Be kind and good to your loved ones. Life is short and no one knows how much time we have left. While the FDA’s antiquated bureaucracy does no good, the true enemy is the disease itself. I believe in science and I hope that someday no one else will needlessly suffer as my brother has.
This is the real reminder for young people. Every single one of us is one tiny cellular mishap away from an untreatable, agonizing demise. Be KIND to one another, because when it is your turn to die, you will have wanted to have had a positive impact on the world and those around you.
Stabbing backs to maybe get a pay raise will mean nothing to you or your family. It's just one more person who won't honor your temporary existence.
I was a student of your brother's at the University of Arizona for a semester. It was over a decade ago at this point, but I think it was English 109. It's hard to explain how humbling it felt to chat with him one-on-one. He struck me as a genuine, intelligent, and friendly guy who was worth listening to.
This is such terrible news and I wish Jake and yourself the best.
"We need to have a much stronger “right to try” presumption"
Quite.
I'm now four years older than my mother was when she passed away after two really exciting years. I can't remember the exact description of the killer but "squamous" was involved. Radio, chemo, surgery bordering on butchery etc. Bout one seemed to be in remission and all clear sounded only to be rescinded a few months later, second run was a negative outcome. Faith healer for a laugh "but you never know" - mum wasn't daft but when you are out of reasonable options, you might as well invent a few more!
However, there is still hope whilst breathe still flows and there is absolutely nothing wrong with hoping for a miracle. They do sometimes happen. Keep fighting and kicking and being a pain and only give up when it is obviously hopeless.
Lost my brother to a carcinoma, a disease that most likely will be successfully treated, cured and even prevented in my lifetime. I feel for your brother but also for you.
While I can't comment on this particular case, I sincerely recommend Americans to explore treatment options for treatable diseases in other countries - like India, South Korea, Cuba (?) etc. - that have excellent doctors and decent healthcare infrastructure. They may charge foreigners a bit more than the locals, but you will get better service that is unlikely to bankrupt you.
(Not sure about Cuba's current healthcare infrastructure).
I would hate to ask the author this, as it seems cruel, but is the FDA denying him access? As he points out, Moderna has two drug trials going. The FDA "right to try" page[0] clearly spells out that Moderna could give him unproven medicine currently in a clinical trial under the right to try laws. So Moderna could let him into one of the two studies, or give him the medicine under the right to try laws if it rejects him.
Likely, Moderna doesn't want him to take the drugs because they will probably be ineffective this late in the cancer stage. It doesn't want its treatment to be associated with his death.
Actually the Moderna trials are recruiting metastatic and treatment resistant disease. From his description he has not met inclusion/exclusion criteria for the studies due to treatments received and not received rather than being too advanced in stage.
It's highly highly highly unusual to be offering an experimental therapy on compassionate grounds when conventional options that have potential to actually work well haven't been tried yet. In this post he only describes locoregional therapy and it appears he has not tried anything systemic yet.
The closest I've seen is we at least try a very short attempt of something in clinical use and then say patient refused/intolerable side-effects/treatment failure and move on. I can't imagine a circumstance where medical ethics would allow to skip a trial of validated therapy for something without even phase I data. It's not like this mRNA by Moderna is known to actually work.
Are there conventional therapies that he has not tried that could be effective? It seems he has never had chemotherapy, but he implies at this point that's a long, almost impossible, shot.
I think the issue is that Moderna just doesn’t have much incentive to do it and it’s more a distraction than anything. But yeah it could also just be too late. My dad was recently in a similar position, but by the time he theoretically could get his hands on the drug, he was too weak too handle them.
I feel somewhat closer to this person because I was once in his position as a child fighting a neuroblastoma in 1981 and some how my mother found a way to get me on an experimental list which saved my life. Half of the kids that took the drug died by the time they were teens due to heart failure, obviously I wasn't one of them, but am thankful for the chance to live a full life.
When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning. That's something our government has forgotten about or doesn't care about. If I was in this persons shoes, I would make it as personal as possible against those in control of the FDA. Show up at their houses, work, kids soccer practice, get in their face and let them see what their inaction is doing in person.
> When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning.
I agree with you. But the FDA would ask you to rigorously define "slightly higher chance of winning" -- and prove it. In the event you cannot do this, they believe that letting you try an experimental drug would be more unethical than letting you die of neglect.
So I'd rephrase that statement of yours: "When the odds are against survival, there shouldn't be any rules limiting treatment, regardless of type of treatment or odds of efficacy." ("When the odds are against survival" can be quantified, e.g. a 90% chance of dying within a year.)
I am not yet done thinking on this area, so my thoughts here are incomplete, but thay said:
Would this not also open the door for any snakeoil salesman to prey on what might be medically "hopeless" cases?
If I am ever diagnosed with something currently uncurable, but there are experimental stuff in the works, of course I'd like a shot at those experimental drugs, but I hope that me/my family would also not squander whatever assets we have on snakeoil, in which case I'd rather my surviving family was not impoverished in the fight.
I assume that, at least partially, this is why regulations in this area were put in place to begin with.
Before anyone shows up at FDA decision makers' kids soccer practice please consider things from the point of view of an FDA decision maker. They have to make a choice which they know will lead to both type 1 and type 2 errors. For life saving medicine, when the decision isn't clear, both type 1 and type 2 errors are awful. It's likely they already feel the burden of responsibility.
