8 ms·

Picture the situation: someone you love has just been diagnosed with a death sentence disease with no know treatment. The FDA just chose not to outlaw a promisi

Picture the situation: someone you love has just been diagnosed with a death sentence disease with no know treatment. The FDA just chose not to outlaw a promising but unproven new treatment for it. Now you get to choose whether to take it or not. And somehow the FDA are evil twisted bad guys!?

bedhead 2y ago
I bet the treatment costs somewhere around $350,000. These should be approved on the condition that the patients pay into escrow and get refunded one day if the drug fails trials.
Klinky 2y ago
There's already Expanded Access / Compassionate Care options for terminal patients. It doesn't require the FDA rushing through unproven medications.
jostmey 2y ago
Except that the FDA frequently denies treatments lacking evidence of benefit except in these two cases. The real problem is that it costs too much to bring new treatments through a clinical trial
- derlvative 2y ago
  Except that I don't think the FDA should do that? I'm arguing that people should have options that are not certain death.
  - hmottestad 2y ago
    Not much point researching a better treatment when you can just sell something that doesn't work.
  - cool_dude85 2y ago
    Here's an option: buy cool dude tincture at 10 dollars a bottle instead of this treatment at 10 thousand or whatever.
- Aurornis 2y ago
  The point was that people are up in arms about either outcome: FDA denies approval, people get angry. FDA allows approval, people get angry. > The real problem is that it costs too much to bring new treatments through a clinical trial As opposed to what? Just letting anything go? We basically have that situation in the alternative medicine world and the grifters are out in full force peddling things that we know don’t work the way they claim. Imagine how bad it would be if we waived away clinical trial requirements.
  - michaelt 2y ago
    > The point was that people are up in arms about either outcome: FDA denies approval, people get angry. FDA allows approval, people get angry. What people want is approval through a fair, orderly process. If the tests and reports and expert opinions and panel decisions are needed, their results should be respected - for every drug maker. If the tests and reports &c. aren't needed - they shouldn't be required. If there's some more nuanced approach required, like experimental exceptions for drugs specifically for people who are otherwise terminally ill, it should be codified. The approach of "spend a load of money on studies, then maybe the boss ignores the results" seems very open to corruption.
  - jostmey 2y ago
    Finding ways to reduce the costs of a clinical trial does not mean abandoning clinical trials (or something sufficiently similar)
  - inglor_cz 2y ago
    At the very least, FDA should allow use of medications that were approved in Japan or the EU. Requiring separate US clinical trials is an unnecessary burden for the manufacturer, and will likely result in higher prices or unavailability of some medications. Even in programming we frown upon "reinventing the wheel". This is reinventing the wheel with a fantastic price tag.
otterley 2y ago
The FDA, like other regulatory agencies, exists for a reason: to help prevent people from being ripped off, or worse, by snake oil salesmen. I’d rather we not go back to the days when hucksters and charlatans were selling marked-up dyed water or poison to desperate people out of a horse-drawn carriage.
- derlvative 2y ago
  Completely false comparison because the drug in question did provw safety though the clinical trial, only effectiveness that could not be determined. People should have options that are not certain death.
  - otterley 2y ago
    It’s not a false comparison. Effectiveness is what makes a drug not merely dyed water. Hence the “ripped off” part.
    - fastaguy88 2y ago
      The tricky business is defining effectiveness (and the target population). This drug was not effective at the specified clinical end-point for one set of patients. But it did show promise for other end-points (production of a normal dystrophin transcript). For complex diseases with a range of severities, failing the specified clinical endpoint is not the same as selling dyed water.
      - trehalose 2y ago
        Is production of a normal dystrophin transcript a real clinical endpoint, or just a biomarker that's supposed to correlate for one? It's not immediately obvious how normalizing production of a protein involved in muscle function is beneficial, if it doesn't actually improve muscle function.
        fastaguy88 2y ago
redserk 2y ago
I don't think being in that situation with a line of snake oil salesmen promising their unproven supposed-cures will help here.
hmottestad 2y ago
And your loved one dies of the disease at the exact same time they would otherwise have died of it, but now only after having gone through lots of expensive treatment and suffered a bunch of side effects. The FDA is definitely the evil and twisted bad guys if they can't stop snake oil sellers from stating that their products cure disease X just because the snake oil guy us friends with someone high up in the FDA.
jobs_throwaway 2y ago
Oh no, now I must use my own brain and make the cost-benefit analysis for myself. I wish it was in the hands of some people who neither know nor give a shit about me or my loved one
- kaibee 2y ago
  Desperate parents are well known for their medical expertise and cold logical calculus.
freedomben 2y ago
Personally, I think it's egregious to deny people possible treatments, particularly in cases like that. I think FDA should be very strict on approvals (i.e. giving it that stamp), but should not be gatekeeping people. If people want to take non-FDA approved stuff, I don't see why regulatory and/or law enforcement should care. There's an incredible amount of paternalism inherent in the current system that nobody ever seems to question, and that blows my mind. Now that said, I have a huge problem with this skipping. FDA rules need to be applied consistently and follow the process. I'm sympathetic to the desired outcome, but the problem is the system is set up as a gatekeeper. Fix the system, don't try to hack around it like this. That just further undermines trust and faith in the system.
- tchalla 2y ago
