Comment by tux3

To sibling commenters: immunotherapies aren't the only problem. There are a ton of truly evil companies out there pushing therapies that do not work, have never worked, and will never work, because they literally have no possible mechanism to ever do anything. This is a crime, but it's very very hard to prove.

And these companies get very good at gaming the system, because that is their product. They are mechanisms to commit fraud, stealing all their patients' money and all their families' hope. This is a very bad thing. And, no, I am not making any of this up, but I dare not name names here. These companies also tend to be litigious!

The impact of this is extremely severe. First, people die because they choose a truly worthless treatment that can never work, over bad ones that at least had a snowball's chance. Second, people lose faith in The System, because they think that the fraudulent treatments should have worked, so they lose faith in the good ones too. And third, R&D efforts can get redirected away: rare condition X already has a treatment, so let's put our efforts elsewhere (oh wait, no it doesn't, that was fraud, now there will never be a treatment).

We will not untangle the experimental treatments issue until we confront this problem. Just do not think that it is all in "good faith" here, or even "best effort": there is real fraud going on, committed by monsters that know exactly what they are doing to take their profit.

> 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 options want those too, because nobody wants to go through chemotherapy or whatever.

I reserve for myself the right to try to save my own life, even if that means some people who can't handle that responsibility make things worse for themselves. I can't get from, "but other people might hurt themselves" to "therefore you simply have to die, sorry."

No, I think we just have to be straightforward about this; I don't want anybody to purchase snake oil, but that possibility does not move me to eliminate options for myself or my family.

Just because a treatment doesn’t work doesn’t make it snake oil. Snake oil implies intent to deceive. Untested drugs can be based on a strong theoretical foundation and still not work. I expect the majority of experimental treatments won’t work. We should be trying regardless, not just for the sake of the people taking the treatment, but for the countless people in the future who can benefit from the same treatment when it does works.

Also we should stop patronizing everyone. If someone understands the risk and their doctor agrees, just treat them.

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.

I'd say that people should be allowed to try whatever treatments they agree to have, in order to save their lives, and also in other cases. One cannot say with a straight face that a woman has sovereignty over her body and thus contraception and abortions should not be banned, and preclude that same woman from getting a treatment that can possibly save her life but has not been approved yet.

Yes, and the FDA often does get pressured into approving treatments of dubious efficacy: https://arstechnica.com/science/2021/06/a-disgraceful-decisi...

It's easy to understand the logic of desperate patients who will try anything but it doesn't seem right to allow manufacturers to profit hand over fist selling treatments that may not even do anything, or worse, outright cause harm.

> In all three instances, the result was that the treatments were snake oil and people died that might have lived otherwise.

It seems like you're claiming that people who were given medical treatment after media attention weren't down to their last option(s)?

If they were down to their last options, then they made their choice and it didn't work out.

Couldn't this be solved by getting doctors' opinions? If docs says "This person's only chance of survival at the moment is chemotherapy, and it has a good chance of saving their life.", then, refuse the experimental treatment.

But if the docs say "With our current medical knowledge, this person is destined to die within $TIMEFRAME.", then, if the patient consents to try anything, even if it kills them earlier, why not?

Do you have the citations for the three instances where "people died that might have lived otherwise."?

In this person's case, he will not live otherwise, so he has nothing to lose by trying an experimental therapy, although it appears to be too late anyway. Very sad.

I guess the FDA has a role in minimizing the market for snake oil.

>but the problem is that people who have other options want those too

So, why can't one go through its own choice of treatment? Disregarding if its a good choice or a bad one.

That is an interesting and relevant point, but it does not apply in case of Jake and others like him -- he has no alternative where he might live.

In my opinion, the FDA ought to be more open to allowing experiments in cases where it is clear the patient is aware of the untested nature of the treatment.

It would result in tragic cases like the three you describe. During COVID-19 it would have resulted in people taking Ivermectin which was ineffective and even harmful.

But during COVID-19 it would also have resulted in determining 6 or more months earlier that the vaccines we made were safe and effective and the number of lives saved in that single instance would have greatly outnumbered the losses from 100 years of experiments.

Maybe the fact that these are the ones you remember is an indication of the problem, rather than evidence that it is wrong.

So, observing a problem is no more complicated than becoming aware that it exists. That's the only interaction necessary to invoke ethical liability. How does then pretending you didn't observe it release you from anything?

So, you would flip the railroad switch to kill only 1 instead of 5 helpless people?

>I think the solution is to invest more into medical research now,

The author is arguing that terminally ill people (with a few months left to live) -- like him -- would be willing participants in trials to help medical research. They already know that mRNA drug or whatever likely won't cure them. It's possible some new scientific knowledge of the drugs' effects can still be gained even when it doesn't cure them.

Given the realistic odds, the primary purpose (from society's perspective) of letting of terminal patients participating in unproven drug trials would be medical research rather than "Hail Mary cures". From the patient's perspective, of course they hope it improves their health.

> we’ll know that we at least we made significant effort, and gave everyone a better chance, rather than settle for a “Hail Mary” drug near the end.