Category A - approved by the FDA, basically what we have right now
Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Category E - experimental and basically limited run from pharmaceutical companies. These essentially need to be tailor-made or produced by a GMP kilo lab. There are plenty of drugs in this category - I worked on them - and the intended recipients are entirely animals, QA, and regulatory agencies. But maybe if some crazy S.R. Hadden type (billionaire in Contact) wants to guinea pig themselves, let em.
The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
> Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
We can already prescribe off-label if the FDA has approved it for at least 1 indication, and it mostly gets reimbursed.
> Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly. The US is the largest market for manufacturers so they almost always start here.
> Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Pharmacists and physicians are ethically bound to prescribe to the best of their ability and avoid harm, by prescribing something only validated in animal models it means we are not prescribing/dispensing something validated in humans and therefore not meeting or exceeding the standard of care.
This sounds like a recipe for killing people.
> The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
Huh? There are many ongoing gene-directed and mRNA studies being tested.
Do you know what else sounds like a recipe for killing people? Not allowing people to access therapeutics that might save their life because it hasn't yet gone through regulatory approval yet for whatever reason (delays, too expensive to submit), etc.
> There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly
LOL. What are you talking about. There are so many examples.
One of the most tragic is amisulpride. Amisulpride is an antipsychotic medication used to treat schizophrenia and other psychiatric conditions. Some key notes about its regulatory status:
- Amisulpride was first approved in France in the 1980s and is widely used in Europe.
- It was never approved by the FDA for use in the United States, and at this point there's not organization that can afford to go through the approval process because there's no patent.
- The reason often cited is that the manufacturer did not apply for approval with the FDA. It was likely not considered commercially viable for the US market at the time.
- Amisulpride is believed to have comparable efficacy to other second-generation antipsychotics like olanzapine and risperidone, but with a lower side effect burden according to some studies.
- In Europe, amisulpride is considered a first-line treatment option for schizophrenia, but American psychiatrists do not have access to it. According to some sources, it is literally recommended as the best antipsychotic in other countries.
There are "right to try" laws both Federally and in 40+ states. It's unfortunate the author doesn't address those, I'm curious how they interact with his case.
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.
One aspect of the problem here is the difficulty in running a clinical trial, particularly at the recruitment stage. The covid-19 trials all had a surfeit of participants because of a pandemic, but with modern cancer treatment trials the qualification requirements significantly cut down on the eligible population.
This, in itself, isn't a huge obstacle. The problem is the state of healthcare data systems. It's next to impossible to perform high-quality search (even by individuals approved to do so by the IRB). The state of the art in most places is regex searching in SQL.
This is something we have the power to contribute to. Bringing modern search capabilities to important datasets like health (while maintaining HIPAA-conpliance) is a much better use of engineering time than mining spyware data for creepy insights...
[Disclosure: I contributed heavily to one of the major medical search products on the market. We dealt with organisations that expended tens of thousands of dollars and many months per candidate for recruitment. Using some very straightforward IR tech we literally found all their candidates in a few minutes, plus many more. But there is so much more to do!]
Yes, very true. Beyond just access to clinical data there are often major differences between how the same conditions are recorded between different provider organizations based on EHR data models and local practices. Researchers who want to use data from multiple organizations typically have to put a huge amount of work into their data pipelines for cleansing and normalization. Some standards development organizations such as HL7 (including their various FHIR accelerators) are now writing more detailed and specific implementation guides to improve data quality and consistency so I would encourage technologists to contribute to those projects.
There seems to be a growing sentiment that FDA delenda est, but if we don't fix the underlying problem that led to this situation, it will just come back.
As the author says, no one ever blames the FDA for the people it failed to save. But approve something without the certainty that it isn't potentially going to kill someone, and there will be hell to your doorstep.
Even if you want the experimental treatment, you cannot get it. Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault. This is sometimes also known as the Copenhagen interpretation of Ethics.
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 options want those too, because nobody wants to go through chemotherapy or whatever.
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.
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.
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.
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.
For those who are curious, the term was coined on this blog post[1]:
> The Copenhagen Interpretation of quantum mechanics says that you can have a particle spinning clockwise and counterclockwise at the same time – until you look at it, at which point it definitely becomes one or the other. The theory claims that observing reality fundamentally changes it.
> The Copenhagen Interpretation of Ethics says that when you observe or interact with a problem in any way, you can be blamed for it. At the very least, you are to blame for not doing more. Even if you don’t make the problem worse, even if you make it slightly better, the ethical burden of the problem falls on you as soon as you observe it. In particular, if you interact with a problem and benefit from it, you are a complete monster. I don’t subscribe to this school of thought, but it seems pretty popular.
The post provides real life examples of government programs, nonprofits, and individuals being criticized for helping in the “wrong” way.
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?
This has been a common complaint for decades. We always want to try rush experimental drugs/procedures that “show promise”.
How often do these drugs, etc turn out to effective? 25 years ago we wanted to rush gene therapy and that didn’t turn out well. Someone died. It probably set back gene therapy:
I think the solution is to invest more into medical research now, then when we, or someone we know, eventually ends up with some horrible disease, (cancer(s), Alzheimer’s, Parkinson’s, etc) 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 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.
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.
> Even if you want the experimental treatment, you cannot get it.
Says who? In terminal truly no-option diseases (e.g. glioblastoma multiforme) it’s pretty easy to get access to experimental therapies on compassionate grounds.
The challenge in this particular case brings us to:
> Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault.
