Comment by jseliger
3 years ago
In my view, patients should have a "right to try," which is part of fundamental freedom—and this is particularly true for palliative-stage patients without a route to a cure anyway. They are risking essentially nothing.
The FDA is too slow and that's costing lives: https://marginalrevolution.com/marginalrevolution/2021/08/th.... The issue is personal for me, too, because I have a squamous cell carcinoma (SCC) recurrence in the tongue, and the treatment that is most likely to cure it is still stuck in clinical trials. In other words, there's a reasonable shot I perish because the FDA is slow, in which case I'll wind up in the "invisible graveyard" that Tabarrok discusses.
They had this debate in China recently and the problem was conflict of interest (lots of pricey snake oil for dying patients who can come up with the money). The market has to be regulated even for dying people, if only to prevent scams.
Perhaps the patients should be allowed to use experimental treatments only under the condition that it is offered for free; the upside for the company is that if it works, they get the evidence of efficacy.
That would be the bare minimum in practice. That’s already the case: without premarketing approval (clinical trials), companies are not allowed to charge anything for medicine or medical devices. They’re not even legally allowed to ship them interstate until the premarketing application is accepted.
This should be the solution. If they’re trials for an unproven solution, why should they pay anything at all. I’m any case, it should be the other way around; it’s the companies who should pay the person for subjecting them to something very likely to be dangerous and painful.
In any case, I agree with the sentiment here. People should have the right to choose.
This is how it already works - this is what a clinical trial is. If you want to include the data point of a medicine working well as admissible, then you better have more than one patient try it at a time. Unless of course your drug is so good at curing patients who are absolutely terminal (like ibrutinib was). But most meds are not that much of a blockbuster. Thus you don’t know if a single patient survived if it’s because this medicine was very effective or if it was just as good as any other available treatment regimen.
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> the upside for the company is that if it works, they get the evidence of efficacy.
They don't, though. They need a control group.
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Meh, why not just let some people get fleeced...?
"Sorry, you can't buy cars privately any more -- you need a gov't agency to make sure you don't get screwed. You cannot fend for yourself, right?"
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This sounds like the best way to do it.
The company would still need a blinded control group to be able to demonstrate the effectiveness of any treatment.
However patients should be allowed to enroll for free into multiple treatment trials at the same time. For a given number of people and treatments, enrolling in multiple trials simultaneously gives more science output, and more chance of success for the participants, if you assume that ineffective treatments rarely are very harmful.
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I was going to make this point. People at EOL by default often have estates, investments, retirement accounts. In other words huge chunks of money/wealth that unscrupulous people may wish to get their hands on. Combine that with the desperation of a dying person and you have the perfect condition to create a very profitable scammer market for worthless treatments.
This also harms eveyone because all the money pouring into a treatment that was a scam from day one is oppertunitu y lost.
> This also harms eveyone because all the money pouring into a treatment that was a scam from day one is oppertunitu y lost.
You guys remember Theranos? When Safeway announced their deal with Theranos in 2012, a bunch of companies working in blood diagnostics folded because they couldn’t raise money or because their investors clawed back entire rounds.
A couple of friends had just raised a series B round to commercialize their surface plasmon resonance blood testing device, which would have actually done what Theranos promised with onsite blood testing (except with proper blood draw, not a finger prick). They were getting the product ready for golden standard testing with a CRO when investors decided it wasn’t worth trying to compete with a Theranos already in the pocket of major pharmacies and pulled the series B funding.
Patents ended up getting sold to some patent troll shortly before the news broke that Theranos was a scam.
The people who funded Theranos weren’t even desperate, just greedy. Imagine what fingers they’ll put on the scales when they’re actually staring death right in the face? It’ll be a disaster.
I think the argument is to loosen the regulation on human trials, not to drop all regulation on drug companies. They should still have to prove that they’re doing legitimate research and have had some success before opening it up to humans who are terminally ill. They should still be legally culpable for negligence and fraud.
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As a general principle, any set of circumstances which results in net increased influence of people who are demonstrably amoral with regard to the public welfare, should have as many barriers as possible put up to obstruct the success of such people.
Bad money chases out good, increasing the fraction of money in bad hands by billions or tens of billions is going to have a palpable effect on the stability of the world.
This is a very weak excuse. If preventing scams is the main concern then old people should also be banned from purchasing real estate, timeshares, large donations, perhaps even giftcards in certain quantities.
You can't have freedom without some chance of people making bad choices.
Dad asks me for a lot of money to help him buy a time share, I’ll feel ok saying no.
Dad asks me for a lot of money for a snake oil cure that might prevent him from dying from bile duct cancer in a month or two…how am I going to say no to that?