  What’s the best argument you’ve heard against your position about it people taking non-FDA approved stuff?
  - freedomben 2y ago
    well, "best" is subjective, but IMHO the best argument against it is that some companies would skip FDA altogether and try to go direct to market, and would use marketing tactics to undermine faith in the FDA and convince people that the lack of FDA approval doesn't matter. Personally, I do think this would happen, but I think there are better ways to combat this than to use force of law to gatekeep which molecules people are legally allowed to put into their own bodies. We could (and should) still require them to provide evidence for any claims they make, and failure to provide evidence opens them up for liability. There are situations in which paternalism seems justified, but I think in this we've gone way overboard.
    - camel_Snake 2y ago
      AFIAK FDA doesn't regulate what you, yourself, are legally allowed to consume but rather what companies are allowed to market as drugs and legally distribute as such. For example you can bring your own non-FDA approved drugs with you to the US for personal consumption. I found the following document, section 9-2 covers this topic: https://www.fda.gov/media/71776/download?attachment https://www.fda.gov/media/71776/download?attachment
devmor 2y ago
Your imagined situation relies on the supposition that the new treatment is "promising" - how often do you think this is the case? A person facing death from disease is desperate, and desperate people are easily taken advantage of. This is part of the reason the FDA exists - to protect desperate people from being ripped off. The FDA can and should prevent unproven medicines that are not ready for human trials from being used without due diligence.
ooterness 2y ago
No, not "promising but unproven" at all. This drug failed its clinical trial. It got its chance, and the evidence indicates it doesn't work.
n4r9 2y ago
The links from OP are paywalled but the first few visible lines are enough to cast significant doubt for me on whether the treatment is even "promising": > [Sarepta's] gene therapy for Duchenne muscular dystrophy failed to improve muscle function compared to a placebo in a large clinical trial https://www.statnews.com/2023/10/30/sareptas-duchenne-gene-therapy-fails-to-meet-primary-endpoint-in-pivotal-trial/ https://www.statnews.com/2023/10/30/sareptas-duchenne-gene-t... > the drug failed a large, Phase 3 trial last year ... three review teams ... wrote that the data Sarepta submitted "cast significant uncertainty regarding the benefits of the treatment". https://www.statnews.com/2024/06/20/sarepta-duchenne-elevidys-fda-approval-peter-marks-overruled-staff/ https://www.statnews.com/2024/06/20/sarepta-duchenne-elevidy... I'm not sure what makes this treatment "promising" other than the gushings of the CEO. Are you arguing that we should give new treatments a free pass on regulations as long as its for a death-sentence disease and the CEO has connections?
lavelganzu 2y ago
This objection is pure ignorance. "Compassionate use" is already one of the expanded access exceptions, and has been for over 50 years.
actinium226 2y ago
[flagged]
JumpCrisscross 2y ago
Is it illegal to prescribe the molecule off label?
- derlvative 2y ago
  This is a good point. Doctors can prescribe drugs approved for disease X off label to treat disease Y even when effectiveness against Y has not been proven. In this case, the drug has not been approved for any disease so it can't be prescribed. Just goes to show how arbitrary the rules are.
  - radlad 2y ago
    I'm not sure that makes it "arbitrary." Approval is not just about effectiveness but also risks and side effects.
    - JumpCrisscross 2y ago
      If we've gotten to Phase III, the risks and side effects are understood as well as they would be for a doctor prescribing off label. While I might not call it arbitrary, I would say it's an unappreciated edge case.
deleted 2y ago
[deleted]
amluto 2y ago
I’d like to see a payment structure more like a bounty for efficacy. If you think you can cure DMD, you know up-front what you’ll get paid, and it depends on how well it works, dosing schedule, side effects, etc. If your drug is safe but barely works, you get paid a tiny bit of money. If DMD patients’ families want the drug and the manufacturer is willing to sell it at the appropriately low price, fine. IMO the actual failure here is the fact that Sarepta can charge $3.2M for a product without demonstrated efficacy.
makmanalp 2y ago
A customer base of people with profoundly serious troubles at the edge of desperation who are looking for any glimmer of hope. An industry who's incentivized to charge astronomical amounts to an untapped market to recoup costs. A drug that seems to have failed based on multiple trials and 3 separate expert review teams. Now remove the approval requirements. What could possibly go wrong? It's easy to yell paternalism but this doesn't look like a case of paper pushers getting in the way of a promising drug to me. Also, history is littered with examples of why "buyer beware" does NOT work, and a vast literature on information asymmetry, adverse selection, "The Market for Lemons", etc etc. Also, the FDA already has mechanisms to speed up new drugs getting to patients when the benefit is clear early on, AFAIK.
goldpizza44 2y ago
> Now you get to choose whether to take it or not. The question is who is paying for these treatments? Drug companies are not shy about charging tens of thousands of dollars a year for a course of treatment that may or may not help. Insurance companies and Medicare partD will probably be reluctant to reimburse. Drug companies have large incentives to get patients to pay out of pocket, and no, they won't refund if the product is not effective. Perhaps if the FDA were to create a new class of approval that states: Drugs under this class are shown to not cause harm but are also not proven to be helpful. They may be taken, but drug companies may not charge for supplies until efficacy is shown in controlled conditions. The primary issue here is there are plenty of Snake Oil salesmen ready to tell you anything you want to hear and have no qualms about taking "somebody's" money. I am sure creating a new class such as this, will also create a host of unintended consequences though.
pama 2y ago
By awarding approval to an ineffective drug, the FDA reduces competition that could otherwise have led to an effective therapy in the future.