This is a false dichotomy. What’s unethical is offering experimental therapy with ?? effect when there are evidence based palliative treatments (e.g. conventional chemotherapy) with proven overall survival benefit.
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.
No one is advocating or suggesting we just let people die.
>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.
There's this overabundance of the need for safety that's overcome society.
It's as if we can't assess tradeoffs anymore.
You see it with the lack of children playing outside - even though random kidnappings are almost a nil risk and that they're more likely to get by a car.
Defective toys. Defective carseats. Millions get recalled for a failed few.
You saw it with masks. You see it with speech, "words are violence".
Everyone wanting the illusion of feeling completely safe.
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.
Experimental treatments often are very expensive, I believe require a lot of study of the patient and so on ...
It's not like a magical pill(s) you take an go home and live or don't and everyone says "well he consented so he took his chances". The entire process of experimental treatments is hugely expensive.
> Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault.
If a train is coming with someone pinned to the tracks, and they are begging you to hand them an axe so they can remove their own leg-- knowing they may die from blood loss, do you just do nothing?
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?
It's a high worth debate, maybe there's a ethics curve.. for most cases you have the normal "don't do harm" but for life threatening you need another board to remove some stops without letting the scams proliferate.
"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.
> Even if you want the experimental treatment, you cannot get it.
fortunately, Baja California seems to have everything. Or specifically, a different drug approval strategy that is right in the middle of this.
The FDA's main limitation is that it gives a one to one relationship in approvals. A substance is seemingly evaluated for a single narrow ailment. While evaluation process is a threshold of side effects as well as efficacy in treating that single narrow ailment. This process could be expanded to recognize that fulfilling the side effect issue could expand its use in other ways, more easily than whatever semantical distinction of easier the FDA uses now. There could be more possibilities for one to many approvals.
Going on a tangent here: there's a reason medicine is heavily regulated—because of the lessons we've learned the hard way. The same reason law is also heavily regulated. Some of these lessons have become obscured by time, unfortunately. Other lessons may not be fully applicable to the modern state of the field. (I say this as a qualified doctor and lawyer with some appreciation of the history of both fields.)
Are the current regulation regimes perfect? No. Would we be better off without it? I doubt it. Should we try to strike a balance between regulation and innovation? Yes—but doing so is devilishly tricky. No matter what you do, someone somewhere will be unhappy.
> Even if you want the experimental treatment, you cannot get it. Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault. This is sometimes also known as the Copenhagen interpretation of Ethics.
Most people (myself included) would not agree to that. Experimental treatment should be made possible - at least if there have been promising results with previous studies (animals, small trials etc.). There must be a safeguard, however, to make it impossible to sell false hope to dying people - because they will pay for everything, even if it does more harm than good.
I think it could be ethical to let people try experimental treatments in the context of a phase 1 clinical trial, ensuring that something is learned from the attempt. However, I have also heard that an issue with that constraint is that connecting patients to clinical trials is a huge logistical problem that has not been well-solved.
It actually seems like the kind of problem that could be a good fit for tech: have a registry of clinical trials, make sure it’s widely known and consistently used. I don’t know much about the problem, though, so I don’t know if or whether that’s unrealistic.
> Even if you want the experimental treatment, you cannot get it. Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault. This is sometimes also known as the Copenhagen interpretation of Ethics.
Interesting. Thanks for sharing the "Copenhagen interpretation of Ethics". I've thought many times about this problem, didn't know it had a name.
Comes to mind Dante Alighieri: "The hottest places in Hell are reserved for those who, in a period of moral crisis, maintain their neutrality."
I still think they need another category than what they have now.
My understanding of the current categories of drugs are you have "banned" and "has this specific therapeutic effect that costs billions of dollars to prove".
A category of "this doesn't kill you" in the middle would probably alleviate most of this. Insurance only has to pay for things with proven therapeutic effects, but you can shield people from poison and get a lot more data way cheaper by having his middle category.
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.
I think what really drives me crazy is that the FDA approval can limit me taking something.
Put simply, If you believe “my body, my choice” then the current regulatory system is pretty messed up.
To be clear, I’m fine with the FDA existing as a labeling body. Sure label something FDA approved. But don’t limit what we can take because it’s not approved.
Otherwise, you end up with cases like this and many others, where an industry can easily be regulatory captured and ensure competitors are slow or unable to enter the market.
It is (a very rational) approach for administrative workers, who get little credit for getting things better, but are at risk when they can be taken accountable for something terrible.
That way, for example, in Germany, there was a halt on the Astra-Zeneca vaccine after a few cases of thrombosis per million. For comparison, it is one in six for COVID. The halt, most likely, caused many deaths. Yet, these deaths "have happened". If there were a death because an administrative organ didn't take action - the organ would be considered responsible.
For the matter, Pontius Pilate was an administrative worker. And his incentives were aligned accordingly.
In the language of the Trolley Problem, it is doing nothing (no matter how many are there on the tracks) or (even better) finding a way to pass the lever to someone else.
The FDA could create a standard consent form for nonapproved treatment that patients and doctors would sign, which would indemnify the physician from legal repercussions, but they don't, and they bear full blame for that. The AMA would still have its own regulations about the limits of ethical experimentation, with the revocation of a medical license as punishment to serious offenders, and malpractice safeguards could still be there. State laws about gross medical negligence are also an option.
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.