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Which is why there needs to be a process to approve experimental drugs as at least scientifically plausible.
There's a difference between something that works at least in a petri dish or mice, and something with no plausible mechanism of action like homoeopathy.
I guess it would depend on the reason for denial to a patient. If it is solely because it isn't regulatory approved yet then that doesn't seem sufficient. If the drug was provided for free from the pharma company it would be a faster path to a human trial which would be a win/win for all involved with the only possible negative for a person who doesn't have anything to lose.
That seems like a claims and marketing issue, which is entirely separate from merely producing a drug and selling it when asked. I think it's fine that the FDA regulates advertising, I don't think it's fine that they act as gatekeepers to pharmaceutical products.
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Ahhh. This answers a question I've had: I'm in the USA and one of my senators has been banging the drum for allowing patients access to experimental drugs for a few years. I have wondered why this was an issue for him. Maybe I'm cynical but this and easy PR win for him seems like good reasons why.
If they can come up with the money then who cares?
It would be a much better case for regulating if there were some external payer.
Their parents and/or kids come up with money. It is basically theft. If you are ok with theft, fine, otherwise we shouldn’t exempt it just because of the false hope it provides.
Did the Chinese government ultimately regulate the market to protect people and prevent this kind of corruption?
This wiki article is probably the best place to start:
https://en.m.wikipedia.org/wiki/Death_of_Wei_Zexi
Then there was some movement on the issue in 2019:
https://www.bloomberg.com/news/features/2019-12-10/cancer-tr...
I’m not sure where they ended up due to COVID happening next.
IIRC it did, though the cynic in me would suggest that by “this kind of corruption” what it prevents is the kind of corruption that government officials don't benefit from.
I trust the Chinese government less than I trust my own with regard to doing the right thing (just because it is the right thing or indeed at all), and that is a pretty low bar…
The regulation is approval by a governmental agency through clinical trials
There are tradeoffs here, but the current approach seems to protect people's inheritances better than people's lives.
Selling straight up snake oil is still fraud, and letting money be thrown at overhyped but ineffective treatments is a smaller tragedy than forcing people to die when treatments exist.
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The link you posted has a addendum which links to this: https://astralcodexten.substack.com/p/details-of-the-infant-...
In the more well researched followup by the same person, the author of Astral Codex, we see that the FDA did not block or slow the approval. It was that the manufacturer had no interest in even submitting a application. In fact, the FDA regularly granted usage exemptions, granted a broad exemption for research, and even directly funded one of the first trials even though they are not primarily a funding body.
The actual moral of the story maybe is that we should let third partys submit applications? It seems like there would be little risk of bad outcomes as they still need to do the approval process. It aligns incentives better as the people ultimately at risk can deploy resources comparable to their QoL improvement instead of the expected increased sales volume at current prices. There is a obvious problem that the production process is inextricably linked to the final output so a non-manufacturer has limited control and insight into a core component that introduces the possibility of regression, but it seems relatively doable to develop protocols for handling that if they do not already exist.
edit: To be fair, once the application was submitted it still took 6 years for approval. There are likely large procedural costs in doing the exemptions and testing that make inaction preferable. So, in some sense exemptions and lacking interest in approval may be problems of their own creation, but on net the overall outcome seems fairly reasonable. Actual improvements in procedural matters are likely too nuanced for a random layperson like myself to comment on.
> The actual moral of the story maybe is that we should let third partys submit applications?
The application isn't a single page form, it's hundreds to thousands of pages detailing everything about the clinical trials ranging from the success criteria for each phase, the doctors and hospitals involved in the trials, and even tiny details like how much blood is going to be drawn, when it will be drawn, and how it's going to be tested.
They're impossible to write without the participation of almost everyone involved in the process since a significant part of premarketing approval is quality control of the final drug manufacturing process.
Yes? I meant they should be allowed to run independent clinical trials and then submit for approval.
I also did point out that the integral nature of the manufacturing process is a obvious potential problem. It, however, does not seem like a insurmountable problem. The specifications on sourced components and the quality control processes applied to them is already integral to the drug manufacturing process. This would just move it one level further up where the final drug produced by some existing production process is a “component”. They also already approve drugs for different uses and evaluate existing drugs for new uses, so it does not seem that qualitatively different from some existing approval procedures. I am not sure of the exact details and am not proposing a specific solution, but it certainly does not seem to be a deal breaker.
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Not at all in the field, but are there standardized clinical trial "frameworks" that can be used in order to simplify the process ?
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Patients who are near the palliative-stage can try many drugs in the FDA approval process. The doctor has to get "permission", but that is granted over 99% of the time. IIRC, it mostly involves making sure the doctor has read up on the research, believes it is necessary to save the patient's life, and agrees to report back on the treatment to the FDA.
