>This is contradictory. Most drugs fail, how do we identify the efficacious ones other than through trials?
One idea is to make trials somewhat less costly by relying more on post-approval monitoring, but there are more subtle critiques of the processes that try to address perceived inefficiencies at the organisation/bureaucratic level rather than just adjusting a single big strict/lenient dial.
Some drugs do not make it to trial at all due to the overwhelming cost of the process. We would identify a larger number of efficacious ones if there were less costly, wider trials. A very expensive approval process results in delays for drugs that do make it to trials, but also causes many candidates to never reach trials.
>Depending on the anticipated efficacy from early trials as compared to existing ones it will get fast-tracked before the phase II is completed.
Part of the argument is that this is good, and we should consider going further in that direction
>Where is the evidence that we’re delaying efficacious therapies where there is no good alternative?
Unfortunately, the best I can point to is a series of blog posts and informal discussions, I'm not aware of any formal published evidence. I remember a blog post on ACX post aducanumab (https://astralcodexten.substack.com/p/adumbrations-of-aducan...). The "FDA delenda est" catchprase leads to several more posts.
I'll admit this is not very compelling. I believe it's worth having that argument, and I'd be happy to be wrong on that one, but all of this is hard to quantify.
(I also want to reaffirm that there are good alternatives, it's a question of whether we could be losing less people than we are losing under the current process, not that there are no current alternatives)
>I sound like a broken record right now but this blog post is suggesting we jump to experimental therapies (which would be off label for the author as he does not meet inclusion criteria) before we even have phase I data let alone efficacy, when good validated treatment options exists.
I'm sorry if I'm repeating myself as well or failing to make a good argument. I think your position is very reasonable. It's a complicated topic and I might not be doing it justice.
> Unfortunately, the best I can point to is a series of blog posts and informal discussions, I'm not aware of any formal published evidence. I remember a blog post on ACX post aducanumab (https://astralcodexten.substack.com/p/adumbrations-of-aducan...). The "FDA delenda est" catchprase leads to several more posts.
I'm a radiologist by training with an interventional oncology component in my practice so I can really only speak to acute care emergencies and cancer with any degree of expertise.
Cancer, heart attacks, strokes, aneurysms are different because there's a time crunch. In these situations FDA approval comes quickly for new medical devices and imaging tests. New aneurysms occlusion devices, stent grafts, and thrombectomy devices are all quickly approved with shortened review processes. Sometimes this has been to our detriment (e.g. early abdominal aortic/EVAR grafts which all leaked and caused disasters when the patient needed re-operation).
In these cases we did exactly what you're suggesting with:
> One idea is to make trials somewhat less costly by relying more on post-approval monitoring
How this translates to other diseases like Alzheimer's is not in my wheelhouse. I assume the process is more strictly adhered to in these cases, but it presumably should be because the potential harm of delaying is seemingly less important unless we're discussing disease-modifying treatments that require early initiation.
In your post the author mentions COVID-19 vaccinations, these were made available before full FDA approval. COVID-19 was highly politicized and the entire process did not follow typical medical procedures. Honestly the evidence that has come out for them isn't very compelling (omicron and later) and largely why most places have dropped vaccination requirements. I'm not sure that this is a good example of the "FDA's failure".
One idea is to make trials somewhat less costly by relying more on post-approval monitoring, but there are more subtle critiques of the processes that try to address perceived inefficiencies at the organisation/bureaucratic level rather than just adjusting a single big strict/lenient dial.
Some drugs do not make it to trial at all due to the overwhelming cost of the process. We would identify a larger number of efficacious ones if there were less costly, wider trials. A very expensive approval process results in delays for drugs that do make it to trials, but also causes many candidates to never reach trials.
>Depending on the anticipated efficacy from early trials as compared to existing ones it will get fast-tracked before the phase II is completed.
Part of the argument is that this is good, and we should consider going further in that direction
>Where is the evidence that we’re delaying efficacious therapies where there is no good alternative?
Unfortunately, the best I can point to is a series of blog posts and informal discussions, I'm not aware of any formal published evidence. I remember a blog post on ACX post aducanumab (https://astralcodexten.substack.com/p/adumbrations-of-aducan...). The "FDA delenda est" catchprase leads to several more posts.
I'll admit this is not very compelling. I believe it's worth having that argument, and I'd be happy to be wrong on that one, but all of this is hard to quantify.
(I also want to reaffirm that there are good alternatives, it's a question of whether we could be losing less people than we are losing under the current process, not that there are no current alternatives)
>I sound like a broken record right now but this blog post is suggesting we jump to experimental therapies (which would be off label for the author as he does not meet inclusion criteria) before we even have phase I data let alone efficacy, when good validated treatment options exists.
I'm sorry if I'm repeating myself as well or failing to make a good argument. I think your position is very reasonable. It's a complicated topic and I might not be doing it justice.