requiring $5-10m funding per phase-1 trial. I suppose that's possible but it would be a highly legible scheme.
Also what would be the bad outcomes here? If those drugs end up not being safe (that is prevented by the requirement to not withhold safety data), or being effective?
If effectiveness is what you're thinking of, keep in mind things like off-label are already allowed, so even in the current system you have drugs that aren't proven effective for what they're used and we don't call the physicians that prescribe off-label bad actors necessarily.
> Also what would be the bad outcomes here? If those drugs end up not being safe (that is prevented by the requirement to not withhold safety data), or being effective?
Barring a time machine, safety data reporting is gonna lag at least some of the bad outcomes.
But there are, obviously, proportionally way fewer bad outcomes created by drugs that pass Phases 2 and 3 than those that only pass Phase 1. The steepness of that attrition is literally the entire value prop of the law to begin with.
In what way would it be legible? It would look identical to exactly what the Montana law is designed to produce: more drugs that aren't known to work being released to patients. Obviously a large number of those will end up actually not working (which is why trial failure rates are so high to begin with).
Producing $5-10MM in revenue with a snake oil drug strikes me as trivial.
And keep in mind a substantial portion of the Phase 1 + IND costs are incurred in preparation of actually trying to bring a drug fully to market. If your approach is just to Phase 1, milk consumers, then bail, I'm quite confident you can do this much much much more cheaply.
> Also what would be the bad outcomes here? If those drugs end up not being safe (that is prevented by the requirement to not withhold safety data), or being effective?
A requirement not to withhold safety data is different (and easier to enforce at Phase 1) than a requirement to produce the relevant safety data in the first place. Again, designing a Phase 1 study with no ambition to succeed in Phase 2 and Phase 3 will both enable and incentivize a lot more "creativity" in study design to not detect a problem early on. Whereas today, all incentives are aligned toward detecting problems as early as possible, because finding out your drug is unsafe at Phase 3 is financially very bad.
Is the scheme you describe a risk? Sure. Any new mechanism is, until it has a track record.
What I meant by legible: to run it, you'd have to pass FDA's IND review and reporting requirements, IRB review of the Phase 1, and then Montana ETRB review, with public annual outcome reporting and no withholding of safety data from patients. That's a high bar.
If your view is that nothing short of full approval is enough of a bar and no alternative should be tried even at small scale, fine. We should agree to disagree here then.
No, that’s not my belief and it frankly reads as a little petulant.
The risk I’m pointing out has nothing to do with a track record. It’s a design problem. Implementing solutions that are knowably bad is actually really stupid and we shouldn’t do it.
They're absolutely trivial compared to Phases 2 and 3, and part of the cost/complexity of Phase 1 is self-incurred because it's to the company's advantage to detect problems as early as possible. Remove that incentive (because they don't plan to pursue Phase 2, 3, or clearance), and it becomes much cheaper and easier to run broken Phase 1s.
Are you sure about that? I've not run a phase-1 but I'm often told the CMC is the most gnarly and expensive part of it & its due to requirements, not sponsor choices.
If you don’t need to make a drug that actually works, you can choose to make drugs that are very easy to produce instead, therefore CMC becomes way way way simpler.
The FDA does not let you put something in humans without a significant amount of data, full stop. And even for a small trial, the cost of the GLP tox and the GMP manufacturing is in the millions.
Of course it is nowhere near as complex as phase 2. But it is not remotely trivial.
estearum · · focus · HN ↗
niklas_anzinger · · focus · HN ↗
Also what would be the bad outcomes here? If those drugs end up not being safe (that is prevented by the requirement to not withhold safety data), or being effective?
If effectiveness is what you're thinking of, keep in mind things like off-label are already allowed, so even in the current system you have drugs that aren't proven effective for what they're used and we don't call the physicians that prescribe off-label bad actors necessarily.
ceejayoz · · focus · HN ↗
Barring a time machine, safety data reporting is gonna lag at least some of the bad outcomes.
niklas_anzinger · · focus · HN ↗
ceejayoz · · focus · HN ↗
niklas_anzinger · · focus · HN ↗
estearum · · focus · HN ↗
estearum · · focus · HN ↗
Producing $5-10MM in revenue with a snake oil drug strikes me as trivial.
And keep in mind a substantial portion of the Phase 1 + IND costs are incurred in preparation of actually trying to bring a drug fully to market. If your approach is just to Phase 1, milk consumers, then bail, I'm quite confident you can do this much much much more cheaply.
> Also what would be the bad outcomes here? If those drugs end up not being safe (that is prevented by the requirement to not withhold safety data), or being effective?
A requirement not to withhold safety data is different (and easier to enforce at Phase 1) than a requirement to produce the relevant safety data in the first place. Again, designing a Phase 1 study with no ambition to succeed in Phase 2 and Phase 3 will both enable and incentivize a lot more "creativity" in study design to not detect a problem early on. Whereas today, all incentives are aligned toward detecting problems as early as possible, because finding out your drug is unsafe at Phase 3 is financially very bad.
niklas_anzinger · · focus · HN ↗
What I meant by legible: to run it, you'd have to pass FDA's IND review and reporting requirements, IRB review of the Phase 1, and then Montana ETRB review, with public annual outcome reporting and no withholding of safety data from patients. That's a high bar.
If your view is that nothing short of full approval is enough of a bar and no alternative should be tried even at small scale, fine. We should agree to disagree here then.
estearum · · focus · HN ↗
The risk I’m pointing out has nothing to do with a track record. It’s a design problem. Implementing solutions that are knowably bad is actually really stupid and we shouldn’t do it.
colingauvin · · focus · HN ↗
estearum · · focus · HN ↗
niklas_anzinger · · focus · HN ↗
estearum · · focus · HN ↗
Excellent example of precisely my point.
colingauvin · · focus · HN ↗
Of course it is nowhere near as complex as phase 2. But it is not remotely trivial.
estearum · · focus · HN ↗
I’m saying that the millions of dollars in expenses are irrelevant if you can recoup those costs plus some profit by selling snake oil.
Your comment is just “millions of dollars is a lot of money!” I don’t care whether you think that’s a lot of money.
If you think that cost cannot be recouped by selling snake oil for some reason, then explain why.
[deleted] · · focus · HN ↗
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