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Comment by A_D_E_P_T | Hacker News Reader

> Clinical implications: While more research will be needed before trials in humans can begin

Why? Seriously, think about it. Most people with pancreatic cancer have nothing to lose and many of them have just weeks or months to live.

Daraxonrasib, Afatinib, and SD36 are molecules that can already be purchased in bulk, and what's the worst that can happen?

Our society's morbid, irrational fear of quack medicine causes orders of magnitude more deaths through therapeutic neglect than it prevents through safety screening. "Better 10,000 die of cancer than 1 person die of fraud/waste/mismanagement or even in failed experiments performed in good faith."

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There are already many "compassionate use" exceptions out there already. I've family friends be grated that. It helps the pharma company as well as the patient. I'm sure that will happen here.

Yeah putting myself in the shoes of someone with this disease or a loved one with this disease I would be so incredibly angry that we weren't allowed to try something when the alternative is certain death

It's the prisoner's dilemma. Or more succinctly:

Take something and possibly live, or take nothing and certainly die.

That's not what the prisoner’s dilemma is.

Yeah this is more like a Pascalian Gamble [1]. If you try nothing, then you are assured to die as God wanted. If you try something, then you might live, but then God hates you.

[1] https://en.wikipedia.org/wiki/Pascal%27s_wager

It is like Pascal's Wager but has nothing to do with "what God wanted" or "God hating you"... It's more "if it doesn't work the outcome is the same anyway" (eternal oblivion in Pascal's case, certain death in this case), therefore why not give it a shot in case it does work.

Warning to anyone reading this: Pascal was NOT a self-help writer.

I think you could mitigate some of the problems by making the drug company pay for the treatment before approval.

There is a lot of money to be made selling snake oil to the desperate, so we definitely want regulation…

So don't let people sell the drugs at a profit, at early stages.

Ding ding ding this is the way. Sell at cost. Real cost, like cost of making. NOT a cost that includes R&S amortized across the batch.

Not even cost plus? Not sure how that works, from the viewpoint of economic incentives.

It's literally free data for efficacy / later sales.

So charging patients/insurance companies at cost to fund the clinical studies?

Clinical studies today are funded entirely by the pharma companies, keep that. Selling at cost of production would be something extra, for patients who want the drugs but aren't enrolled in an actual study. The company doesn't get solid data it can use for regulatory approval, so making them donate the drugs in that case seems excessive.

A downside would be that for drugs that don't cost much to produce, patients might be less willing to enroll in the studies, given the chance of getting a placebo. That could be handled by shutting down the informal access while the study is enrolled, for anyone who's eligible. I'm sure there are other wrinkles that would need to be considered too.

Put this way, this seems reasonable. Beyond cell therapy, I don't thin the cost of drug is the motivation for not making it more freely available. 'Misuse' leading to potential liability or unjustified bad outcomes, along with some regulatory burden seems like the issue.

Oh sick, so every time my company faces an economic downturn, I can shift huge amounts of workers to a program designed to sell unfinished drugs at cost! Like, it doesn’t even have to be viable, just start selling saline with coloring or something.

Unless it does have to be somewhat viable, which is… regulation.

I'm not against regulation in principle. In this case, full disclosure of exactly what's in the drug should definitely be required. People's doctors can make informed decisions after that.

Restricting this to patients who are otherwise out of options is probably also a good idea. Pancreatic cancer would certainly qualify.

Somebody has to pay for the trial. Drugs are expensive and the amount needed to dose a single person is orders of magnitude more than mice. So who funds the study?

If it's the government or philanthropic fund, you have to put in a grant and show that it's competitive in terms of preliminary results etc.

If it's the drug companies, you have to deal with lots of complicated things with combination therapies. Drug companies don't like their drug paired with other drugs that aren't in their portfolio. They also need to see a way to make a profit on it, which means they need to evaluate whether this is the most likely successful trial, assess bang for buck etc.

If you want to go compassionate use, then you need to get the pharma to donate the drugs or insurance to cover it. This is spain, so I guess insurance is just the government since they have universal healthcare. I have no idea how that works but I am guessing it doesn't move fast.

> So who funds the study?

The End Users !!!! This is why medicine is too important to leave to drug companies, governments, or philanthropic funds.

