5 ms·

>These unjustified exclusions can have real clinical implications, too. For example, most asthma studies exclude morbidly obese people, as morbidly obese asthma

>These unjustified exclusions can have real clinical implications, too. For example, most asthma studies exclude morbidly obese people, as morbidly obese asthma is notoriously resistant to treatment and there aren’t good explanations as to why. However, once asthma drugs are approved, they’re approved for all asthmatics equally. As a result, morbidly obese people get prescribed asthma drugs that were never tested on people like them [1]. >[...] >[1] This is literally going on today by the way. The FDA approved Tezpire as a breakthrough drug for asthma in December 2021. Tezspire excluded morbidly obese people from their efficacy trials. This fact is not mentioned anywhere in Tezspire’s labeling. Wow, I had never heard of anything like this before. Does the FDA have a justification for why there isn't a requirement to mention significant exclusions like this?

photochemsyn 5y ago
I believe the FDA relies on the "maximum expected utility principle" - a cornerstone of free-market economic theory. > "By combining the concept of utility with the notion of rational decision making, economists in the mid-twentieth century established a basis for the maximum expected utility principle. This principle is a key concept behind the creation of autonomous decision-making agents." https://algorithmsbook.com/files/dm.pdf https://algorithmsbook.com/files/dm.pdf This has been expressed in the past as "Each portion of wealth has a corresponding portion of happiness, and of two individuals with unequal fortunes, he who has the most wealth has the most happiness." A good way to accumulate wealth and maximize happiness is to sell drugs, and preventing the sale of drugs because of concerns over ill effects reduces wealth and brings sadness to the pharmaceutical corporation and its shareholders and board members; such sadness prevents them from hiring ex-FDA employees as consultants or managers, thus defeating the principle of maximum expected utility. The autonomous decision-making agents at the FDA therefore have no choice but to rubber stamp everything that comes across their desk. Doing anything else would be irrational.
- toto444 5y ago
  > I believe the FDA relies on the "maximum expected utility principle" - a cornerstone of free-market economic theory. This has nothing to do with 'free-market economic theory'. It's about decision under uncertainty. The concept was expressed for the first time by Von Neumann and Morgenstern in a book that was supposed to explain how to play poker. > "Each portion of wealth has a corresponding portion of happiness, and of two individuals with unequal fortunes, he who has the most wealth has the most happiness." I have never ever read that anywhere. One could argue that rich people provide more value to society and then should be prioritise in some circumstances but what you are writing seems very unfounded.
  - photochemsyn 5y ago
    You can get that quote from the linked text. Notice I'm not actually attacking 'free-market economic theory' per se - but we could adjust the behavior of FDA regulators and pharmaceutical corporate boards by (1) banning FDA regulators from ever taking jobs or gifts from the entities they're supposed to be regulating and (2) enforcing criminal penalties for fraud and deception in the pharmaceutical sector. There's nothing like a 5-10 year term in an American prison to reduce happiness...
    - toto444 5y ago
      > You can get that quote from the linked text True. Utility is increasing with revenue. I misunderstood this part of your comment. I read it as : 'if we want to maximum social utility let's prioritise rich people'.
  - samhw 5y ago
    > I have never ever read that anywhere. One could argue that rich people provide more value to society and then should be prioritise in some circumstances but what you are writing seems very unfounded. Nor have I. It's such a remarkably stupid statement that it strikes me as stupid in itself to think anyone should be so stupid as to believe it. It's also nothing whatsoever to do with expected utility theory (I don't know where they did get it from). 'Utility monsters' - per Rawls - are a valid objection; 'money monsters' are not, for the very reason that marginal economic gain is not equivalent to marginal gain in happiness/utility, nor would anyone think it is.
- gumby 5y ago
  > The autonomous decision-making agents at the FDA therefore have no choice but to rubber stamp everything that comes across their desk. Doing anything else would be irrational. You have clearly never tried to get a drug or device approved nor have you looked at the number of drugs that fail, expensively, in Phase 2 or even Phase 3. Your statement is utter nonsense.