bedhead 2y ago

I bet the treatment costs somewhere around $350,000. These should be approved on the condition that the patients pay into escrow and get refunded one day if the drug fails trials.

Klinky 2y ago

There's already Expanded Access / Compassionate Care options for terminal patients. It doesn't require the FDA rushing through unproven medications.

jostmey 2y ago

Except that the FDA frequently denies treatments lacking evidence of benefit except in these two cases. The real problem is that it costs too much to bring new treatments through a clinical trial

derlvative 2y ago
Except that I don't think the FDA should do that? I'm arguing that people should have options that are not certain death.
- hmottestad 2y ago
  Not much point researching a better treatment when you can just sell something that doesn't work.
- cool_dude85 2y ago
  Here's an option: buy cool dude tincture at 10 dollars a bottle instead of this treatment at 10 thousand or whatever.
Aurornis 2y ago
The point was that people are up in arms about either outcome: FDA denies approval, people get angry. FDA allows approval, people get angry. > The real problem is that it costs too much to bring new treatments through a clinical trial As opposed to what? Just letting anything go? We basically have that situation in the alternative medicine world and the grifters are out in full force peddling things that we know don’t work the way they claim. Imagine how bad it would be if we waived away clinical trial requirements.
- michaelt 2y ago
  > The point was that people are up in arms about either outcome: FDA denies approval, people get angry. FDA allows approval, people get angry. What people want is approval through a fair, orderly process. If the tests and reports and expert opinions and panel decisions are needed, their results should be respected - for every drug maker. If the tests and reports &c. aren't needed - they shouldn't be required. If there's some more nuanced approach required, like experimental exceptions for drugs specifically for people who are otherwise terminally ill, it should be codified. The approach of "spend a load of money on studies, then maybe the boss ignores the results" seems very open to corruption.
- jostmey 2y ago
  Finding ways to reduce the costs of a clinical trial does not mean abandoning clinical trials (or something sufficiently similar)
- inglor_cz 2y ago
  At the very least, FDA should allow use of medications that were approved in Japan or the EU. Requiring separate US clinical trials is an unnecessary burden for the manufacturer, and will likely result in higher prices or unavailability of some medications. Even in programming we frown upon "reinventing the wheel". This is reinventing the wheel with a fantastic price tag.

