5 ms·

This is a good thing. People die, and die sooner, when the FDA cannot adapt its approval process to drugs and tools for patients who sadly have little downside

This is a good thing. People die, and die sooner, when the FDA cannot adapt its approval process to drugs and tools for patients who sadly have little downside to trying them. In my own little corner (diabetes) it’s been nice to get monitoring tools earlier than they once would have been approved, and for my medical team to confidently plan for equipment changes based on future approvals.

olliej 7y ago
The problem is the approval of drugs that don’t actually work, and so are actually harmful. the approval then means that companies can target people who are desperate with extremely expensive snake oil. The victims of this have no recourse if/when the drug has caused problems.
- cobbzilla 7y ago
  You’re mixing two things: Doesn’t work = efficacy trials Is harmful = safety trials iirc the safety trials come first. A lot of drugs get stalled in efficacy trials because they might only work for some patients and the sample set is small or poorly chosen. I see no reason to stall drugs that are proven safe, even if they might not be effective for all patients, as long as there is full disclosure and informed consent. Freedom to choose is a good thing.
  - lightedman 7y ago
    "You’re mixing two things:" Being ineffective can be very dangerous as a person taking a drug expecting it to alleviate their condition finds no relief and thus dies from their condition. You did not fully read and comprehend the parent post.
    - cobbzilla 7y ago
      Post implied fairly plainly that “doesn’t work == harmful”, is there another way to read that?
    - kurthr 7y ago
      While I agree with you... if you take the side of the Medical and Insurance industry, it works great. Money is extracted before they died with a high margin process. The incentive is perverse, but it's real and effective.
  - nvrspyx 7y ago
    FDA approves drugs following Phase III Phase I determines safety. Phase II determines efficacy. Phase III is larger scale, randomized, and blind to give the FDA more information on the range of potential adverse effects and the effectiveness of the drug. FDA is supposed to care about both. The acceptable safety of a drug is relative to the effectiveness of it (i.e. a drug may be more dangerous or have more adverse effects, but it’s deemed “worth it” due to the effectiveness of the drug while of course maintaining a minimum safety risk for all drugs). In other words, both safety and effectiveness are both supposed to be taken as equal halves of the whole by the FDA.
    - AnthonyMouse 7y ago
      But you also want to consider alternatives. If you have something which is only effective for a small percentage of people even though it's really dangerous, that may still be worth it as something to use for people for which existing treatments were ineffective and the remaining alternative is certain death. Saving 15% of those people can be better than none.
  - vkou 7y ago
    > I see no reason to stall drugs that are proven safe, even if they might not be effective for all patients, as long as there is full disclosure and informed consent. Freedom to choose is a good thing. I do. For every treatment you are taking, you could have been taking some other treatment that might be more effective. If we have no idea whether or not a drug is more effective than placebo, we should not be administering it.
    - jcims 7y ago
      This perspective is very frustrating to me. Why in the world would a sane person take a drug with unproven efficacy when others with proven efficacy are available? However, there are many cases where there is no alternative drug or treatment that has been tested for efficacy, and so you’re stuck with hospice as standard of care. It’s one thing for a doctor to recommend administration of a medication, it’s another thing entirely to make it unavailable for those that are in a position to make the choice for themselves.
      - vkou 7y ago
        > This perspective is very frustrating to me. Why in the world would a sane person take a drug with unproven efficacy when others with proven efficacy are available? Because they don't want the side effects of proven treatments, and they hope that snake oil will help them. If people were rational about their health, homeopathic supplements, and other similar bullshit wouldn't be a billion dollar industry. If you can't prove that your treatment works, you shouldn't be advertising it as a medical treatment. Advertise it as a non-medical non-treatment.
- s1artibartfast 7y ago
  There is obviously a tradeoff between risk and speed. The article provides evidence that speed is increasing. I don't think the article provides any compelling argument that approvals are too fast. Do you? I thought the FDA summed it it up well in the article: >“We would expect every once in a while that we would be wrong,” with an accelerated approval, she said. “Otherwise, we aren’t taking any chances, we are still making them wait too long to get their hands on this therapy that will extend their lives.”
  - hannob 7y ago
    > There is obviously a tradeoff between risk and speed. The article provides evidence that speed is increasing. I don't think the article provides any compelling argument that approvals are too fast. Do you? Vinay Prasad is a cancer expert and an outspoken critic of too fast approvals of drugs. He has done research on it, I could e.g. find this: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2463590 https://jamanetwork.com/journals/jamainternalmedicine/fullar...
    - s1artibartfast 7y ago