Imo the whole US medical complex needs competition from a small but sophisticated libertarian state without any of the regulations that formed the present system, and I think it will happen. The market demands it, and the world would be better off with some competition. Most likely it will begin with some small nation that sells anti-aging therapies.
There are companies from which you can order bespoke mRNAs. Lead times vary but are in the weeks. Many are abroad. The other components of mRNA vaccines can be assembled by someone with 2 years of biochemical Ph.D. experience. There are no laws against a person assembling and injecting themselves with anything.
I have extra sympathy for the writer of this article, since mRNA vaccines (even if they were a random sequence) are relatively lower risk than many other sorts cancer interventions which are FDA approved. I happen to be an ex-professor, who is a director at a drug company. I know that if I were the unfortunate author of this article, whose heart is in the right place. I would probably be injecting myself with my own janky version of whatever offered hope.
Whether that would actually change my prognosis? Probably not. I can say though that I _would_ and I believe others are entitled to positive freedoms I'd afford myself.
The author seems to forget that entering a trial doesn't necessarily give you access to the treatment. You have as many chances to be in the control group receiving a placebo.
And as bad, sad and frustrating as it sounds to someone in a desperate situation, it is for the greater good of many more human beings, protecting us from snake oil.
Right now he has a 0% chance of survival. If the experimental treatment is at all effective, the probability of not being in the control group multiplied by the probability of effective treatment is greater than 0%.
The probability of a more painful death is also greater than 0%. So it the probability that something could go wrong and cause publicity which would interfere with the testing or approval of the drug and affect other people's access in the future*. There are always tradeoffs.
*this person takes the drug. Two days later they die of a heart attack. Was it caused by the drug? How many resources should be spent to determine that? Should that death be listed in the potential side effects? What if the news story publishes an article and scares people off from the trial? What if it's later proven that the drug had no effect on the heart attack but the distraction from it delayed 10,000 people's access to the drug?
> The author seems to forget that entering a trial doesn't necessarily give you access to the treatment. You have as many chances to be in the control group receiving a placebo.
This is untrue, in this case.
Typically, only some phase 2 and phase 3 trials are randomised; the treatments that the author refers to are at an earlier stage of development and so not in either of these phases. All patients will receive the active therapy.
It's also worth noting that for cancer trials, while new treatments in these later phases may be tested against a placebo, it's never just a placebo - that would be unethical. If the new treatment is an add-on to an existing standard-of-care treatment, then they'll receive the standard-of-care treatment in the placebo group. If it's not an add-on, then it will be tested directly against the standard-of-care. If there isn't an established SoC, it can sometimes be approved without a randomised trial, if the results are good enough.
To note, the placebo group is typically getting the best current existing treatment. Rather than nothing. Although in some cases the best treatment is still nothing, which sucks.
It is against medical ethics for the placebo not to be the current standard of care, and experimentally it must be… If you can’t beat the current standard of care then your drug isn’t effective.
The greater good argument is repugnant in this case. He is going to die, and deserves an opportunity to do whatever is possible to save himself, including new and little-tested, and likely ineffective treatments. He literally had nothings to lose.
And in this case he would be actively helping humanity as well by being a test case. We would all gain knowledges and information from his treatment, if he could get it.
There's a very easy regulatory solution: Roll the drug approval process back to the way things were done prior to 1962. Back then, safety testing was all that was required. Efficacy testing -- which is difficult, expensive, arguably unethical in itself, and in some cases effectively impossible -- was not required. Drugs cost ~20-50x less to bring to market, and were brought to market faster. Indeed the 40s and 50s are still known as the pharmaceutical industry's "Golden Age." And it wasn't only because of low-hanging fruit.
Pair this paradigm with extensive postmarketing surveillance and periodic reviews for efficacy in a patient population. These could be done at two years, five years, and eight years -- and approval automatically rescinded if safety issues arise or efficacy is close to null.
Give people with fatal diseases a "right to try" drugs that haven't passed safety testing -- and use that data.
Yeah, right. They had such advanced cancer medication back then.
> Give people with fatal diseases a "right to try" drugs that haven't passed safety testing -- and use that data.
That data is practically worthless.
I'm in favor of having people try out medication, but it will need to be heavily regulated. And we know what happens to regulation: a party comes along that doesn't like regulation, or gets bribed, and the regulation goes out the window. It's a good way to start another opium crisis.
This is the reflexive response to every common-sense proposal to roll back the regulatory burden.
I'd raise a couple of points in response:
First, Thalidomide was never approved in the USA -- for safety reasons. The mechanisms that were in place at the time did their job.
Second, the response to Thalidomide was overblown and indeed downright hysterical. "Better to let 100,000 people die of neglect than allow one person to suffer an awful drug reaction" is not rational policy.
> That data is practically worthless.
Enough "practically" worthless data, and you get somewhere. It's a matter of quantity. Obtaining "hiqh quality" data is often unethical in medical practice.
> Say you're a runner. In the beginning of your competitive career, you get the most gains by becoming a better runner. And then at some point, you get more gains by shooting (or bribing) the ref.
generally, insurance companies do require efficacy. many of them have decided not to cover aducanumab for that very reason. though this also gives insurance an additional excuse to deny stratospherically-expensive gene therapies and other life-saving new treatments, since even the most effective new drugs won't have e.g. 10 year survival rates until they're a decade old.