otterley 2y ago

The FDA, like other regulatory agencies, exists for a reason: to help prevent people from being ripped off, or worse, by snake oil salesmen. I’d rather we not go back to the days when hucksters and charlatans were selling marked-up dyed water or poison to desperate people out of a horse-drawn carriage.

derlvative 2y ago
Completely false comparison because the drug in question did provw safety though the clinical trial, only effectiveness that could not be determined. People should have options that are not certain death.
- otterley 2y ago
  It’s not a false comparison. Effectiveness is what makes a drug not merely dyed water. Hence the “ripped off” part.
  - fastaguy88 2y ago
    The tricky business is defining effectiveness (and the target population). This drug was not effective at the specified clinical end-point for one set of patients. But it did show promise for other end-points (production of a normal dystrophin transcript). For complex diseases with a range of severities, failing the specified clinical endpoint is not the same as selling dyed water.
    - trehalose 2y ago
      Is production of a normal dystrophin transcript a real clinical endpoint, or just a biomarker that's supposed to correlate for one? It's not immediately obvious how normalizing production of a protein involved in muscle function is beneficial, if it doesn't actually improve muscle function.
      - fastaguy88 2y ago

redserk 2y ago

I don't think being in that situation with a line of snake oil salesmen promising their unproven supposed-cures will help here.

hmottestad 2y ago

And your loved one dies of the disease at the exact same time they would otherwise have died of it, but now only after having gone through lots of expensive treatment and suffered a bunch of side effects. The FDA is definitely the evil and twisted bad guys if they can't stop snake oil sellers from stating that their products cure disease X just because the snake oil guy us friends with someone high up in the FDA.

jobs_throwaway 2y ago

Oh no, now I must use my own brain and make the cost-benefit analysis for myself. I wish it was in the hands of some people who neither know nor give a shit about me or my loved one

kaibee 2y ago
Desperate parents are well known for their medical expertise and cold logical calculus.

freedomben 2y ago

Personally, I think it's egregious to deny people possible treatments, particularly in cases like that. I think FDA should be very strict on approvals (i.e. giving it that stamp), but should not be gatekeeping people. If people want to take non-FDA approved stuff, I don't see why regulatory and/or law enforcement should care. There's an incredible amount of paternalism inherent in the current system that nobody ever seems to question, and that blows my mind. Now that said, I have a huge problem with this skipping. FDA rules need to be applied consistently and follow the process. I'm sympathetic to the desired outcome, but the problem is the system is set up as a gatekeeper. Fix the system, don't try to hack around it like this. That just further undermines trust and faith in the system.

tchalla 2y ago
What’s the best argument you’ve heard against your position about it people taking non-FDA approved stuff?
- freedomben 2y ago
  well, "best" is subjective, but IMHO the best argument against it is that some companies would skip FDA altogether and try to go direct to market, and would use marketing tactics to undermine faith in the FDA and convince people that the lack of FDA approval doesn't matter. Personally, I do think this would happen, but I think there are better ways to combat this than to use force of law to gatekeep which molecules people are legally allowed to put into their own bodies. We could (and should) still require them to provide evidence for any claims they make, and failure to provide evidence opens them up for liability. There are situations in which paternalism seems justified, but I think in this we've gone way overboard.
  - camel_Snake 2y ago
    AFIAK FDA doesn't regulate what you, yourself, are legally allowed to consume but rather what companies are allowed to market as drugs and legally distribute as such. For example you can bring your own non-FDA approved drugs with you to the US for personal consumption. I found the following document, section 9-2 covers this topic: https://www.fda.gov/media/71776/download?attachment https://www.fda.gov/media/71776/download?attachment

devmor 2y ago

Your imagined situation relies on the supposition that the new treatment is "promising" - how often do you think this is the case? A person facing death from disease is desperate, and desperate people are easily taken advantage of. This is part of the reason the FDA exists - to protect desperate people from being ripped off. The FDA can and should prevent unproven medicines that are not ready for human trials from being used without due diligence.

