4 ms·

> Another example involves nerve growth factor inhibitors like tanezumab. Although tanezumab alleviated inflammatory pain from conditions like osteoarthritis, P

> Another example involves nerve growth factor inhibitors like tanezumab. Although tanezumab alleviated inflammatory pain from conditions like osteoarthritis, Phase III trials revealed an unfortunate side effect: rapidly progressive osteoarthritis. Researchers hypothesized that because patients felt so much better, they overused their arthritic joints, accelerating damage. Although further trials were conducted at lower doses and with restrictions, the FDA ultimately voted against its approval. Really not sure how to feel about this part lol, I mean I get it, but at the same time this is very ugh.

dakial1 1y ago
Well, pain exists for a reason for animals to pay attention to things that are harming the body. If you remove the flag (pain), harm will continue.
- perching_aix 1y ago
  Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening, which is the other "ugh" part to this. That said, the article may not be fairly representing what happened in the first place, so...
  - jjulius 1y ago
    >Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Clicking "FDA" in the bit you quoted above takes you to a different page wherein the FDA laments the lack of data around the drug (eg, the "hypothesized mechanism"). It also suggests that the companies intend to work with the FDA more on this. Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
    - perching_aix 1y ago
      > Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"? Why do you present this as an either/or? > Clicking "FDA" in the bit you quoted above takes you to a different page Indeed, where I found that... > That said, the article may not be fairly representing what happened in the first place, so... ...this is exactly what happened, i.e. I was successfully misled even before reaching your false dichotomy. Yay.
      - jjulius 1y ago
        >Why do you present this as an either/or? >... your false dichotomy. I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy. I didn't intend to present it as an "either/or", though I can see how it can be read that way. I simply read you saying that they "completely prevent[ed]" something from coming to market when, perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That the "incomplete justification" you lamented may also have been how the FDA felt about the data provided to them. It could also be for other reasons, absolutely! This is just one possibility that seems very obvious to me. There's no either/or from my end.
        perching_aix 1y ago
        > I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy. If I didn't already conclude that you presented a false dichotomy, why would I have inquired about why you did so? It's also not set in stone; from your reply I can just change my mind afterwards. But why do it in two rounds when I can do it in one? I understand if I came across as hostile though, I admit it was sadly reflexive, and I apologize. > perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That's not a nuance I intended to disregard. Yes, I understand they can revisit the drug's approval later, didn't mean to suggest otherwise. Gosh I hate natural language sometimes.
  - esperent 1y ago
    > Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening The more I learn about pharmacology, the more I realize this is the norm, rather than the exception.
- mrweasel 1y ago
  That's a very real concern. A friend of mine has a higher than normal threshold for pain and have permanent injuries as a result. Among other things has walked around on a broken foot for months and failed to register a back injury. All of this then escalated to the point where she feels the pain, but the injuries have become permanent.
  - Karawebnetwork 1y ago
