8 ms·

>One big problem is the FDA's slowness regarding treatments for otherwise fatal diseases like GBM. What do you mean by slowness? They can't skip all the safety

>One big problem is the FDA's slowness regarding treatments for otherwise fatal diseases like GBM. What do you mean by slowness? They can't skip all the safety stuff!

ndr 2y ago
True for _all_ 'safety stuff.' However, safety requirements for late-stage patients with very few other options ought to differ from safety requirements for mass adoption.
- rl3 2y ago
  >However, safety requirements for late-stage patients with very few other options ought to differ from safety requirements for mass adoption. Do they not already?
- vkou 2y ago
  They already do.
deleted 2y ago
[deleted]
emblaegh 2y ago
You seem to imply that the only possible source of slowness if safety, which might not be the case (I've no idea).
advael 2y ago
I mean, if you have an aggressively terminal disease with no known cure, I think the risk-reward calculus is somewhat different from the average drug The issue, as comes up incessantly in all manner of situations, is the way we regulate drugs as a whole. A lack of safety testing should mean a higher standard of informed consent should be used, not that it should be illegal for someone to get ahold of it I see lots of benefit to regulatory agencies controlling what claims can be made about medications and holding people selling them to account for quality control failures. Agencies preventing consenting adults from making their own risk-reward calculations does badly on both principle and outcomes
- scott_w 2y ago
  While I agree that my calculation on safety would be different for a terminal illness for which no cure exists, we still need to be careful. The very nature of this situation creates desperate people who are willing to ignore a simple warning label in favour of hope. Any system / regulator still needs to force companies to prove their treatment has the claimed effect, and block any that simply don't. On safety, I think there's more wiggle room, however. Treatment here can be based on likely ill effects vs the known effects of the illness of the patient.
  - advael 2y ago
    Nah, I actually think the effectiveness standard is far worse than the safety standard due to what a "block" means and how "effectiveness" is tested. An RCT, the gold standard by which medicines are often tested, can easily show a negligible effect size because of the vast confound space of individual differences. A medicine that works perfectly for many of a study's participants will be considered "ineffective" routinely And hey, in cases like that I think the regulators should absolutely have the power to say "selling this without explaining these caveats is criminal fraud", but not that people can't try the drug anyway if informed of the risks and low likelihood of success as determined by the agency's analysis In an effort to standardize process and appease large incumbent industry players (often, as here, by erecting enormous entry barriers in front of lucrative markets), we frequently create metrics that are too blunt and remedies that favor governments flexing disproportionate power over the lives and choices of individuals
    - scott_w 2y ago
      I think this risks creating a perverse incentive where actually creating a cure is hard but looking like you maybe, sometimes, if you squint just right, cure the illness is easy. So companies start to ignore those hard cures in favour of sugar pills with warning labels on.
      - advael 2y ago
        You can already do that though. There's a massive essentially unregulated market full of "supplements" and "alternative medicine" and "faith healing" you can play in if you're dedicated to the business of scamming people who don't look at claims skeptically, including but not limited to people who have terminal diseases. This regulatory process does absolutely nothing to prevent that. However, due to the broad authority of agencies like the FDA and DEA to outlaw drugs that demonstrably do something, we are left with a situation where most of what gets shut down is actual useful medicine
px43 2y ago
Why is it that so many people need to die in the name of safety?
- pompino 2y ago
  Because you can't honestly presume to know the outcome of a clinical trial of an untested product.
  - FeepingCreature 2y ago
    So run the clinical trial, advertise the product as untested and dangerous-to-lethal in the meantime, and let people make their own choices?
    - bartekrutkowski 2y ago
      Smoking is already advertised as dangerous-to-lethal and look how effective it is in preventing people from smoking. In huge oversimplification some crazy or fraudulent people will claim it cures blindness or cold sores, some other people will believe them and will have to deal with the real danger-to-lethal consequences, with the rest of society paying for their medical care afterwards.
      - defrost 2y ago
        > Smoking is already advertised as dangerous-to-lethal and look how effective it is in preventing people from smoking. Pretty effective. In Australia throwing a few diseased lungs on the packs and increasing public awareness has seen usage drop from 35% of the population in 1980 to 11% today. Not all the drop is purely related to advertising, price increases and restricting sale to out of sight locked access in shops have also helped. https://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1-3-prevalence-of-smoking-adults https://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1...
        mewpmewp2 2y ago
evandijk70 2y ago
Not just safety, but also effectiveness. FDA checks whether the trial(s) to prove the drugs effectiveness were run correctly (eg. the randomization, the control group, etc.), if the statistical analysis was done right, if the endpoints are appropriate (response to treatment is not always objective) etc. etc. The FDA (and EMA in Europe) are the only thing that protects desperate patients from fraudsters, charlatans and pharma-companies just looking for a return on their investment.
- wbl 2y ago
  Remember the pandemic? The FDA had safety and effectiveness data by end of August for the vaccine and were unprepared to do an analysis in less than a few months. Nor did they consider drafting the party boys of the Ozarks to get the efficiency data faster. As a result the winter of 2020-2021 saw thousands of preventable deaths. There's also the part where distribution was done in a way that deliberately killed people so that racial equality goals could be met. Perhaps the worst example of this kind of thinking were teachers in SF getting vaccinated but school not starting again.
- bhickey 2y ago
  Ideally this is what would happen. In practice there have been very public failures in being overly cautious and aggressive. While Aduhelm reduces Aβ it has no clinically significant effect. Still, the FDA approved it. Mercifully it'll be discontinued in November. The covid vaccine represented a huge policy failure by the FDA. While people in nursing homes died in droves we got small clinical trials. When you've got 90 year olds in a congregate setting facing a 50% chance of death, maybe it's time to stop pretending thalidomide may be lurking around every corner. The pediatric trials were just as bad. Due to their sizing it was statistically impossible to detect rare adverse effects. Yet, vaccination was delayed for children while these fruitless trials ran. In my own experience I had a low cost, high throughput covid testing protocol ready to go in early April 2020. It took the FDA until August 2020 to provide templates and another month to grant emergency use authorization. We could've drastically ramped up testing when it was needed most of the FDA has treated an emergency like an emergency.
  - 2y ago
ben_w 2y ago
> What do you mean by slowness? They can't skip all the safety stuff! One can be fast and safe, it's just that requires spending a lot of money. It's analogous to cache prefetching and branch prediction in CPUs, except the cost of bad predictions is measured in millions of dollars rather than tens of CPU cycles, and also that the predictions are much harder.
okaram 2y ago
Yes, the system works, and we have very little poison being sold as medicine. The issue is that with some illnesses/stages, we do not have a good treatment, and a lot of people would like the calculus to be different. We do have compassionate drug rules, but they're a pain for many people. I'm not in that situation, and not sure how I'd react; but I can see how, having an incurable illness, with tons of suffering or a few months left to live, I might want to try everything. Hydroxychloroquine, Chinese acupuncture, herbal remedies, and experimental treatments.