I do think that people should have options, especially when there aren't effective treatments, but it's not exactly simple. In most cases, any treatment you pick has the opportunity cost of other treatments, and for life threatening diseases that opportunity cost might be living. Very few, if any, patients are going to be in a position where they can legitimately evaluate the effectiveness of treatments. In most cases, I don't expect health care providers will be in the position to do that either- even most specialists will be treating a wide variety of conditions, and may have relatively little experience with unusual diseases. Even in the best case, this is assuming that drug companies would actually try to make effective drugs rather than looking for other avenues to sell ineffective drugs (or drugs that were only accidentally effective)- I don't that in today's environment that's at all a reasonable assumption. Ultimately, the information asymmetry is vastly weighted in favor of the drug companies, and the cost is lives.
That's how it works in Mexico. You only need prescription for antibiotics (makes sense as their abuse would create a public problem) and psychologic related drugs (I dont agree with some of them like amitriptyline... ) .
But other than that you can get almost anything even buying it online and get it at home in the next 3 hours.
For those that don’t know, the 1962 change is the Kefauver–Harris Amendment, which was a response to one of, if not the, largest overall global crisis of conscience in the medical field. From Wikipedia: “When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness.” After some time it became increasing obvious that while it worked, it caused birth defects in pregnant or soon to be pregnant women, with its manufacturers actively trying to quash the information about such cases; again, from Wikipedia: “Use of thalidomide in pregnancy can cause fetal abnormalities such as phocomelia (malformation of the limbs). In males who are taking the medication, contraception is essential if a partner could become pregnant.”
Thalidomide disfigurements were disturbing. Children born with these disfigurements were not linked to Thalidomide until much later. Thalidomide was in fact not allowed a safety regulation by the FDA initially. It wasn’t until the company producing it, Grünenthal, pressured the FDA. You see, the FDA reviewer for the medication was leery about it after some reports had floated over her desk about a possible remote risk that this could potentially cause birth defects. Grünenthal’s international licensee to the US refused to explain multiple papers that linked Thalidomide usage in pregnant women to birth defects.
As it turns out, not only had Grünenthal known about the issue they had actively worked to silence the information, a ploy that worked until a major change in leadership in Germany.
It was denied usage in East Germany.
For a longer documentary on the subject and how it changed medical safety testing, Plainly Difficult has a very good video on it: https://youtu.be/Vi03zz6eCik
(Note: I am explicitly ignoring the context that the Thalidomide development program was run by an actual Nazi who was responsible for unethical and frankly awful experience on unwilling human subjects in concentration camps. If anything, it only amplifies his concern to hide adverse effects, which he did quite successfully until the company was given what can only be considered “A slap in the face”.)
There are 469 studies for that type of cancer that are accepting males of his age, of which 260 are in the US, on that site. Obviously, many are going to be inappropriate, but hopefully with something is available to him.
What I don't understand is why the FDA doesn't automatically rubber stamp approvals on medicine approved in Canada and the European Union. We all know their medicine is good - so why can't I get it?!
Money and politics. Why can someone drive for 6 months in a country with a foreign driver's license but can't get a local license?
I've had this misdiagnosed medical condition for 25 years by multiple doctors. Nothing serious but extremely annoying. There are approved drugs in Europe for decades which are much better than the ones approved in North America. One day the company making the drug that's approved in North America decided to stop making it! You just could not get it. This was the event that finally led to the correct diagnosis for my condition because I was in so much pain I got to see the expert. Turns out my condition has a very simple non-prescription solution and for 25 years I've been taking the wrong meds that happen to alleviate this different condition as well!
So I am good but this condition is not uncommon. What are all the other people that really need this drug in North America doing?
I'm not sure what's the takeaway here. Maybe that efficient/smart organizations generally don't exist. This is just a reflection of human nature.
If you're okay with it, could you expand/name the condition you thought you had, the actual one, and the medication(s)? Never know, might help someone else out
Why can someone drive for 6 months in a country with a foreign driver's license but can't get a local license?
A government issued id, like a driver's license, is often required for various services like opening bank account, a telephone connection, avail some government service etc. Thus a local driver's license can be used for deception by a foreigner who wants to pretend to be a local citizen.
Because it then becomes a kind of race to the bottom, where all manufacturers will approve medecine in the easiest country, a bit like flag on convenience for ships
They already do that. Having approval and data in another country makes it much easier to get FDA approval. But it's still a lengthy process, costs a lot of money, and often puts you in competition with other options that are approved. There are drugs that have been used for decades in Europe, are perfectly safe and proven to be more effective, and are not available in the USA (and likely the other way around, I'm just aware of specific examples there).
But that’s the problem. No regulatory body has perfect judgement, so they’ll all approve some harmful things and ban some helpful things. If you’re so strict that you don’t allow thalidomide, you’ll also ban stuff like beta blockers for an extra decade, causing 80,000 deaths. The argument in favor of loosening restrictions is that it would reduce overall death and suffering.
Sure, but they did rubber stamp Fen-phen and Vioxx despite plenty of people within the FDA understanding it should come with a black box warning. The FDA needs a win that's more recent than 1971 if they want to demonstrate their efficacy as regulators.
I guess we know that, but why doesn't the EU rubber stamp medicine that's approved in the US? In my opinion it's actually good for there to be independent bodies reviewing things.
There are many divergent if not contradictory regulatory findings levels and limits between the US Canada and Europe.
eg. Tolerable total cholesterol levels US:200 Euro: 240 (last I checked, these move around quite a bit. In the 70s the US banned Cyclamates as an artificial sweetener, but approved Sacharine while Canada approved Cyclamates and banned Sacharin.