    I have a similar condition. For me, the issue isn't so much the sensation of the permanent injuries themselves, but rather the constant physical fatigue that comes with them. Since doctors tend to rely heavily on those 1-to-10 pain scales with the little face expressions, it's incredibly hard to be taken seriously when your symptoms don't fit neatly into that system. What's frustrating is that people who can feel the pain early on often have a chance to prevent further damage. I couldn't and doctors couldn't even help me identify that I might have health issues. I worry a lot about aging, and I'm also afraid of things like tumors or cancers that I might not feel until it's too late. As an example, I can't feel cavities forming and I didn't even notice my wisdom teeth piercing through my gums when I was a teen.
  - atombender 1y ago
    A rheumatologist explained to me that in people with chronic pain from things like arthritis, the brain's pain perception can become permanently altered to register pain that no longer "exists". She explained that the brain itself is really the source of the sensation of pain, and you don't necessarily need a "real" source producing a signal. So one should at least not ignore pain if one can avoid it.
    - rpaddock 1y ago
      My late wife took her own life because of Chronic Pain. She was told "The pain has become fixed in your perception". Many years later we found that the actual cause was a Cerebrospinal Fluid (CSF) Leak. After two failed surgeries to fix it, she had enough and checked herself out. See our documentary Pain Warriors for the whole saga.
- IrishTechie 1y ago
  In that case maybe, but there are plenty of cases where pain is not indicating harm and may actually prevent people from reducing harm.
lr4444lr 1y ago
The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings. The agency bears zero responsibility for the pain and suffering its caused by overcaution.
- ta20240528 1y ago
  > The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings. Thalidomide. Patients (and often doctors) really don't have the skills or information to make an informed decision. They can however have 'feelings'. This is not the same thing.
  - eej71 1y ago
    I think your argument hinges on the implied idea that whoever makes up these entities (the FDA or otherwise) are intrinsically made of finer clay that the rest of us mere mortals.
    - ta20240528 1y ago
      For the avoidance of doubt, I'm not implying anything; I'm categorically stating it: experts are better than the hoi poloi. Always. To continue my example of thalidomide, the FDA's Dr. Frances Oldham Kelsey prevented millions of American babies from being born with devastating deformities. At the same time millions of American mothers and their GP's were clamoring for the anti-nausea drug that the British mother's were enjoying. And they too said the FDA was getting in their way. Experts aren't "made of finer clay" : they just know a lot more than the populace about specific topics. There are other topics where I am the finer clay. See 'specialisation'.
  - lr4444lr 1y ago
    "This isn't FDA approved, and could come with risks. I have not seen any in my patients, but it is a possibility" is informed consent.
DebtDeflation 1y ago
Meanwhile, good old aspirin is not only an effective pain reliever but it has also been shown to reverse the effect of cartilage loss in osteoarthritis: https://www.sciencedirect.com/science/article/abs/pii/S0378512215006684 https://www.sciencedirect.com/science/article/abs/pii/S03785... And that's not even taking into account its cardioprotective effects. But hey, it can be hard on the stomach in SOME people so we developed alternatives with all sorts of nasty side effects, up to and including heart attacks and strokes (rofecoxib, valdecoxib, etc.) Hell, a decade ago, the FDA issued an advisory across the board that "Non-aspirin NSAIDS increase the risk of heart attacks and strokes": https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory https://www.fda.gov/drugs/drug-safety-and-availability/fda-d... Some day we will look back on the attempted replacement of aspirin with these other drugs the same way we now look back on the replacement of butter with margarine (and the replacement of saturated fats with trans fats more broadly).
EasyMark 1y ago
maybe they could lower the dosage in future studies? I'm sure they've considered that though and will take it into account.