What we need is an open source medical trial system with some bona fides

> what's the worst that can happen?

The patient dies from complications of the drug's use before the cancer.

If I had 6 months to live, and had no other options, I wouldn't care if a drug killed me in 10 days. Give me the option.

bigPharma doesn't care about that. They care about the publicity of their drug killing someone faster than the cancer.

No. No no no.

Big Pharma needs good data. And they have annoying FDAs/whatever-regulations-body slowing them down.

If you have a serious disease they might not mind you taking it. But if you have a serious disease plus your kidneys have already shutdown - w/e drug won’t save you. The death counts as a negative. “Let me take it anyway” well fine but it’s not some huge conspiracy.

It's not just those two choices though. It could be "6 months in relative comfort" and "10 days begging each minute to die but you can't because you're borderline unconscious". Or anything in between. Just saying.

Medical guidelines are there for a reason and are often, as they say in the military, "written in blood".

> "10 days begging each minute to die but you can't because you're borderline unconscious"

They aren’t going to know if it does that until they give it to a human in the first place. The only difference in giving it now is they lack a control group.

Having seen the last ten days of pancreatic cancer, there isn’t really a difference with what you’re describing.

Yes I (sadly) know. I commiserate with your loss.

Having seen a family member die absolutely horrifically in a matter of weeks due to late-diagnosed pancreatic cancer, I'd consider suicide if I got the same diagnosis.

Yes I (sadly) know. I commiserate with your loss.

Still wouldn't let my loved ones try untested treatments though, especially if it buys only weeks of extra lifetime. The potential costs are too high.

I found this green block in my back yard. It killed a dog because he was mostly cancer I think. Anyways just sign over hundreds of thousands of dollars, thanks! This will probably ki—er, cure you. What have you got to lose?

>If I had 6 months to live, and had no other options, I wouldn't care if a drug killed me in 10 days. Give me the option.

you're not being creative enough.

I agree with compassionate use cases, but be creative here : some drugs can create deaths much more miserable than the controlled burn of a 6 month descent into hospice care surrounded by family and loved ones.

6 months to live versus a possible supportive drug regiment with the side effects being constant pain until you slowly bleed out through your eyes after total sensory lock-in -- easy a choice to make? not for me.

Fine, what if the drug causes a violent psychotic break and you harm your loved ones?

What if some weird interaction sensitizes your nerves, and you spend your last weeks in incredible pain, begging to die? Not only would that suck for you, it would, again, affect your loved ones. It would also cause distress to the nurses that cared for you and the doctor(s) that administered it to you; remember, they don't just have to convince you, they have to convince medical professionals that this wouldn't be violating their code of ethics.

In a purely rational world who cares. 4 months is not all that far away from 6 months and with cancer you’d probably prefer to not be alive for those last two months anyway. We should be willing to do Hail Marys with 5-10% chances of success rather than doing absolutely nothing.

You would destroy any inheritance your family might get, or which could be donated to a cause saving a dozen lives, over a 5% chance you don’t die from cancer specifically, which might make you feel unbearably bad until you DO die? Like much worse than you already feel? That’s insanely irrational.

Edit: and all of this is before the psychological implications of knowing your time is almost up. People would rather have burnt skin removed by a painful grinder than painless maggots because bugs and being eaten are so psychologically scarring most people won’t even consider it until they experience the pain of the flesh grinder work. People won’t think rationally anyways until it’s much too late.

Sorry what’s the inheritance logic here? Are you talking about life insurance or something? Otherwise, and again presuming the cure doesn’t work which seems absent from your assessment as a possibility, how would it affect someone’s inheritance?

My general understanding is life insurance almost never actually pays out, and if it does it’s after a long fight and for less than you signed up for, and in any case should typically not be the largest portion of your inheritance.

That all aside, taking a risky but possible option that may mean survival, as a conscious and informed decision, even if aware it may void a possibility of a life insurance payout, doesn’t seem like a decision we have more right to make than the person affected by it.

Life insurance has a small 2-5% denial rate and most of those are lying big on the application. What are you talking about.

Term life insurance really isn't expensive, and it's meant to take care of those you leave behind in an unfortunate event. Pay off some big bills so your partner isn't grieving AND homeless. Most of the people on this site are pretty well-off, and can/should afford an expense like this.