>One big problem is the FDA's slowness regarding treatments for otherwise fatal diseases like GBM. What do you mean by slowness? They can't skip all the safety stuff!

ndr 2y ago

True for _all_ 'safety stuff.' However, safety requirements for late-stage patients with very few other options ought to differ from safety requirements for mass adoption.

rl3 2y ago
>However, safety requirements for late-stage patients with very few other options ought to differ from safety requirements for mass adoption. Do they not already?
vkou 2y ago
They already do.

deleted 2y ago

[deleted]

emblaegh 2y ago

You seem to imply that the only possible source of slowness if safety, which might not be the case (I've no idea).

advael 2y ago

I mean, if you have an aggressively terminal disease with no known cure, I think the risk-reward calculus is somewhat different from the average drug The issue, as comes up incessantly in all manner of situations, is the way we regulate drugs as a whole. A lack of safety testing should mean a higher standard of informed consent should be used, not that it should be illegal for someone to get ahold of it I see lots of benefit to regulatory agencies controlling what claims can be made about medications and holding people selling them to account for quality control failures. Agencies preventing consenting adults from making their own risk-reward calculations does badly on both principle and outcomes

scott_w 2y ago
While I agree that my calculation on safety would be different for a terminal illness for which no cure exists, we still need to be careful. The very nature of this situation creates desperate people who are willing to ignore a simple warning label in favour of hope. Any system / regulator still needs to force companies to prove their treatment has the claimed effect, and block any that simply don't. On safety, I think there's more wiggle room, however. Treatment here can be based on likely ill effects vs the known effects of the illness of the patient.
- advael 2y ago
  Nah, I actually think the effectiveness standard is far worse than the safety standard due to what a "block" means and how "effectiveness" is tested. An RCT, the gold standard by which medicines are often tested, can easily show a negligible effect size because of the vast confound space of individual differences. A medicine that works perfectly for many of a study's participants will be considered "ineffective" routinely And hey, in cases like that I think the regulators should absolutely have the power to say "selling this without explaining these caveats is criminal fraud", but not that people can't try the drug anyway if informed of the risks and low likelihood of success as determined by the agency's analysis In an effort to standardize process and appease large incumbent industry players (often, as here, by erecting enormous entry barriers in front of lucrative markets), we frequently create metrics that are too blunt and remedies that favor governments flexing disproportionate power over the lives and choices of individuals
  - scott_w 2y ago
    I think this risks creating a perverse incentive where actually creating a cure is hard but looking like you maybe, sometimes, if you squint just right, cure the illness is easy. So companies start to ignore those hard cures in favour of sugar pills with warning labels on.
    - advael 2y ago
      You can already do that though. There's a massive essentially unregulated market full of "supplements" and "alternative medicine" and "faith healing" you can play in if you're dedicated to the business of scamming people who don't look at claims skeptically, including but not limited to people who have terminal diseases. This regulatory process does absolutely nothing to prevent that. However, due to the broad authority of agencies like the FDA and DEA to outlaw drugs that demonstrably do something, we are left with a situation where most of what gets shut down is actual useful medicine