      Im not familiar with his work, but from what you posted, it seems Prasad takes issue with the use of surrogate end points in trials, not fast track approvals. I tend to agree that surrogates and bio markers are a huge problem, but think they are a necessary evil. Drug development would screech to a halt if developers had to wait another 4-5 years for survival data. What we need is more Pase 4 postmarket trials with direct endpoints. Interestingly, the paper linked shows that in some respects, fast tracked drugs have a better track reccord. This shouldnt be surprising as the best drugs are fast tracked. >18 drugs failed to improve overall survival (in 6 of 15 accelerated approvals and in 12 of 21 traditional approvals)
    - robbseaton 7y ago
      Is the FDA Too Conservative or Too Aggressive?: A Bayesian Decision Analysis of Clinical Trial Design The results for conventional fixed-sample randomized clinical-trial designs suggest that for terminal illnesses with no existing therapies such as pancreatic cancer, the standard threshold of 2.5% is substantially more conservative than the BDA-optimal threshold of 27.9%. However, for relatively less deadly conditions such as prostate cancer, 2.5% is more risk-tolerant or aggressive than the BDA-optimal threshold of 1.2%. We compute BDA-optimal sizes for 25 of the most lethal diseases and show how a BDA-informed approval process can incorporate all stakeholders’ views in a systematic, transparent, internally consistent, and repeatable manner. https://www.nber.org/papers/w21499 https://www.nber.org/papers/w21499
Retric 7y ago
Only a fraction of drugs treat life threatening condition in some new way. Painkillers for example represent a surprising fraction of all drugs and generally have a close equivalent. https://www.drugs.com/condition/pain.html https://www.drugs.com/condition/pain.html Taking enough time to endure a new acne medication or Viagra alternative etc is reasonably safe is very much worth spending some extra time. Edit: This does seem to be focused on needed medications without close equivalents but that’s a fairly arbitrary line.
- 1123581321 7y ago
  It is as long as the FDA can operate flexibly enough to not spend extra time where they shouldn’t. If they can’t, as seems to have been the case historically, then it’s best overall from a mortality and longevity perspective if they err on the side of faster releases. Note that faster operation also means they can more quickly act on feedback from the market and medical practitioners post release.
- tpmoney 7y ago
  Close equivalent can still be something you can't take. For example, if you're one of the unfortunate people with no activity on your CYP2D6 enzyme, there are essentially 4 pain medications that you can take at appropriate doses once you need something stronger than advil: Morphine, Dilaudid, Oxymorphone and Fentanyl, and there are reasons why doctors prefer other narcotics before prescribing any of those 4. Other pain medications will work, but you'll likely need inappropriately higher doses[0], which can lead to other problems (like overdosing). Likewise if you process faster than a normal person (i.e. you have more activity on that enzyme) you can overdose at normal prescribing doses. Close equivalents for some people can indeed be the difference between life and death, even if the condition itself isn't life threatening. [0]: https://www.ncbi.nlm.nih.gov/books/NBK100662/ https://www.ncbi.nlm.nih.gov/books/NBK100662/
  - Retric 7y ago
    That’s a very good point, but then we are talking about edge cases and a delay measured in weeks to months. So, the benefit from catching 1 bad drug could outweigh the benefits from releasing 100 drugs slightly earlier. It’s not an easy choice, especially when the risks are often hypothetical and the benefits so clear. It’s interesting looking at lists like this and considering where things broken down. https://en.m.wikipedia.org/wiki/List_of_withdrawn_drugs https://en.m.wikipedia.org/wiki/List_of_withdrawn_drugs
StacyRoberts 7y ago
We need to allow people to self care so you can hack your own diabetes. I wish I could buy my own life sustaining hormone that I've been using for 20 years and understand better than most doctors outside endocrinology.
- big_chungus 7y ago
  I have a friend who has to regularly go to Europe to replace her implantable pump. It's not approved in America because the bureaucrats haven't gotten around to it. So long as there's no false advertising, let people try treatments that work for them, even if there's risk. Said friend has enough money that she's okay, but most others aren't so lucky.
  - StacyRoberts 7y ago
    I dated someone with an external pump. It came off one day and caused so many problems. Just slid from sitting on the couch to the floor watching tv and the cushion caught the pump and broke it off. I immediately thought that type of failure should be recoverable without a hospital visit and surgery and tried to figure out why it wasn't. My mind immediately set to making it so and was held back by the fear I could go to prison for practicing medicine without a license. "I love you. I wish I could fix you. I could fix you." "I know you could. I wish you could."
    - ntdb 7y ago
      [T1D who used an external Medtronic pump for years here] Normally that kind of failure would be quickly recoverable without a hospital visit/surgery, I’m sorry that this one was not.
    - deleted 7y ago
      [deleted]
    - ng12 7y ago
      There are some other options. I use a pump (OmniPod) that is entirely attached to my body. There's a small plastic pod that's taped to the skin and operated wirelessly. My chief complaint is that the FDA is overly restrictive. They force manufacturers to make the products expire earlier to head off concerns about them working less efficiently near the end of the cycle. Diabetes is a disease who's treatment is entirely about guesstimating but the FDA does not take that into account when approving devices.