gumby 5y ago
As someone who has both designed and run clinical trials as my job, this assertion is likely* nonsense. First, the division you submit to will reject your recruitment criteria if they feel it does not accurately reflect the treatment population within the United States. They also reflect the specialty of the particular division (e.g. Oncology is allegedly far less worried about most side effects than, say, the Dermatology division, due to the kinds of indications they deal with). Second of all this kind of info is on the label (prescribing information) even if it doesn’t make it into the short summary (package insert, typically only a dozen pages or so) given to patients. Doctors do read those, you know, and within their specialities know what kinds of things to look for. There have been some notorious cases, but by and large I’ve found the people I worked with at the agency to be professional and solid. I’m no longer in that business and have no reason to say anything I don’t believe. * I didn’t bother to look up the label for this drug but they are all public info on the FDA web site and In the USP.
- lkey 5y ago
  Why on Earth did you not bother to look it up before asserting your opinion...? https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761224s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/76... Body Weight Based on population pharmacokinetic analysis, higher body weight was associated with lower exposure. However, the effect of body weight on exposure had no meaningful impact on efficacy or safety and does not require dose adjustment. Assuming that grandparent comment is correct about morbid obesity exclusion, then you were the one spouting nonsense right? Doctors will definitely give this to patients regardless of weight with a note like that.
  - gumby 5y ago
    Both my note and the download you discuss are clear about this. You have linked to the the package insert, not the label, and it clearly states at the very top HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use TEZSPIRE safely and effectively. See full prescribing information for TEZSPIRE. As I wrote in my comment: > ... this kind of info is on the label (prescribing information) even if it doesn’t make it into the short summary (package insert, typically only a dozen pages or so) given to patients. Doctors do read those, you know, and within their specialities know what kinds of things to look for. You are simply quoting the short summary and drawing a conclusion based on the limited information that appears on it. Perhaps the author of the blog post made the same error. The doctor reads the actual prescribing information and the evaluation population must be specified there.
chmod775 5y ago
I feel like I have to play devil's advocate here a bit. Obesity is an easily treatable condition. One might try to treat them in order: Obesity first, then the asthma. That would justify excluding that particular complication from the study.
- AlchemistCamp 5y ago
  > Obesity is an easily treatable condition. Is it? I thought long-term success rates were very low and that prevalence was increasing all over the globe.
  - bryan_w 5y ago
    Also a person who has trouble breathing tends to not do significant exercise because they run out of breath too quickly.
    - jallen_dot_dev 5y ago
      While exercise is healthy, it isn't a great way to lose weight. Eating a healthier diet, in particular lower calorie, is how you lose weight.
  - chmod775 5y ago
    prevalence != difficulty of treatment people's unwillingness to cooperate != difficulty of treatment Asthma also isn't the only condition that is hard to treat in morbidly obese people. For many conditions it will be too late to start paying attention to one's calorie intake, but asthma is one that is survivable in the meantime. Severe discomfort and possible death tends to be a good motivator.
    - throwthere 5y ago
      Researchers generally analyze intervention success by intention to treat. If a treatment is telling people to "start paying attention to one's calorie intake," and that doesn't have the desired effect, whatever the reason, I think it's fair to say that intervention isn't useful.
refresherd 5y ago
Much like sleep apnea in the morbidly obese, this is likely just a different condition entirely with a physical cause. As to why it is prescribed anyways - like the MD who taught me about sleep apnea said, morbidly obese people get offended when you suggest that there aren't drugs that you can give them and they just need to take some extra weight off the strained organs. It's easier to give a person who is certain that it's not the weight, but some condition solvable with drugs, a drug.