For Glaucoma treatment Europe is "Laser first, drugs second" while the US is Drugs first, laser surgery second.
etc etc.
Somewhat famously the US not doing this stopped Thalidomide being such a large issue in the US, but of course one example of it failing doesn't mean it is inherently bad policy.
So all drugs will always be trialed at the most lax country and get approved at a stricter one? Then why make rules because the laxest country will be the one used and in control of approvals
This quote sounds like self interest in the article, but there is more to it:
> If anything goes wrong,” he argued, “think how bad it will look that we approved the drug so quickly“
People who take an approved drug are relying on the result and authority of a scientific process — across all drugs. Some scary results and people may start to fear the process, which may end up killing more people.
That said I’m sympathetic to his plight and think that he sounds like a candidate for the compassionate use program. Any result would not help approval as who in such a program would volunteer to be randomized into a placebo arm? They’d just plead in a prior human administration disclosure section of any NDA.
(Also, pragmatically, immunotherapy grate nets are customized and extremely expensive. Who will underwrite it? Not the drug company who would have nothing to gain, not the insurance company, and I doubt the patient could afford it).
Part of what they do is they match patients with clinical trials for whom they would be candidates and then facilitate the process on an on-going basis. Apparently this bypasses a number of bureaucratic hurdles which can be faced by patients; for example a patient receiving care from a particular research institution might not be informed about trials being conducted by other, non-affiliated institutions.
Naturally, there's rather more than this to them, but this part sticks out in my mind.
And finally, take what I'm saying with a bit of a grain of salt because I am remembering from casual dinner-time discussions that I had some time ago with my friend. My memory might be bad, they may have changed what they do since I last talked with my friend about it, etc.
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 died in 2021 and I find it difficult to think metformin may have helped him live a more comfortable life. I know it's not a cure but the research seems to indicate a significant improvement for anyone with IPF taking metformin along with anti-fibrotic medications which Dad did take. We should have just used Mom's metformin really Dad had nothing to lose but it's hard to see that at the time.
When I read the original story and this metformin one, I'm so glad I live in a country where I basically can walk to a pharmacy and by most drugs without a prescription.
I can buy 60 slow release 500mg tablets online for about $10 usd and they'll send them to my home for about 1 extra dollar.
Fuck the government, fuck their controls. If I or someone I love is dying, I'll make sure to try ANY and all options, even if it has a slight chance of working. Everyone has a right to fight for their live.
After COVID (both the disease and the vaxx), I got heart arrhythmia, I had around 5000 irregular heart beats a day (PVCs and PACs mainly), and those all happen in a matter of hours, so when they happen, it's pretty debilitating.
After a while, I invested in a Bluetooth stethoscope and ECG watches, the doctors finally believed I have something. However, the cardiologist's advice was to learn to live with it, because it's completely harmless and in young people, ablation, beta blockers are not worth the risk.
Having these irregular heart beats is a very uncomfortable feeling, so I was looking for articles about the root causes and potential treatments.
After trying a couple of things (both pills and lifestyle changes), I found an article that says arginine and taurine reduced the number of irregular heart beats in their experiment. I tried it out and I have basically 20-50 irregular heart beats a day. When I stop taking them, the irregular heart beats come back.
Now, I know I'm doing something that is potentially risky, but to me it is worth it (and I reduced my dosage, and I try to quit using them every couple of months).
* it's not really quack science as the science is real, just that me applying it in my situation was not recommended by a doctor
I had a similar presentation: sudden 1-3% PAC load at rest following an asymptomatic COVID infection. Cardiac MRI showed minor residual scar tissue. I noticed my diet was pretty seriously deficient in magnesium, and after starting a supplement the abnormal beats have nearly vanished.
I read this, and while I felt immense sadness, I will obviously move on with my life soon enough and forget about it. I wondered, if I were ever in the same situation, and someone read what I wrote before dying, they might empathize for a bit, but then they'd move on as well.
I just really wish that there's something beyond death, that there's something out there, and that all the suffering and unfairness and randomness in life is not for nothing. I hope we someday truly figure out what the fuck we are doing here in this universe. And if not that, at least we reach a point in biology where we have the ability to solve a lot of problems of the mind and body and make life better for everyone.
When there is nothing beyond death, there is no death. We won’t be sitting on the sidelines blindfolded. We won’t exist. From our perspective the death never actually happens.
I’m surprisingly okay with my lack of experience of the billions of years before the earth existed, and I won’t experience the billions after.
That said, just because we can’t stay at Disneyland forever, we might as well go on the rides while we are here.
We are all dying. Some sooner than others. As a student of philosophy, this perspective has driven me to avoid the common status concerns that many people chase.
All though you're correct it is rational to not fear death. I personally, and likely many other people here, have a very very strong aversion to it.
I DO NOT want the cessation of experience.
Ideally, I'd like to continue in perpetuity, to see the sun rise from Venus, or visit my tenth generation offspring on Saturn.
All of those missed experiences would be deeply saddening. To see our species conquer to universe, to see intelligent life bloom in the darkness of space, that is the goal.
I'm not overly concerned about death on its own (I feel it's going to be kind of like being asleep), neither am I that concerned about my role in the universe. Instead, I feel more for people who truly suffer in life maybe due to poverty, or due to disease, etc. who don't get to go on Disneyland rides. It makes me feel what was the point of it all? It has to be teaching us a lesson beyond the "simulation" and if not -- that's what makes me sad -- not my personal fear of death, or anything to do with status.