If there really is a treatment that is significantly better than current treatments, have your doctors talked to you about this? It was codified into law about a decade ago, but that's not so new that they shouldn't be aware of the program.
I understand where you're coming from, but as the parent of someone in the field of pharmaceutical research they have a different view.
First, human beings aren't Guinea pigs. Yes, the FDA is slow - for damn good reasons. We didn't use to do things this way and then we changed it to fix problems. There are reasons things are the way they are and it's very well-understood in the medical field. Medicine is not a move fast and cause pain and suffering kind of field or move fast and kill people kind of field. They're very conservative.
Two, since human beings aren't Guinea pigs when we do do experiments on them with drugs that have been through a very thorough and extensive pipeline already, they're looking for very specific things. This tends to make a very small population of patients eligible for a trial.
Three, trials are expensive. These aren't drugs that have been scaled-out in production. The costs tend to be exceedingly exorbitant. The medical field is very well aware of the inelastic demand for their services and this opens up new avenues for the unscrupulous to prey on people. Like the used to do in the "good ol' days."
Finally, the fact the treatment you would like to pursue is still "stuck" in clinical trials is indicative they're not convinced of the efficacy of the treatment. I can tell you lots of "promising" treatments never make it out of clinical trials. That's the nature of the beast. Most ideas are dead-ends.
My advice? Don't chase unicorns. Sadly, I've watched too many people in my family die while chasing unicorns and getting obsessed with treatments that are in trial. There are always treatments in trial. Live your life and enjoy what time you have to the fullest.
> First, human beings aren't Guinea pigs. Yes, the FDA is slow - for damn good reasons. We didn't use to do things this way and then we changed it to fix problems. There are reasons things are the way they are and it's very well-understood in the medical field. Medicine is not a move fast and cause pain and suffering kind of field or move fast and kill people kind of field. They're very conservative.
The problem with this is that they don't appear to be optimizing for the minimization of harm, which seems very obviously to be what they should be optimizing for. Instead, they're optimizing for the minimization of harm caused by new drugs/treatments/etc., while ignoring the harm caused by disease. It's all well and good to not cause suffering through your actions, but suffering caused by inaction (or slow action) is still very much suffering that's caused by your decisions.
> Instead, they're optimizing for the minimization of harm caused by new drugs/treatments/etc.
Of course they are. From an ethics standpoint they're responsible for the harm caused to you by new drugs/treatments/etc. They're not ethically (or legally - but that's another matter) for nature harming you via the ravages of disease. If you're familiar with the education of anyone in a medical or medical-related environment then you know it's pounded in their heads to do no harm. Medical intervention is to ameliorate, not deteriorate. Medical intervention is not prescribed if it's not known to heal. That's when palliative care is called for.
I will say it again - human beings are not Guinea pigs, especially when they're dying.
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The counter to this is Sam Pelzmann's "Regulation of Pharmaceutical Innovation" https://www.amazon.com/Regulation-Pharmaceutical-Innovation-...
where he shows, with statistics, that moving fast saves more lives than it costs.
Given all the human pain and suffering economists have wrought may I suggest we insist they stay in their own wheelhouse? Also, it's easy to look back, with statistics, and say had we approved a successful drug/treatment earlier then we could have saved lives. That's survivor bias as it ignores all the treatments that were found to be ineffective or worse and what those effects would have been had they been administered to a wider group earlier.
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My advice to you is that if that's your view, don't take advanced drugs, but get out of my way if I want or need to, and get out of the way of others. You can pursue your path and I will pursue mine.
They say someone who represents themselves in court has a fool for a lawyer. My experience, purely anecdotal by definition, is someone who practices medicine on themselves has a fool for a doctor. I've seen too many people die faster by bucking modern medical practices. But sure. Feel free. Knock yourself out, especially since you know more than the entirety of the medical establishment.
Sorry to read about your illness. Without knowing specifics, it is sometimes possible to get access to trial drugs via a compassionate use exemption[0].
You could find out which centers close to you are part of the trial, and contact them about getting access to treatment.
I've previously contacted a drug manufacturers directly to inquire about access via a trial center. This was for a pancreatic cancer drug made by Halozyme. The trial was ultimately halted due to disappointing results.
Please take into account that a drug still in trial may ultimately fail to meet its endpoints, as in the above case.
[0]https://www.fda.gov/news-events/public-health-focus/expanded...
Went through this for an autoimmune condition with extreme nerve pain. Support forums are full of people that say LDN is a fantastic drug and works wonders. I was on opioids begging doctors to let me try LDN so I could get off the opids. All Refused since they weren’t familiar with LDN.
