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I am dying of squamous cell carcinoma, and potential treatments are out of reach

jakeseliger.com

321–330 of 486 posts

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#321
post #304

Earlier quoted context omitted.

>In cases where an experimental therapy has at least some limited evidence (i.e. suggestion it might work) it’s quickly approved and pushed into clinical pipelines, osimertinib/Tagrisso for lung cancer is a recent example of such a treatment. I think that's the main point of disagreement. There are some encouraging cases where the process works well, and it's fair to point to osimertinib as an example. But there is a…

> Most drugs fail. But getting the drugs that do work to patients even a year earlier may be a much larger benefit than the cost of giving people with serious diseases broader choices, in addition to the current best known standard. This is contradictory. Most drugs fail, how do we identify the efficacious ones other than through trials? Depending on the anticipated efficacy from early trials as compared to existing…

>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.

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#322

Earlier quoted context omitted.

A simple way to stem most snake oil is to put all payments for snake oil treatments into escrow till the treatment is approved. Then the snake oil manufacturer can peddle their unapproved treatment to as many people as they like, but they are losing money on every dose unless the treatment turns out to be safe and effective. Obviously you need a big team of scientists on the approval panel to make sure no snake oil s…

> A simple way to stem most snake oil is to put all payments for snake oil treatments into escrow till the treatment is approved. Even simpler is to prohibit payments for these experimental treatments, but let people who whould die anyway participate in them as long as it is free for them. In return the drug companies could use the outcomes as data points towards their aproval applications. Why would a drug manufactu…

> Even simpler is to prohibit payments for these experimental treatments, but let people who whould die anyway participate in them as long as it is free for them. In return the drug companies could use the outcomes as data points towards their aproval applications.

That would never happen for good reason. Drug companies would have every incentive to bias the results towards approval by giving the drugs to detain patients. I’m not exaggerating when I say this might be the worst idea I’ve read in this entire thread.

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#323
post #254

Earlier quoted context omitted.

There's a trivial well-regulated market solution: medical company A registers treatment B with the FDA; patients can try experimental B from A on A's dime: let them out their money where their medicine is.

Exactly, a treatment should be free until approved by FDA. The team would try to make the treatment an experiment useful for science. They would have no incentives to kill prematurely patients that would otherwise have lived longer. They would work in good faith. Disclaimer: I actually had had a treatment (surgery) not yet approved, it saved my foot from amputation. This was in Europe. The doctor was adding me to the…

It should also be free after it's approved by the FDA.

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#324
post #280

Earlier quoted context omitted.

Your comment makes something that happens quite rarely (1-5% based on agent, and not quickly) seem like it happens quite frequently.

Some of these trials had double digit percentage deaths within 30 days.

Because the trials sometimes take on people with very little time left.

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#325
post #82

Earlier quoted context omitted.

> thalidomide, a deadly and basically worthless medication, Thalidomide is what is used to treat erythema nodosum leprosum (ENL) better known as just leprosy.

It used to be regarded as a miracle drug that could be used over the counter in many circumstances, and as they looked into it they discovered it just couldn't be used safely. That they've narrowed it down to some use case is more of a testament to the thoroughness of the investigation, I'm sure there are many chemicals that could treat leprosy this just happens to be the one we understand how to manufacture and when…

You are obviously deeply and aggressively ignorant about pharmacology. Thalidomide is an effective immunomodulator which is prescribed for multiple conditions beyond just leprosy.

https://medlineplus.gov/druginfo/meds/a699032.html

As with any medication there are risks and side effects but that hardly makes it "worthless".

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#326
post #49

Earlier quoted context omitted.

I remember at least three instances in my country where the authorities were forced to allow people to use experimental treatments due to media clamor. In all three instances, the result was that the treatments were snake oil and people died that might have lived otherwise. It's easy to say "people who have no other options should get access to experimental treatments" but the problem is that people who have other op…

Immunotherapies are still immature but far from snake oil at this stage. They routinely achieve miraculous remissions but also lead to many adverse events. For most late stage tumors, chemotherapy will only, at best, increase life expectancy a bit. In my opinion, the choice is obvious.

Keytruda, and other PD-1 blockers, have good science behind it. Many oncologists believe this is the true path to defeating many cancers.

While PD-1 blockers may cause the immune system to attack another part of a patient's body, we have quite a few ways to treat those autoimmune issues.

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#327
post #267

There should be a universal law in human rights stating anyone can take anything into their own bodies and governments can never, ever prevent them. Governments/regulators deciding what you can put into your body is beyond ridiculous: applies to all substances and drugs. Inform about the potential risks and effects: sure. Prevent: never.

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Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#328

My Dad was dying of IPF and I was always on the hunt for anything that may help. Of course there are countless quack "cures" but I came across a study that said metformin may help. Metformin is what people with type 2 diabetes use to help to control blood lipids among other things. My Mom actually takes metformin since she has type 2 diabetes. My Dad's doctor wouldn't even discuss it and dismissed it outright. Dad di…

I don't think the metformin trials prove much, but I agree, it could have been worth a try.

In moments like this, I think it is appropriate to find a second opinion, sometimes just to attempt something new.

Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#329
post #325
post #82

Earlier quoted context omitted.

It used to be regarded as a miracle drug that could be used over the counter in many circumstances, and as they looked into it they discovered it just couldn't be used safely. That they've narrowed it down to some use case is more of a testament to the thoroughness of the investigation, I'm sure there are many chemicals that could treat leprosy this just happens to be the one we understand how to manufacture and when…

You are obviously deeply and aggressively ignorant about pharmacology. Thalidomide is an effective immunomodulator which is prescribed for multiple conditions beyond just leprosy. https://medlineplus.gov/druginfo/meds/a699032.html As with any medication there are risks and side effects but that hardly makes it "worthless".

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Re: I am dying of squamous cell carcinoma, and potential treatments are out of reach

#330
I was an early investor about 20 years ago (nothing to write home about) for a company in this space. Small molecule therapy though, not MRNA.

Very slow going, as is all speculative biotech stuff but it made it to approvals on the vetinary side (dogs and horses) and is sold in the US for those purposes. However, I believe the human trials are somewhere around P2 currently for H&N and other indications are even further back.

Only mentioning it because I still follow the annual reports, and I know that despite having no approvals they've treated a few patients via the various avenues that are available in Australia to people who have exhausted all other options.

The drug is tigilanol tiglate. It's had some success to date, with some immune responses in distal tumors after the initial application.

There is plenty of published research available, so please don't anyone take this comment as any kind of recommendation or advice.

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