px43 2y ago

Why is it that so many people need to die in the name of safety?

pompino 2y ago
Because you can't honestly presume to know the outcome of a clinical trial of an untested product.
- FeepingCreature 2y ago
  So run the clinical trial, advertise the product as untested and dangerous-to-lethal in the meantime, and let people make their own choices?
  - bartekrutkowski 2y ago
    Smoking is already advertised as dangerous-to-lethal and look how effective it is in preventing people from smoking. In huge oversimplification some crazy or fraudulent people will claim it cures blindness or cold sores, some other people will believe them and will have to deal with the real danger-to-lethal consequences, with the rest of society paying for their medical care afterwards.
    - defrost 2y ago
      > Smoking is already advertised as dangerous-to-lethal and look how effective it is in preventing people from smoking. Pretty effective. In Australia throwing a few diseased lungs on the packs and increasing public awareness has seen usage drop from 35% of the population in 1980 to 11% today. Not all the drop is purely related to advertising, price increases and restricting sale to out of sight locked access in shops have also helped. https://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1-3-prevalence-of-smoking-adults https://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1...
      - mewpmewp2 2y ago

evandijk70 2y ago

Not just safety, but also effectiveness. FDA checks whether the trial(s) to prove the drugs effectiveness were run correctly (eg. the randomization, the control group, etc.), if the statistical analysis was done right, if the endpoints are appropriate (response to treatment is not always objective) etc. etc. The FDA (and EMA in Europe) are the only thing that protects desperate patients from fraudsters, charlatans and pharma-companies just looking for a return on their investment.

wbl 2y ago
Remember the pandemic? The FDA had safety and effectiveness data by end of August for the vaccine and were unprepared to do an analysis in less than a few months. Nor did they consider drafting the party boys of the Ozarks to get the efficiency data faster. As a result the winter of 2020-2021 saw thousands of preventable deaths. There's also the part where distribution was done in a way that deliberately killed people so that racial equality goals could be met. Perhaps the worst example of this kind of thinking were teachers in SF getting vaccinated but school not starting again.
bhickey 2y ago
Ideally this is what would happen. In practice there have been very public failures in being overly cautious and aggressive. While Aduhelm reduces Aβ it has no clinically significant effect. Still, the FDA approved it. Mercifully it'll be discontinued in November. The covid vaccine represented a huge policy failure by the FDA. While people in nursing homes died in droves we got small clinical trials. When you've got 90 year olds in a congregate setting facing a 50% chance of death, maybe it's time to stop pretending thalidomide may be lurking around every corner. The pediatric trials were just as bad. Due to their sizing it was statistically impossible to detect rare adverse effects. Yet, vaccination was delayed for children while these fruitless trials ran. In my own experience I had a low cost, high throughput covid testing protocol ready to go in early April 2020. It took the FDA until August 2020 to provide templates and another month to grant emergency use authorization. We could've drastically ramped up testing when it was needed most of the FDA has treated an emergency like an emergency.
- 2y ago

ben_w 2y ago

> What do you mean by slowness? They can't skip all the safety stuff! One can be fast and safe, it's just that requires spending a lot of money. It's analogous to cache prefetching and branch prediction in CPUs, except the cost of bad predictions is measured in millions of dollars rather than tens of CPU cycles, and also that the predictions are much harder.

okaram 2y ago

Yes, the system works, and we have very little poison being sold as medicine. The issue is that with some illnesses/stages, we do not have a good treatment, and a lot of people would like the calculus to be different. We do have compassionate drug rules, but they're a pain for many people. I'm not in that situation, and not sure how I'd react; but I can see how, having an incurable illness, with tons of suffering or a few months left to live, I might want to try everything. Hydroxychloroquine, Chinese acupuncture, herbal remedies, and experimental treatments.