photochemsyn 5y ago

I believe the FDA relies on the "maximum expected utility principle" - a cornerstone of free-market economic theory. > "By combining the concept of utility with the notion of rational decision making, economists in the mid-twentieth century established a basis for the maximum expected utility principle. This principle is a key concept behind the creation of autonomous decision-making agents." https://algorithmsbook.com/files/dm.pdf https://algorithmsbook.com/files/dm.pdf This has been expressed in the past as "Each portion of wealth has a corresponding portion of happiness, and of two individuals with unequal fortunes, he who has the most wealth has the most happiness." A good way to accumulate wealth and maximize happiness is to sell drugs, and preventing the sale of drugs because of concerns over ill effects reduces wealth and brings sadness to the pharmaceutical corporation and its shareholders and board members; such sadness prevents them from hiring ex-FDA employees as consultants or managers, thus defeating the principle of maximum expected utility. The autonomous decision-making agents at the FDA therefore have no choice but to rubber stamp everything that comes across their desk. Doing anything else would be irrational.

toto444 5y ago
> I believe the FDA relies on the "maximum expected utility principle" - a cornerstone of free-market economic theory. This has nothing to do with 'free-market economic theory'. It's about decision under uncertainty. The concept was expressed for the first time by Von Neumann and Morgenstern in a book that was supposed to explain how to play poker. > "Each portion of wealth has a corresponding portion of happiness, and of two individuals with unequal fortunes, he who has the most wealth has the most happiness." I have never ever read that anywhere. One could argue that rich people provide more value to society and then should be prioritise in some circumstances but what you are writing seems very unfounded.
- photochemsyn 5y ago
  You can get that quote from the linked text. Notice I'm not actually attacking 'free-market economic theory' per se - but we could adjust the behavior of FDA regulators and pharmaceutical corporate boards by (1) banning FDA regulators from ever taking jobs or gifts from the entities they're supposed to be regulating and (2) enforcing criminal penalties for fraud and deception in the pharmaceutical sector. There's nothing like a 5-10 year term in an American prison to reduce happiness...
  - toto444 5y ago
    > You can get that quote from the linked text True. Utility is increasing with revenue. I misunderstood this part of your comment. I read it as : 'if we want to maximum social utility let's prioritise rich people'.
- samhw 5y ago
  > I have never ever read that anywhere. One could argue that rich people provide more value to society and then should be prioritise in some circumstances but what you are writing seems very unfounded. Nor have I. It's such a remarkably stupid statement that it strikes me as stupid in itself to think anyone should be so stupid as to believe it. It's also nothing whatsoever to do with expected utility theory (I don't know where they did get it from). 'Utility monsters' - per Rawls - are a valid objection; 'money monsters' are not, for the very reason that marginal economic gain is not equivalent to marginal gain in happiness/utility, nor would anyone think it is.
gumby 5y ago
> The autonomous decision-making agents at the FDA therefore have no choice but to rubber stamp everything that comes across their desk. Doing anything else would be irrational. You have clearly never tried to get a drug or device approved nor have you looked at the number of drugs that fail, expensively, in Phase 2 or even Phase 3. Your statement is utter nonsense.

gumby 5y ago

As someone who has both designed and run clinical trials as my job, this assertion is likely* nonsense. First, the division you submit to will reject your recruitment criteria if they feel it does not accurately reflect the treatment population within the United States. They also reflect the specialty of the particular division (e.g. Oncology is allegedly far less worried about most side effects than, say, the Dermatology division, due to the kinds of indications they deal with). Second of all this kind of info is on the label (prescribing information) even if it doesn’t make it into the short summary (package insert, typically only a dozen pages or so) given to patients. Doctors do read those, you know, and within their specialities know what kinds of things to look for. There have been some notorious cases, but by and large I’ve found the people I worked with at the agency to be professional and solid. I’m no longer in that business and have no reason to say anything I don’t believe. * I didn’t bother to look up the label for this drug but they are all public info on the FDA web site and In the USP.

lkey 5y ago
Why on Earth did you not bother to look it up before asserting your opinion...? https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761224s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/76... Body Weight Based on population pharmacokinetic analysis, higher body weight was associated with lower exposure. However, the effect of body weight on exposure had no meaningful impact on efficacy or safety and does not require dose adjustment. Assuming that grandparent comment is correct about morbid obesity exclusion, then you were the one spouting nonsense right? Doctors will definitely give this to patients regardless of weight with a note like that.
- gumby 5y ago
  Both my note and the download you discuss are clear about this. You have linked to the the package insert, not the label, and it clearly states at the very top HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use TEZSPIRE safely and effectively. See full prescribing information for TEZSPIRE. As I wrote in my comment: > ... this kind of info is on the label (prescribing information) even if it doesn’t make it into the short summary (package insert, typically only a dozen pages or so) given to patients. Doctors do read those, you know, and within their specialities know what kinds of things to look for. You are simply quoting the short summary and drawing a conclusion based on the limited information that appears on it. Perhaps the author of the blog post made the same error. The doctor reads the actual prescribing information and the evaluation population must be specified there.

chmod775 5y ago

I feel like I have to play devil's advocate here a bit. Obesity is an easily treatable condition. One might try to treat them in order: Obesity first, then the asthma. That would justify excluding that particular complication from the study.

AlchemistCamp 5y ago
> Obesity is an easily treatable condition. Is it? I thought long-term success rates were very low and that prevalence was increasing all over the globe.
- bryan_w 5y ago
  Also a person who has trouble breathing tends to not do significant exercise because they run out of breath too quickly.
  - jallen_dot_dev 5y ago
    While exercise is healthy, it isn't a great way to lose weight. Eating a healthier diet, in particular lower calorie, is how you lose weight.
- chmod775 5y ago
  prevalence != difficulty of treatment people's unwillingness to cooperate != difficulty of treatment Asthma also isn't the only condition that is hard to treat in morbidly obese people. For many conditions it will be too late to start paying attention to one's calorie intake, but asthma is one that is survivable in the meantime. Severe discomfort and possible death tends to be a good motivator.
  - throwthere 5y ago
    Researchers generally analyze intervention success by intention to treat. If a treatment is telling people to "start paying attention to one's calorie intake," and that doesn't have the desired effect, whatever the reason, I think it's fair to say that intervention isn't useful.

refresherd 5y ago

Much like sleep apnea in the morbidly obese, this is likely just a different condition entirely with a physical cause. As to why it is prescribed anyways - like the MD who taught me about sleep apnea said, morbidly obese people get offended when you suggest that there aren't drugs that you can give them and they just need to take some extra weight off the strained organs. It's easier to give a person who is certain that it's not the weight, but some condition solvable with drugs, a drug.