3 ms·

Thank you, Jake! ---and your family--- for your links and work that highlight the importance of clinical trials for mRNA tumor vaccines! Will keep posting to HN

Thank you, Jake! ---and your family--- for your links and work that highlight the importance of clinical trials for mRNA tumor vaccines! Will keep posting to HN her articles when they come out. https://archive.ph/bessstillman.substack.com https://archive.ph/bessstillman.substack.com (Archive listing jseliger's wife Bess Stillman on clinical trials (including how to navigate them as patients) as well as comments) Suggestions for concrete directions that have been mentioned, that are worth highlighting, in order of importance: 0) assume good faith 1) promote (& improve) Right-to-Try https://www.fda.gov/media/133864/download#:~:text=Right%20to https://www.fda.gov/media/133864/download#:~:text=Right%20to.... 2) donate to (or even joining!) HN-adjacent Arc Institute (mRNA translational research) 3) sue the FDA for clinical trials, in general. This is not a call to attack on the FDA, but perhaps the best way, to improve processes, that is available to citizens. Here's one case https://www.theatlantic.com/health/archive/2023/10/xocova-en https://www.theatlantic.com/health/archive/2023/10/xocova-en...

A_D_E_P_T 2y ago
> This is not a call to attack on the FDA At this point, I honestly think that we'd be much better off without an FDA at all. It costs >$2B to develop a drug. Most of this is on account of efficacy testing -- phases 2 and 3 of the drug development process -- which are nearly impossible to run. And when drugs exhibit poor or nil efficacy, the FDA sometimes approves them anyway, making the entire process unprincipled. See, e.g., flibanserin, aduhelm, and others. The result is total regulatory capture. If you're a small firm -- a biotech startup -- you quite literally can't introduce a new drug to the market. Your only hope is to push it through preclinical trials and then partner with -- or get bought out by -- a large "prime" like Pfizer which specializes in regulatory compliance and has the deep pockets required. Back in the 1940s and 1950s, there were lots of small firms that competed in drug development. Syntex, for instance. That was a period the industry still calls "The Golden Age of Drug Development," and it would be utterly impossible to recreate today. All of this is without even going into the bureaucratic hurdles which delay new treatments from reaching patients, the chilling effect that the red tape has on pharmaceutical R&D, the way they gatekeep generics, and I could go on all day. It's not just a bad system, it might be among the worst systems possible, as it concentrates all power and all wealth in the hands of a few -- and the patients are the ones who suffer for it.
- vinnyvichy 2y ago
  I hear you..
- Palomides 2y ago
  it's very bureaucratic, but I'm curious what phases of the process you think we can skip? was the golden age entirely due to lack of procedural burden, or just low hanging fruit? I agree that it's all a miserable mess, for sure, the solutions are just unclear to me; the relationship between the public and those developing drugs is increasingly hostile due to the need for blockbuster hits and really questionable effect sizes that get pushed due to sunk costs
  - A_D_E_P_T 2y ago
    Efficacy testing -- those phases 2 and 3 -- are entirely unnecessary. They didn't exist prior to 1962's Thalidomide backlash, ironically despite the fact that Thalidomide failed safety testing in the US and was not approved for use. So it's simple: After phase 1 safety testing, allow drugs to be marketed, but mandate postmarketing surveillance for a period of 5 years to try and tease out real-world safety, efficacy, and drug interactions. This would ultimately result in a better and safer system, as quite a lot of drugs have problems that aren't revealed in phases 2/3 anyway. (e.g. rosiglitazone.) This simple fix would not only speed up drug development, it would also make drug development a lot cheaper. Compared to the current paradigm, it would heavily incentivize R&D, and bright young minds might see the development of therapeutics as something potentially rewarding. Whereas, today, nobody in their right mind wants to get into pharmaceutical development when they could be making much more money, with much less red tape, in tech.
    - Palomides 2y ago
      how would someone under such a system decide to take a drug or not? what information would they have?
      - JackFr 2y ago
deleted 2y ago
[deleted]
vinnyvichy 2y ago
Sorry to be presumptuous, dang, but lifes are at stake.. I'll take responsibility until we all have time to think about forum mechanism redesign I know it's a tough job, I have thought about applying myself..
- vinnyvichy 2y ago
  I wish to delete this above comment , but I cannot. I am sorry!
  - dredmorbius 2y ago
    Email such requests to the mods at hn@ycombinator.com. Include the URLs or item IDs of the items you wish addressed or deleted. The above comment is ID 41170978. Putting that in the subject or body of your email greatly facilitates mod actions. (Mods doing cleanup: you're welcome to delete this comment as well when addressing this thread.)
deleted 2y ago
[deleted]