olliej 7y ago

The problem is the approval of drugs that don’t actually work, and so are actually harmful. the approval then means that companies can target people who are desperate with extremely expensive snake oil. The victims of this have no recourse if/when the drug has caused problems.

cobbzilla 7y ago
You’re mixing two things: Doesn’t work = efficacy trials Is harmful = safety trials iirc the safety trials come first. A lot of drugs get stalled in efficacy trials because they might only work for some patients and the sample set is small or poorly chosen. I see no reason to stall drugs that are proven safe, even if they might not be effective for all patients, as long as there is full disclosure and informed consent. Freedom to choose is a good thing.
- lightedman 7y ago
  "You’re mixing two things:" Being ineffective can be very dangerous as a person taking a drug expecting it to alleviate their condition finds no relief and thus dies from their condition. You did not fully read and comprehend the parent post.
  - cobbzilla 7y ago
    Post implied fairly plainly that “doesn’t work == harmful”, is there another way to read that?
  - kurthr 7y ago
    While I agree with you... if you take the side of the Medical and Insurance industry, it works great. Money is extracted before they died with a high margin process. The incentive is perverse, but it's real and effective.
- nvrspyx 7y ago
  FDA approves drugs following Phase III Phase I determines safety. Phase II determines efficacy. Phase III is larger scale, randomized, and blind to give the FDA more information on the range of potential adverse effects and the effectiveness of the drug. FDA is supposed to care about both. The acceptable safety of a drug is relative to the effectiveness of it (i.e. a drug may be more dangerous or have more adverse effects, but it’s deemed “worth it” due to the effectiveness of the drug while of course maintaining a minimum safety risk for all drugs). In other words, both safety and effectiveness are both supposed to be taken as equal halves of the whole by the FDA.
  - AnthonyMouse 7y ago
    But you also want to consider alternatives. If you have something which is only effective for a small percentage of people even though it's really dangerous, that may still be worth it as something to use for people for which existing treatments were ineffective and the remaining alternative is certain death. Saving 15% of those people can be better than none.
- vkou 7y ago
  > I see no reason to stall drugs that are proven safe, even if they might not be effective for all patients, as long as there is full disclosure and informed consent. Freedom to choose is a good thing. I do. For every treatment you are taking, you could have been taking some other treatment that might be more effective. If we have no idea whether or not a drug is more effective than placebo, we should not be administering it.
  - jcims 7y ago
    This perspective is very frustrating to me. Why in the world would a sane person take a drug with unproven efficacy when others with proven efficacy are available? However, there are many cases where there is no alternative drug or treatment that has been tested for efficacy, and so you’re stuck with hospice as standard of care. It’s one thing for a doctor to recommend administration of a medication, it’s another thing entirely to make it unavailable for those that are in a position to make the choice for themselves.
    - vkou 7y ago
      > This perspective is very frustrating to me. Why in the world would a sane person take a drug with unproven efficacy when others with proven efficacy are available? Because they don't want the side effects of proven treatments, and they hope that snake oil will help them. If people were rational about their health, homeopathic supplements, and other similar bullshit wouldn't be a billion dollar industry. If you can't prove that your treatment works, you shouldn't be advertising it as a medical treatment. Advertise it as a non-medical non-treatment.
s1artibartfast 7y ago
There is obviously a tradeoff between risk and speed. The article provides evidence that speed is increasing. I don't think the article provides any compelling argument that approvals are too fast. Do you? I thought the FDA summed it it up well in the article: >“We would expect every once in a while that we would be wrong,” with an accelerated approval, she said. “Otherwise, we aren’t taking any chances, we are still making them wait too long to get their hands on this therapy that will extend their lives.”
- hannob 7y ago
  > There is obviously a tradeoff between risk and speed. The article provides evidence that speed is increasing. I don't think the article provides any compelling argument that approvals are too fast. Do you? Vinay Prasad is a cancer expert and an outspoken critic of too fast approvals of drugs. He has done research on it, I could e.g. find this: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2463590 https://jamanetwork.com/journals/jamainternalmedicine/fullar...
  - s1artibartfast 7y ago
    Im not familiar with his work, but from what you posted, it seems Prasad takes issue with the use of surrogate end points in trials, not fast track approvals. I tend to agree that surrogates and bio markers are a huge problem, but think they are a necessary evil. Drug development would screech to a halt if developers had to wait another 4-5 years for survival data. What we need is more Pase 4 postmarket trials with direct endpoints. Interestingly, the paper linked shows that in some respects, fast tracked drugs have a better track reccord. This shouldnt be surprising as the best drugs are fast tracked. >18 drugs failed to improve overall survival (in 6 of 15 accelerated approvals and in 12 of 21 traditional approvals)
  - robbseaton 7y ago
    Is the FDA Too Conservative or Too Aggressive?: A Bayesian Decision Analysis of Clinical Trial Design The results for conventional fixed-sample randomized clinical-trial designs suggest that for terminal illnesses with no existing therapies such as pancreatic cancer, the standard threshold of 2.5% is substantially more conservative than the BDA-optimal threshold of 27.9%. However, for relatively less deadly conditions such as prostate cancer, 2.5% is more risk-tolerant or aggressive than the BDA-optimal threshold of 1.2%. We compute BDA-optimal sizes for 25 of the most lethal diseases and show how a BDA-informed approval process can incorporate all stakeholders’ views in a systematic, transparent, internally consistent, and repeatable manner. https://www.nber.org/papers/w21499 https://www.nber.org/papers/w21499