dakial1 1y ago

Well, pain exists for a reason for animals to pay attention to things that are harming the body. If you remove the flag (pain), harm will continue.

perching_aix 1y ago
Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening, which is the other "ugh" part to this. That said, the article may not be fairly representing what happened in the first place, so...
- jjulius 1y ago
  >Sure, it just feels like an incomplete justification to completely prevent a drug from entering the market and being used. Clicking "FDA" in the bit you quoted above takes you to a different page wherein the FDA laments the lack of data around the drug (eg, the "hypothesized mechanism"). It also suggests that the companies intend to work with the FDA more on this. Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"?
  - perching_aix 1y ago
    > Was the vote against approval a move to "completely prevent a drug from entering the market and being used", or was it a desire to better understand it before saying "okay"? Why do you present this as an either/or? > Clicking "FDA" in the bit you quoted above takes you to a different page Indeed, where I found that... > That said, the article may not be fairly representing what happened in the first place, so... ...this is exactly what happened, i.e. I was successfully misled even before reaching your false dichotomy. Yay.
    - jjulius 1y ago
      >Why do you present this as an either/or? >... your false dichotomy. I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy. I didn't intend to present it as an "either/or", though I can see how it can be read that way. I simply read you saying that they "completely prevent[ed]" something from coming to market when, perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That the "incomplete justification" you lamented may also have been how the FDA felt about the data provided to them. It could also be for other reasons, absolutely! This is just one possibility that seems very obvious to me. There's no either/or from my end.
      - perching_aix 1y ago
        > I appreciate you giving me the opportunity to answer your first question before coming to the conclusion that I was using a false dichotomy. If I didn't already conclude that you presented a false dichotomy, why would I have inquired about why you did so? It's also not set in stone; from your reply I can just change my mind afterwards. But why do it in two rounds when I can do it in one? I understand if I came across as hostile though, I admit it was sadly reflexive, and I apologize. > perhaps, they're not "completely" doing anything and are open to doing it provided that they know more about it. That's not a nuance I intended to disregard. Yes, I understand they can revisit the drug's approval later, didn't mean to suggest otherwise. Gosh I hate natural language sometimes.
- esperent 1y ago
  > Also, that was just the hypothesized mechanism at play, it may not have been what was actually happening The more I learn about pharmacology, the more I realize this is the norm, rather than the exception.
mrweasel 1y ago
That's a very real concern. A friend of mine has a higher than normal threshold for pain and have permanent injuries as a result. Among other things has walked around on a broken foot for months and failed to register a back injury. All of this then escalated to the point where she feels the pain, but the injuries have become permanent.
- Karawebnetwork 1y ago
  I have a similar condition. For me, the issue isn't so much the sensation of the permanent injuries themselves, but rather the constant physical fatigue that comes with them. Since doctors tend to rely heavily on those 1-to-10 pain scales with the little face expressions, it's incredibly hard to be taken seriously when your symptoms don't fit neatly into that system. What's frustrating is that people who can feel the pain early on often have a chance to prevent further damage. I couldn't and doctors couldn't even help me identify that I might have health issues. I worry a lot about aging, and I'm also afraid of things like tumors or cancers that I might not feel until it's too late. As an example, I can't feel cavities forming and I didn't even notice my wisdom teeth piercing through my gums when I was a teen.
- atombender 1y ago
  A rheumatologist explained to me that in people with chronic pain from things like arthritis, the brain's pain perception can become permanently altered to register pain that no longer "exists". She explained that the brain itself is really the source of the sensation of pain, and you don't necessarily need a "real" source producing a signal. So one should at least not ignore pain if one can avoid it.
  - rpaddock 1y ago
    My late wife took her own life because of Chronic Pain. She was told "The pain has become fixed in your perception". Many years later we found that the actual cause was a Cerebrospinal Fluid (CSF) Leak. After two failed surgeries to fix it, she had enough and checked herself out. See our documentary Pain Warriors for the whole saga.
IrishTechie 1y ago
In that case maybe, but there are plenty of cases where pain is not indicating harm and may actually prevent people from reducing harm.

lr4444lr 1y ago

The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings. The agency bears zero responsibility for the pain and suffering its caused by overcaution.

ta20240528 1y ago
> The FDA interfering with informed consent between doctor and patient isn't something I find a source of complex feelings. Thalidomide. Patients (and often doctors) really don't have the skills or information to make an informed decision. They can however have 'feelings'. This is not the same thing.
- eej71 1y ago
  I think your argument hinges on the implied idea that whoever makes up these entities (the FDA or otherwise) are intrinsically made of finer clay that the rest of us mere mortals.
  - ta20240528 1y ago
    For the avoidance of doubt, I'm not implying anything; I'm categorically stating it: experts are better than the hoi poloi. Always. To continue my example of thalidomide, the FDA's Dr. Frances Oldham Kelsey prevented millions of American babies from being born with devastating deformities. At the same time millions of American mothers and their GP's were clamoring for the anti-nausea drug that the British mother's were enjoying. And they too said the FDA was getting in their way. Experts aren't "made of finer clay" : they just know a lot more than the populace about specific topics. There are other topics where I am the finer clay. See 'specialisation'.
- lr4444lr 1y ago
  "This isn't FDA approved, and could come with risks. I have not seen any in my patients, but it is a possibility" is informed consent.

DebtDeflation 1y ago

Meanwhile, good old aspirin is not only an effective pain reliever but it has also been shown to reverse the effect of cartilage loss in osteoarthritis: https://www.sciencedirect.com/science/article/abs/pii/S0378512215006684 https://www.sciencedirect.com/science/article/abs/pii/S03785... And that's not even taking into account its cardioprotective effects. But hey, it can be hard on the stomach in SOME people so we developed alternatives with all sorts of nasty side effects, up to and including heart attacks and strokes (rofecoxib, valdecoxib, etc.) Hell, a decade ago, the FDA issued an advisory across the board that "Non-aspirin NSAIDS increase the risk of heart attacks and strokes": https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory https://www.fda.gov/drugs/drug-safety-and-availability/fda-d... Some day we will look back on the attempted replacement of aspirin with these other drugs the same way we now look back on the replacement of butter with margarine (and the replacement of saturated fats with trans fats more broadly).

EasyMark 1y ago

maybe they could lower the dosage in future studies? I'm sure they've considered that though and will take it into account.