I think this is a sensible take for someone who is not facing their own imminent mortality. But no matter what we do, the game theory of terminal diagnoses means there will always be incentive to go for a Hail Mary in the end.

>How often do these drugs, etc turn out to effective?

This is a big point a lot of people ignore. I feel terrible for the author, but if there hasn't been a single drug invented so far that has any real chance of curing him, it's extremely unlikely that this one out of reach drug is going to be the drug that can save his life. I don't really know much about medicine, but I'm pretty sure that progress is usually incremental as well, so you start out with drugs that cure some patients and work from there instead of having some massive breakthrough.

Just "invest more"?

Who does the investing? Not "The Market". The incentive isn't to cure but to treat. The Market wants (repeat) customers.

The government? At least, in the US, we've been dismantling the government's ability to do this since at least Reagan. Even our so-called Liberals aren't pushing hard here. You'd have to look to the "fringe" Progressives within the Democratic Party to even come close.

And why? Because "fuck you, I've got mine" may as well be the national motto of the USA at this point.

People will bristle at this, certainly. Look at Biden: he's done so much!

Biden is no FDR. We need a real social safety net in this country. And, yes, we need a "right to try", even if it means waiving malpractice rights in those cases.

People are, perhaps understandably, very eager to advance at a faster pace, always a faster pace. Nowhere is that more evident than in the case of people facing death regardless, but in addition to the issues you raised (early failures can lead to even worse delays) there are other ethical concerns. Terminally ill people are often understandably desperate, and I would be too in their position, no doubt about it. Their families are desperate, often their doctors are desperate. That doesn't mean that their remaining life doesn't have value though, or that cutting it weeks, months or years short isn't a problem.

I think that's often lost on people, and in a more frightening way, people who are all-to-eager to use the terminally ill as ultimately disposable test subjects for unproven treatments. If it was JUST down to safety then I could see the point to an extent, but as you said efficacy is a big open question too. Of course if you're facing death then you may well want to roll the dice, but the question there too is how well you really understand the odds. The understandable implication in a lot of the discussions around this issue is that if only regulators were a bit faster, people like the author wouldn't die.

The reality is grim though, most of these experimental drugs and therapies are not effective, regardless of whether or not they're safe.

3 years ago we wanted to rush the COVID vaccine and it probably saved millions.

I don't understand why we can't let people make risk reward judgments. Yes probably more people will die, but they were not forced.

>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 good case to be made (although various blog posts likely state it better than I could in a comment) that the current process introduces enough delay that the opportunity cost is higher than the risk.

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.

No one is advocating we just let people die, but there's an argument about the cost of delaying therapies and the cost of giving people choices that warrants careful consideration. While proven therapies are good and snake-oil is bad, improving standard of care for everyone historically saves many more lives than sticking with what we know for a longer period of time.

Uhh, given recalling defective toys or car seats is a pretty straightforward way to prevent further injury, isn’t that a pretty good trade off over knowingly potentially causing more injury just to save money?

How would you feel if your child was injured by a car seat that had a defect the manufacturer completely knew about but refused to recall for the sake of saving money?

You had me to a point. And then you began the usual conservative dog whistles.

"Words are violence"? If you were dox'd, would that be violence? Or your life threatened? Or those you love? Or just people who look or love like you? Where is the line? Wherever you personally believe it should be? No.

Moreover, if a terminal cancer patient wants to commit suicide, they can legally do so on several jurisdictions. Why then, can they not instead opt for this treatment as an alternative to suicide?

"First do no harm" sounds good on paper, but it fails the trolley problem. It leads you to harmful beliefs like "we should not use the AZ Covid vaccine to save thousands of lives because it might cause one person to die of blood clots".

The problem is that in the real world, it's extremely rarely the case that you can make an intervention that only has benefits, and doesn't have costs, so honestly applying "do no harm" is paralyzing. The medical ethics field understands this, but often the administrators/regulators are way too conservative.

A better model that generalizes without special-casing is "weigh costs and benefits, and be conservative but bounded about unknown risks before making an intervention". In this case the potential downsides are 1) the patient dies which is irrelevant because they are almost certain to die anyway (and they made the informed decision to take this risk), and 2) some reputational damage to the FDA and medical practice if it's seen to be "preying on patients with no other options".

I think 2) is being weighted way higher than it should.

The problem with this model is it requires an understanding of statistics to determine what is ethical and just, and many doctors don't even know how to properly reason about false positives/negatives, let alone the lay public. Yet members of the public aren't willing to forgo their outrage on a subject that they cannot actually conceptualize.

In some sense we are getting the regulators we deserve, not the ones we need; the FDA is probably rationally and correctly evaluating the political risks, media attention, and public backlash around allowing this sort of case.

Off label prescriptions are legal and very common.

The requirement to test for efficacy and not just safety was only added in response to Thalidomide (which disaster had nothing to do with testing for efficacy). So what you're asking for is very not radical.

You can get get experimental drugs/treatments that aren’t approved by getting them under the clinical trial for that drug. The question is who pays for it? Cancer treatments are millions of dollars.

This can cause all doctors to require it, and this has happened across industries, for example, software and internet platform "terms of service". It is a very bad idea.