I was finally able to get it online. I no longer take pain medication. Life is basically back to normal.
and the treatment that is most likely to cure it is still stuck in clinical trials.
it seems like you are contradicting yourself. if it's likely to cure, then that would be borne out by the trial? And then it would be rushed for approval. The vast, vast majority of clinal trials for cancer are unsuccessful. A 'successful' drug may add a few months of life vs placebo at a cost of $10k or more per month.
> if it's likely to cure, then that would be borne out by the trial? And then it would be rushed for approval.
I'm not sure you know how long these things take, even when they work well.
Also, the failure to show a positive clinical effect in a trial mean one doesn't exist, especially at the individual level.
On this topic here is an excellent examination of it
https://timharford.com/2020/06/cautionary-tales-the-spreadsh...
I think that patients should be able to choose, but in reality the advantage will be for them only.
Due to the lack of control groups them taking the pill does not make the science go forward (in the sense that it is an indication for the use).
I believe however that they're is a great interest in the stopping effect: the evidence that the treatment is ultimately harmful.
Still, this is a win-win:
- if the patient gets better, good for them. Does not help the pharma company.
- if the patient gets collateral negative effects, too bad for them (but they were very bad anyway). This helps the pharma company.
Coupled with euthanasia, this would be a humanitarian solution for the extremely sick.
I'm a bit puzzled why you couldn't extract useful information even _without_ a control group. Let's say we have a disease that we know that kills you. If you take the treatment and you don't die, we have pretty damn' positive evidence it works. The control group is the... You know... Many other people that don't take the medicine and die.
This is probably a good indication, but you do not know if it is the pill that is making the effect. It may also be the placebo effect.
It may also be that on day 6 you get better (no matter of you took the pill or not), and then worse on day 20, but much worse than without the pill.
Still, this is a statistical wink so to speak (paraphrasing xkcd (https://xkcd.com/552/)).
To be clear: I am all for patients experimenting on themselves when they do not have much to lose (and whenever they please, but they have to take their responsibilities then). Plus euthanasia if the experiment goes south.
IMO opinion this is an even bigger issue with other medications. Doctors shouldn't get to decide that you should live in pain, or be trapped in a prison of your mind.
In our current society, a doctor has the unilateral decision whether to end a patients life (in so far as they are able to thrive in our society). Access to stimulant and opioid medication should be a right for patients with these conditions.
We don't need a doctor to baby us, when they would certainly have access for themselves and their children. The majority of doctors would not give up their career, move in with their parents, or tell their kids that college is not for them.
> They are risking essentially nothing.
In some cases this is true, but people often want to risk their chance of survival with conventional treatments.
Since any unproven treatment has a chance to produce immense suffering, you would need to pair this with a right to end your life too. That isn't right that exists in too many places now.
What treatment is this? Atezolizumab? (I also have recurrent SCC of the tongue.)
Moderna mRNA-4359: https://clinicaltrials.gov/ct2/show/NCT05533697.
BioNTech has a similar treatment that's also been apparently slow to launch Phase III trials.
Right to try is a cruel scam:
https://sciencebasedmedicine.org/the-cruel-sham-of-right-to-...
> So-called “right-to-try” is a cruel sham that holds out the false hope of survival to terminally ill patients and their families. In return, all they have to give up is patient protections and agree to pay to be guinea pigs to test a drug company’s product. The product of an ideology that uses the terminally ill as shields to hide the ideological motives behind the law, which are to hobble the FDA, right-to-try is a terrible idea.
Wild to say this to someone with everything to gain and little to lose. What is the terrible fate you're protecting terminally ill patients from? Is it worse than death?
There are things worse than death. And then there are things that are bad when added to deaths. In the first category might be "scammers who absorb so much cash that they prevent real cures from being researched". In the second might be "people who squander their family's financial future on magic beans in futile attempt to live, but die anyway".
No one would opt into volunteer to be in the second group. But, I can see a lot of, e.g. 50-year-olds, taking a risk thinking they can refill the college-education funds and retirement funds by just working longer than they intended.
I would imagine when dying one of the comforting thoughts is that your estate will continue being able to care for loved ones after you are gone.
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> Is it worse than death?
Sure, why couldn't it be? Maybe it has severe, painful side effects. There's a reason many people with stage 4 cancer and low chance of survival decide not to go back on chemo. Maybe it kills them earlier than expected. Then what?
Historically, the protection was against death and destitution of the family when it was discovered that dad dying of consumption had mortgaged the house to the hilt to afford the overpriced opium.
With the modern social safety net, perhaps the traditional protections can be relaxed.
It's a way for Big Pharma to get cheap research by dangling false hope in front of the desperate.
Of course some here would view that as a positive.