Retric 7y ago

Only a fraction of drugs treat life threatening condition in some new way. Painkillers for example represent a surprising fraction of all drugs and generally have a close equivalent. https://www.drugs.com/condition/pain.html https://www.drugs.com/condition/pain.html Taking enough time to endure a new acne medication or Viagra alternative etc is reasonably safe is very much worth spending some extra time. Edit: This does seem to be focused on needed medications without close equivalents but that’s a fairly arbitrary line.

1123581321 7y ago
It is as long as the FDA can operate flexibly enough to not spend extra time where they shouldn’t. If they can’t, as seems to have been the case historically, then it’s best overall from a mortality and longevity perspective if they err on the side of faster releases. Note that faster operation also means they can more quickly act on feedback from the market and medical practitioners post release.
tpmoney 7y ago
Close equivalent can still be something you can't take. For example, if you're one of the unfortunate people with no activity on your CYP2D6 enzyme, there are essentially 4 pain medications that you can take at appropriate doses once you need something stronger than advil: Morphine, Dilaudid, Oxymorphone and Fentanyl, and there are reasons why doctors prefer other narcotics before prescribing any of those 4. Other pain medications will work, but you'll likely need inappropriately higher doses[0], which can lead to other problems (like overdosing). Likewise if you process faster than a normal person (i.e. you have more activity on that enzyme) you can overdose at normal prescribing doses. Close equivalents for some people can indeed be the difference between life and death, even if the condition itself isn't life threatening. [0]: https://www.ncbi.nlm.nih.gov/books/NBK100662/ https://www.ncbi.nlm.nih.gov/books/NBK100662/
- Retric 7y ago
  That’s a very good point, but then we are talking about edge cases and a delay measured in weeks to months. So, the benefit from catching 1 bad drug could outweigh the benefits from releasing 100 drugs slightly earlier. It’s not an easy choice, especially when the risks are often hypothetical and the benefits so clear. It’s interesting looking at lists like this and considering where things broken down. https://en.m.wikipedia.org/wiki/List_of_withdrawn_drugs https://en.m.wikipedia.org/wiki/List_of_withdrawn_drugs

StacyRoberts 7y ago

We need to allow people to self care so you can hack your own diabetes. I wish I could buy my own life sustaining hormone that I've been using for 20 years and understand better than most doctors outside endocrinology.

big_chungus 7y ago
I have a friend who has to regularly go to Europe to replace her implantable pump. It's not approved in America because the bureaucrats haven't gotten around to it. So long as there's no false advertising, let people try treatments that work for them, even if there's risk. Said friend has enough money that she's okay, but most others aren't so lucky.
- StacyRoberts 7y ago
  I dated someone with an external pump. It came off one day and caused so many problems. Just slid from sitting on the couch to the floor watching tv and the cushion caught the pump and broke it off. I immediately thought that type of failure should be recoverable without a hospital visit and surgery and tried to figure out why it wasn't. My mind immediately set to making it so and was held back by the fear I could go to prison for practicing medicine without a license. "I love you. I wish I could fix you. I could fix you." "I know you could. I wish you could."
  - ntdb 7y ago
    [T1D who used an external Medtronic pump for years here] Normally that kind of failure would be quickly recoverable without a hospital visit/surgery, I’m sorry that this one was not.
  - deleted 7y ago
    [deleted]
  - ng12 7y ago
    There are some other options. I use a pump (OmniPod) that is entirely attached to my body. There's a small plastic pod that's taped to the skin and operated wirelessly. My chief complaint is that the FDA is overly restrictive. They force manufacturers to make the products expire earlier to head off concerns about them working less efficiently near the end of the cycle. Diabetes is a disease who's treatment is entirely about guesstimating but the FDA does not take that into account when approving devices.