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To improve medical trials, justify exclusion criteria

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Re: To improve medical trials, justify exclusion criteria

#11

Post by pdonis »

photochemsyn wrote: post #4

Based on the record of the pharmaceutical industry and their entirely captured regulatory agency, the FDA, it's not entirely unwise to wait about ten years after the introduction of a 'breakthrough drug' to see if it actually has negative side effects that were not discovered in the clinical trials. See Vioxx, etc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC534432/ > "Dr Graham, associate director in the FDA's Offi…

> relatively safe and effective medicines (i.e. Sars-CoV2 vaccines)

By your own logic, we don't know this, because these vaccines haven't been in use long enough.

Re: To improve medical trials, justify exclusion criteria

#12

Post by lkey »

gumby wrote: post #8
meowface wrote: post #2

>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…

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 Dermat…

Why on Earth did you not bother to look it up before asserting your opinion...?

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.

Re: To improve medical trials, justify exclusion criteria

#13

Post by hallway_monitor »

pdonis wrote: post #11
photochemsyn wrote: post #4

Based on the record of the pharmaceutical industry and their entirely captured regulatory agency, the FDA, it's not entirely unwise to wait about ten years after the introduction of a 'breakthrough drug' to see if it actually has negative side effects that were not discovered in the clinical trials. See Vioxx, etc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC534432/ > "Dr Graham, associate director in the FDA's Offi…

> relatively safe and effective medicines (i.e. Sars-CoV2 vaccines) By your own logic, we don't know this, because these vaccines haven't been in use long enough.

Exactly this. In this case it does seem like emergency speed was justified. However, every year over 1,500 drugs are pulled off the shelves because, like vioxx, they were discovered later to have terrible side effects. Maybe some of these would have been found with different study demographics. Maybe not. Drugs are dangerous.

Re: To improve medical trials, justify exclusion criteria

#14

Post by photochemsyn »

toto444 wrote: post #7
photochemsyn wrote: post #6

Earlier quoted context omitted.

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.c…

> 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, a…

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...

Re: To improve medical trials, justify exclusion criteria

#15

Post by jahewson »

gumby wrote: post #8
meowface wrote: post #2

>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…

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 Dermat…

Oh the irony that you’ve excluded an investigation of the relevant example here, but made broad claims nonetheless.

Re: To improve medical trials, justify exclusion criteria

#16

Post by photochemsyn »

pdonis wrote: post #11
photochemsyn wrote: post #4

Based on the record of the pharmaceutical industry and their entirely captured regulatory agency, the FDA, it's not entirely unwise to wait about ten years after the introduction of a 'breakthrough drug' to see if it actually has negative side effects that were not discovered in the clinical trials. See Vioxx, etc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC534432/ > "Dr Graham, associate director in the FDA's Offi…

> relatively safe and effective medicines (i.e. Sars-CoV2 vaccines) By your own logic, we don't know this, because these vaccines haven't been in use long enough.

I personally went and got vaccinated the second month the Pfizer vaccine was released (but not the first) and even so I viewed myself more as a guinea pig in a clinical trial than anything else. As I had no immediate negative symptoms, I then got the second dose on schedule. Had some minor muscle stiffness in the arm after that one that persisted for a few months. I then got the booster when it came out, as at that point the data seemed pretty clear: side effects were minimal, and the risks of hospitalization and long Covid justified vaccination.

Notably however I certainly didn't expect that the vaccine wouldn't be 'sterilizing' and at the time the FDA was keeping quiet about the fact that vaccinated people could be asymptomatic carriers and spreaders of Sars-CoV2, which now seems widely accepted. The clinical data from the original trials has yet to be released as I understood it, and it likely showed that as well.

Re: To improve medical trials, justify exclusion criteria

#17

Post by toto444 »

photochemsyn wrote: post #14
toto444 wrote: post #7

Earlier quoted context omitted.

> 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, a…

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 not…

> 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'.

Re: To improve medical trials, justify exclusion criteria

#18

Post by ada1981 »

gumby wrote: post #8
meowface wrote: post #2

>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…

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 Dermat…

While you may not have financial incentives, the psychological incentives are often very strong to maintain a positive idea of an industry one was a part of.

Re: To improve medical trials, justify exclusion criteria

#19

Post by halyax »

duxup wrote: post #10

>There might well be good reasons for these exclusions that I’m not aware of. Is it possible that these reasons are more obvious or known to some folks and they just didn't list them, or they just wanted to see what happens without those groups, and it's not about shenanigans?

I do think there's a reasonably compelling case that drug companies could make for wanting to measure/demonstrate their drug's performance in an ideal population first - now the fact that they then go on to market the product with little to no care for the populations excluded from the trials undercuts this significantly. But it is at least possible that its not entirely shenanigans...
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