And even to a lesser extent -- why do we suffer -- is it a law of physics that can't be bent? I don't agree with people who believe more pleasure equals more pain. There will be people who live amazing lives, and those who don't. And so I feel that we as intelligent beings can reduce randomness, and take control of our environment and make sure we can all go on Disneyland rides at least to some extent, and hopefully eventually figure out what's outside of Disneyland.
Let us say that there is nothing beyond death, does that really mean that life is ultimately pointless? I'd argue that the idea that there is nothing beyond death is what makes life all the more meaningful. We are only going to get one shot at all of this, we better make it count.
From this I derive the motivation to work hard at what I do and ultimately try to contribute to the problems we face as a species before I pass. It also makes me appreciate the raw human connection that we can all experience: love, passion, friendship.
I may not be the one to light the altar of discovery that allows us to say, cure cancer or become a spacefaring species, but I will proudly carry the torch and pass it on.
You can philosophise yourself into just about any position: death is real & life is meaningless, death is real and life is meaningful, death is but a transition & this life is meaningless, death is merely an illusion and life is meaningful,
I believe that Jesus is Lord, and everyone who seeks him finds him.
Matthew 7:17 - "Ask and it will be given to you; seek and you will find; knock and the door will be opened to you."
I was given a very clear sign 17 years ago, not when I asked God to prove himself, but only incidentally when I was seeking his guidance on something; it's nevertheless lasted as an undeniable proof for me. Though, it's better to believe without seeing.
John 20:29 - "...blessed are those who have not seen and yet have believed."
Acts 2:38 - "Repent and be baptized, every one of you, in the name of Jesus Christ for the forgiveness of your sins."
Disclaimer: I do not identify with American/political 'Christianity'.
Wishing is one thing. Hope is the better thing. There is something beyond death. I don't know how anyone can think otherwise. Who else has the words of life?
I agree more/most folks ought to try them under the right circumstances (yada yada mental health caveat here), but I also know plenty of psychonauts who are complete pricks, even some who have broken through on DMT and are still complete wastes of oxygen as humans. Go figure.
They are a doorway to new perspectives. You still gotta internalize the message.
The drug supposedly helped delay the doctor's cancer and extend his lifespan until he stopped taking it, then it came back "with a vengeance" and he passed away. He wanted to stop taking it to verify whether it was actually working or not.
I wonder if it might help this person? He might have to be on it for life though.
Don't take my word for it though, this is FAR from my field of expertise.
This is an mTOR inhibitor, I believe there are others already in clinical trials. I know PIK3 inhibitors are used to block some cancers. Most inhibitors stop cancer for "a while" but cancer cells have the ability to circumvent pathway disruptions.
A steel-man response would be that assisted suicide is more about pain reduction, whereas experimental drugs could have terrible side effects.
It isn't a convincing argument to me, because possible death avoidance is a higher level of morality to me, but harm reduction is extremely prevalent in medicine as a driving factor.
There is a clear problem, and a good idea here. (i.e. Right to Try) What needs to happen to make this move forward?
I am getting so mentally exhausted learning about a specific problem, and then experiencing the helplessness of not knowing how to push on driving towards some mutually agreeable resolution.
Add in the fact that there is no way to seemingly coordinate the push towards a resolution. Individuals taking action without coordination feels just the same as taking no action at all. Are there any tools to coordinate the push and keep track of progress?
What about the right to refuse? I don’t think there actually is a problem here, there’s no reason for this Pharma company to provide an expensive untested drug- only potential negatives
I saw both of my parents go through cancer (they both, so far, survived), my wife has MS - so I was quite interested in the "perspective" treatments.
You have the whole usual bunch of idiots that will advertise magnetism and cosmic rays to cure you, then new treatments that may or may not be available in your country (but available in others) and finally the trial ones.
I discussed at length with an acquittance of mine who works in the clinic trial branch of a pharma and she first gave me the usual double blind trials explanation (which I am aware of), but then could not really answer why the pharma companies insist in not having people, for free, that would test if the treatment is not obviously lethal (or heavily impacting).
If I was faced with the perspective of dying soon (or going through something like Alzheimer) I could not care less if the treatment is fatal to me. Again: not that is not working (this is something one can assess statistically through normal trials) but that it is clearly harmful.
This would at least be a clear indication of "don't try it" (or "be very careful monitoring for this and that")) if there are enough patients who react badly
Regulators are, in general, too sheltered and disconnected from the impact of their actions.
Incentives matter. When you get to make decisions that impact others, but not feel any of the costs associated with that, you do not have the correct incentives. I hope the staff of FDA read this and can’t sleep tonight. We can hope they feel some emotional pain, even if it is only some small subset of the pain they have and continue to cause to others.
I would disagree with this. Regulators that I have worked with in US and EU knew what it meant. Maybe not the most amazing technical people I’ve ever worked with, but they were as competent as any random sample of pharma/tech types. Their jobs is to verify that you have completed all the valid documentation to demonstrate that your drug does what you claim it does. Their opinion on personal emotions are irrelevant. They are supposed to be guideline checkers.
I understand some people are checking boxes, with no space to consider their impact. Please generously reinterpret my point to extend to their management stack and the political establishment that is responsible for the system.
Those who establish, support and tolerate that system should be as directly exposed to its consequences as practicable. It is good for them to see these stories and feel the consequences of their decisions.