ooterness 2y ago

No, not "promising but unproven" at all. This drug failed its clinical trial. It got its chance, and the evidence indicates it doesn't work.

n4r9 2y ago

The links from OP are paywalled but the first few visible lines are enough to cast significant doubt for me on whether the treatment is even "promising": > [Sarepta's] gene therapy for Duchenne muscular dystrophy failed to improve muscle function compared to a placebo in a large clinical trial https://www.statnews.com/2023/10/30/sareptas-duchenne-gene-therapy-fails-to-meet-primary-endpoint-in-pivotal-trial/ https://www.statnews.com/2023/10/30/sareptas-duchenne-gene-t... > the drug failed a large, Phase 3 trial last year ... three review teams ... wrote that the data Sarepta submitted "cast significant uncertainty regarding the benefits of the treatment". https://www.statnews.com/2024/06/20/sarepta-duchenne-elevidys-fda-approval-peter-marks-overruled-staff/ https://www.statnews.com/2024/06/20/sarepta-duchenne-elevidy... I'm not sure what makes this treatment "promising" other than the gushings of the CEO. Are you arguing that we should give new treatments a free pass on regulations as long as its for a death-sentence disease and the CEO has connections?

lavelganzu 2y ago

This objection is pure ignorance. "Compassionate use" is already one of the expanded access exceptions, and has been for over 50 years.

actinium226 2y ago

[flagged]

JumpCrisscross 2y ago

Is it illegal to prescribe the molecule off label?

derlvative 2y ago
This is a good point. Doctors can prescribe drugs approved for disease X off label to treat disease Y even when effectiveness against Y has not been proven. In this case, the drug has not been approved for any disease so it can't be prescribed. Just goes to show how arbitrary the rules are.
- radlad 2y ago
  I'm not sure that makes it "arbitrary." Approval is not just about effectiveness but also risks and side effects.
  - JumpCrisscross 2y ago
    If we've gotten to Phase III, the risks and side effects are understood as well as they would be for a doctor prescribing off label. While I might not call it arbitrary, I would say it's an unappreciated edge case.

deleted 2y ago

[deleted]

amluto 2y ago

I’d like to see a payment structure more like a bounty for efficacy. If you think you can cure DMD, you know up-front what you’ll get paid, and it depends on how well it works, dosing schedule, side effects, etc. If your drug is safe but barely works, you get paid a tiny bit of money. If DMD patients’ families want the drug and the manufacturer is willing to sell it at the appropriately low price, fine. IMO the actual failure here is the fact that Sarepta can charge $3.2M for a product without demonstrated efficacy.

makmanalp 2y ago

A customer base of people with profoundly serious troubles at the edge of desperation who are looking for any glimmer of hope. An industry who's incentivized to charge astronomical amounts to an untapped market to recoup costs. A drug that seems to have failed based on multiple trials and 3 separate expert review teams. Now remove the approval requirements. What could possibly go wrong? It's easy to yell paternalism but this doesn't look like a case of paper pushers getting in the way of a promising drug to me. Also, history is littered with examples of why "buyer beware" does NOT work, and a vast literature on information asymmetry, adverse selection, "The Market for Lemons", etc etc. Also, the FDA already has mechanisms to speed up new drugs getting to patients when the benefit is clear early on, AFAIK.

goldpizza44 2y ago

> Now you get to choose whether to take it or not. The question is who is paying for these treatments? Drug companies are not shy about charging tens of thousands of dollars a year for a course of treatment that may or may not help. Insurance companies and Medicare partD will probably be reluctant to reimburse. Drug companies have large incentives to get patients to pay out of pocket, and no, they won't refund if the product is not effective. Perhaps if the FDA were to create a new class of approval that states: Drugs under this class are shown to not cause harm but are also not proven to be helpful. They may be taken, but drug companies may not charge for supplies until efficacy is shown in controlled conditions. The primary issue here is there are plenty of Snake Oil salesmen ready to tell you anything you want to hear and have no qualms about taking "somebody's" money. I am sure creating a new class such as this, will also create a host of unintended consequences though.

pama 2y ago

By awarding approval to an ineffective drug, the FDA reduces competition that could otherwise have led to an effective therapy in the future.