If you've got a 95% chance of death, take the pain pills and enjoy your final days. Don't bankrupt yourself and spend more time miserable, dying anyways.

I think this might be a US vs international thing then on the value of life insurance (typical payouts here are around $100k, 10% or more are rejected, and that policy would be around $10k a year). But nonetheless it’s the smallest/irrelevant part of my point.

The parent comment suggested taking an experimental drug would mean they couldn’t give their children inheritance, implying that the government might seize your assets or something.

I firmly disagree with the “take the death” argument made here, but I do respect the intellectual integrity of committing to your argument at least, and suspect we just hold extremely different moral perspectives.

Are you sure those numbers are right? People are paying up to $90k to get $100k? Where is this land? I need to open a business here.

In the US, you pay like $350/year (assuming you’re, like, 30-ish?) for about a half million dollar policy.

By the time you’re 60, you shouldn’t need that payout anymore. You should have enough savings to cover your funeral, plus whatever retirement plan you had anyways to care for the probably-just-one dependent at that point.

I feel like you’re imagining that you take a magic drug which cures you and you go home happy. In reality, the drug will have severe side effects in every case, making your final days worse. The chances of it working are already incredibly low. It is a significantly more brutal lottery than scratch tickets could ever hope to be.

When you have almost no time left, you focus on quality. Visit people you haven’t seen enough, do things you wanted to do, say things you meant to say. Take some pain meds to get through the worst of it. Memento mori.

One problem is people selling their home to pay for snake oil, so their children now are not only orphan but also homeless.

Imagina an evil bank clerk on the door of a cancer center that says:

fake quote> There is a new promising [unverified] treatment that can save the life of your S.O. It's very expensive so you have to take a double mortgage on your home. You are very lucky, because today we are offering it with only a 49.99% interest rate. Do you love him/her?

Okay great point I hadn’t considered - makes the parent comment more sensible. Thanks!

Things are, at least, getting better with the passage of right to try laws: https://en.wikipedia.org/wiki/Right-to-try_law

These drugs seem to all be only allowed after Phase 1 trials, so still not quite at the level you're describing here.

Knowing whether drugs work isn’t trivial. Patients are typically very heterogeneous in their responses to drugs. For example, pembrolizumab (the most successful cancer drug ever) typically only works in, say 30% of patients depending of the cancer type. Just throwing therapeutic ideas out there and letting physicians sort out how to use them and in which patients, isn’t a panacea. Looking at clinical data can be like star gazing even in planned studies. Structured, statistically powered studies, and costly rigorous assays on biomarkers and correlative studies are essential for understanding how and in what patients drugs are working. I’m all for expanding access to drugs, and there is abundant waste and greed in big Pharma and venture, but there are also people doing hard expensive science, medicine and manufacturing. Im not sure I have the answer. A “yelp for medicine” won’t improve immediate outcomes, nor longer term understanding and progress. A great and excruciating read about the tension there is a real-time blog (the story’s story) that was written by Jake Seliger unt he passed in 2023.

That’s because we have a system that financially punishes fraud and mismanagement which is what we want and should keep.

There should be a way for terminal cases to volunteer for early trials and I believe there is already legislation that provides that but it’s not used and funded enough.

IMO, if you view your question from the ethical framework of "do no harm" i.e. the hippocratic oath instead of "move fast and break things", I can clearly see reason for the apprehension. The standards aren't positioned to catch "quack medicine" but to require full understanding before asking someone else to put something in their bodies. It's somewhat of an entitled stance that youd be okay with other people possibly needlessly dying in any circumstance for something experimental, and not one I'd ever want taken as an official stance by a regulated medical body.

Consider what the oath actually says.

> I will not give poison to anyone though asked to do so, nor will I suggest such a plan. Similarly I will not give a pessary to a woman to cause abortion. But in purity and in holiness I will guard my life and my art.

Now consider that doctors in Canada and Europe are literally administering MAID as we speak. In other words, administering poison with intent to kill. Further, consider that doctors have participated in administering lethal injections, etc. I could go on all day.

But you'd invoke the Hippocratic Oath to deny people with fatal diseases access to potentially curative treatments, though admittedly experimental? That's a funny view of the oath you've got there, and either an uninformed or very funny take on medical ethics, as well.