A_D_E_P_T 2y ago

> This is not a call to attack on the FDA At this point, I honestly think that we'd be much better off without an FDA at all. It costs >$2B to develop a drug. Most of this is on account of efficacy testing -- phases 2 and 3 of the drug development process -- which are nearly impossible to run. And when drugs exhibit poor or nil efficacy, the FDA sometimes approves them anyway, making the entire process unprincipled. See, e.g., flibanserin, aduhelm, and others. The result is total regulatory capture. If you're a small firm -- a biotech startup -- you quite literally can't introduce a new drug to the market. Your only hope is to push it through preclinical trials and then partner with -- or get bought out by -- a large "prime" like Pfizer which specializes in regulatory compliance and has the deep pockets required. Back in the 1940s and 1950s, there were lots of small firms that competed in drug development. Syntex, for instance. That was a period the industry still calls "The Golden Age of Drug Development," and it would be utterly impossible to recreate today. All of this is without even going into the bureaucratic hurdles which delay new treatments from reaching patients, the chilling effect that the red tape has on pharmaceutical R&D, the way they gatekeep generics, and I could go on all day. It's not just a bad system, it might be among the worst systems possible, as it concentrates all power and all wealth in the hands of a few -- and the patients are the ones who suffer for it.

vinnyvichy 2y ago
I hear you..
Palomides 2y ago
it's very bureaucratic, but I'm curious what phases of the process you think we can skip? was the golden age entirely due to lack of procedural burden, or just low hanging fruit? I agree that it's all a miserable mess, for sure, the solutions are just unclear to me; the relationship between the public and those developing drugs is increasingly hostile due to the need for blockbuster hits and really questionable effect sizes that get pushed due to sunk costs
- A_D_E_P_T 2y ago
  Efficacy testing -- those phases 2 and 3 -- are entirely unnecessary. They didn't exist prior to 1962's Thalidomide backlash, ironically despite the fact that Thalidomide failed safety testing in the US and was not approved for use. So it's simple: After phase 1 safety testing, allow drugs to be marketed, but mandate postmarketing surveillance for a period of 5 years to try and tease out real-world safety, efficacy, and drug interactions. This would ultimately result in a better and safer system, as quite a lot of drugs have problems that aren't revealed in phases 2/3 anyway. (e.g. rosiglitazone.) This simple fix would not only speed up drug development, it would also make drug development a lot cheaper. Compared to the current paradigm, it would heavily incentivize R&D, and bright young minds might see the development of therapeutics as something potentially rewarding. Whereas, today, nobody in their right mind wants to get into pharmaceutical development when they could be making much more money, with much less red tape, in tech.
  - Palomides 2y ago
    how would someone under such a system decide to take a drug or not? what information would they have?
    - JackFr 2y ago

deleted 2y ago

[deleted]

vinnyvichy 2y ago

Sorry to be presumptuous, dang, but lifes are at stake.. I'll take responsibility until we all have time to think about forum mechanism redesign I know it's a tough job, I have thought about applying myself..

vinnyvichy 2y ago
I wish to delete this above comment , but I cannot. I am sorry!
- dredmorbius 2y ago
  Email such requests to the mods at hn@ycombinator.com. Include the URLs or item IDs of the items you wish addressed or deleted. The above comment is ID 41170978. Putting that in the subject or body of your email greatly facilitates mod actions. (Mods doing cleanup: you're welcome to delete this comment as well when addressing this thread.)

deleted 2y ago

[deleted]