That's not an oath that many modern doctors will have sworn though -

(From wikipedia) As of 2018, all US medical school graduates made some form of public oath but none used the original Hippocratic Oath.

I imagine the story is similar elsewhere.

If nothing else, it's not the only hail mary you could potentially go out on. Would you give up the potential of being part of a trial for a drug that has actually done the work and demonstrated real promise in various pre-trial tests just to take a gamble on this alternative which hasn't even had the initial test replicated yet?

Further there is the potential for a false negative. If they don't understand enough about how the drug would work in humans, they may trial inappropriate doses or delivery methods. If those don't help or make things worse, it could be mistaken for the drug being ineffective and lead to the whole line of inquiry being abandoned. Then not only do you die, but countless others are potentially harmed by an effective version not being developed.

Finally, cancer treatments aren't just for the terminal. Drugs which primarily help during the early stages by necessity need to be trialed on people who still have a chance, maybe even a decent one, going with other, well established treatment options.

We might take it too far, but the fear of quack medicine is extremely rational.

Every time I see homeopathic medicine on the shelves in a pharmacy, I think we’re not taking it far enough.

Every time I see homeopathic medicine on the shelves in a pharmacy, I think we’re going to need 100000x more

> Our society's morbid, irrational fear of quack medicine

It is not an irrational fear.

Brandolini's Law applies: "The amount of energy needed to refute bullshit is an order of magnitude bigger than that needed to produce it."

The only way to prevent quackery is to cut it off hard before it gets started.

Wakefield demonstrated the disaster that happens when you don't.

(And if you have been reading this site for very long, you know the experimental treatments are already around--we're not currently lacking for possible cancer treatments. The problem is finding the trial. Then the problem is getting people through the process and then getting them to the trial. See: "Please be dying, but not too quickly": https://bessstillman.substack.com/p/please-be-dying-but-not-...)

Even if I grant that argument, what I've described isn't even quackery. It is legitimate medical research and experimentation, and what doctors in olden times would call a "heroic" intervention -- but, sadly, now this sort of thing has become collateral damage in the war between medicine and quackery. And patients are the ones who die and suffer because of it.

The general public, as a group, cannot identify quackery. People died from bleach and horse dewormer to prove this. The continuing career of Mehmet Oz also demonstrates this.

There will always be more malevolent actors looking to take advantage of people than there are benevolent actors able to protect them. Standard rules and laws are an attempt to at least protect the majority of the people the majority of the time. Like anything, rules are never perfect, and you have to weigh the limitations against with the benefits.

As someone who has literally trawled the cancer trial databases for people, lack of trials is not the main problem--finding the appropriate trials, on the other hand, is terribly difficult.

If you really want to help people, apply AI to help common people search all the public cancer trial filings to connect up the patients and the doctors. That would do far more good, far faster than changing laws and rules around last ditch experimental treatments. You won't become rich, but you'll help medical science a lot, and you might even save a life here or there.

good news, are current FDA has many ways of fast tracking a treatment and a willingness to do so

I had a relative who died from this around 20 years ago. 50yo slim, sportive and healthy and after going to a diagnostic as she didn't feel good, she was gone within a few months .. So yeah, if there is even a slight chance it works, this should be tried and that'd save people :(

The ethics of life and death are murky at best. When is it acceptable? 6 months to live? 1 year to live? 5 years? What is the cut point? The answer is, there isn't a clear answer. Yes, that is a cop out, but it is also true. I agree with allowing people of sound mind to make informed healthcare decisions towards the end of their lives that involve high risk. but I would be wary of weakening the process too much. We should have a push-back because people in these positions are exceptionally vulnerable and therefore easy to take advantage of and, even worse, likely to be unable to defend against abuse for very long. Weakening this process would likely lead to drug companies doing what they always do, abuse their position for money. Why even go to expensive traditional trials? Just give some promising, cherry picked, results in a press release and now people are coming to you signing every waiver and paying their last penny to live next to the trial that will kill them because the drug wasn't even close to ready. I would likely feel very different if I was near death, but that is the point isn't it? Again, I'm not saying this shouldn't be an option. I just think it needs a lot of scrutiny and a high level of skepticism.

Ethics is a topic I would never trust HN on.

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