I think the consideration that an article like this misses is the unintended consequences of speeding a process up / reducing the criteria for review, approval, etc.
I think we can all see incidents of where some oversight process is loosened because of some legitimate desire to help some, but then you learn that the bad / incompetent / exploitative actors come out of the woodwork to test and take advantage of the changing of rules. Not even saying intentionally, but just by sheer numbers, the change you made allowed things that were being held back by (hopefully proper) regulation to now happen.
Anyway, not saying that the FDA and other bodies couldn't move faster -- that is always the case. And there will always be examples of people/cases stuck in the cracks with legitimately sad situations.
But I would hope that people reading such stories think about why there is a process. It's not like the FDA's purpose in life is to stop people from benefitting from new treatments. It's to prevent the flood of bad effects of companies/individuals from being able to say they offer some drug that doesn't work in the way it says it does.
>I think the consideration that an article like this misses is the unintended consequences of speeding a process up / reducing the criteria for review, approval, etc.
In general I feel like the sick should not be held responsible for the unintended consequences of things. The principle that it is better for 10 guilty men to go free than 1 innocent man to be punished applies here as well. How many suicides have happened because it took this long for the use of psychedelics and THC for the treatment of depression and PTSD to be approved (partially, in some places). How many people are suffering today, right now in pain or under the care of doctors they would otherwise leave for poor treatment but the "opioid crisis" has limited their access to the treatments they need? I've faced this problem personally more than once, and while I am sympathetic to the law of unintended consequences, I just can't be convinced that it is the duty of myself or my loved ones to suffer because someone else might abuse something. There is a balancing act to be had for sure, but any borderline case should ALWAYS err on the side of reducing the current actual harm in favor of preventing a nebulous potential future harm.
If he's going to die why not give him the option to try medicine that is developed by large players with a good reputation? Weighing historical success into the process seems to make sense to me. Beta programs from Google are usually very functional...
Some FDA APPROVED cancer medication cause many severe side effects, for example, Opdivo/Nivolumab[1], my father used it and it seems to help, but caused other long term side effects, which seems will never pass.
1: https://www.opdivo.com/potential-side-effects
Another topic for discussion related to this (and I hope we can be detached enough to discuss the intellectual side of this impersonally):
Even if the drug/treatment method were approved, how much would this cost, would the author even be able to pay for / have the insurance company pay for the treatment?
And by the way, what limits are there on the price of a drug that an insurance company or the government will cough up the money to pay, for one person's extension to life for a couple years?
If someone has a very rare or just very advanced cancer, how much should the rest of us (as individuals paying taxes/premiums/etc) be on the hook for paying for last ditch efforts to prolong that person's life?
These are genuine questions I think are legitimate to ask, if not in polite conversation, then at least at the level of policymaking bodies in govt or insurance companies. I'm sure that people in the UK are quite familiar with this concept or debate.
You cannot just say you'll pay whatever it takes to save someone's life no matter what the circumstances.
The FDA is not bad. The world has never had a shortage of liars, scammers, or snake oil salesmen. The term snake oil itself hearkens back to salesmen who would promise "medicines" to desperate people to con them out of their money.
Allowing trials to be bypassed and allowing people to pay for early access to unproven drugs would bring a flood of such be vendors and be bad for society, bad for medicine, and bad for ethics.
No one is advocating for "pay for access" or a means of bypassing trials that facilitate a "flood of [scammers]", so this is a straw man. You'd have to show why any design for relaxing regulation of trials is necessarily bad in aggregate.
The article even cites a case where the bureaucrats are confident in the safety of a trail drug but unable to approve for political reasons.
Not to mention the FDA allows plenty of snake oil supplements, etc. to be sold, so it's not particularly good at the goal you claim it's optimizing for.
This is a very interesting question. Why are medicines regulated federally? As I understand it (and IANAL) doctors, pharmacists and nurses are regulated on a state by state basis.
It would be an extraordinary disaster to kick that regulation back to the states.
Florida would probably outlaw all mRNA technology. Their FDA would refuse to approve any mRNA-based therapies, and so on.
We have seen the disaster that approach can cause in healthcare, insurance, abortion (reproductive health broadly), gay rights, etc. It's insane that we have state by state drivers licensing as an example that is merely highly inconvenient.
It's not a good thing that doctors and nurses are regulated at the state level. It's a horrible thing that contributes to the US healthcare system's vast dysfunction.
I hope more and more medicine/science moves outside the reach of FDA. If someone is willing to pay for a treatment (or recreational product), and is reasonably informed/competent to decide the risks, and it's not a risk to anyone else, go for it. If someone tries to prevent consensual commerce (possibly while wearing a silly uniform or carrying a printed ID badge from a state), violate the law if on balance it's worth it to do so, and if it were literally my life at risk, I'd use whatever force required to accomplish the transaction. Hopefully treatment would be on the table before I lost the ability to run a carbine properly if needed.
Medical tourism is an excellent opportunity for "network state" and state alternatives. I already get virtually all elective medical care outside the US for commercial and service quality reasons, despite having US insurance.
I mostly go to expat/tourist-focused high-end clinics in Asia (there are a bunch of options; mostly depends on which country you're going to be in -- Thailand, Singapore, Japan are particularly strong). You can get a really comprehensive physical (cardiac calcium, exercise stress test, imaging, comprehensive blood panels, multiple doctors/specialists, etc. for <$1k -- something comparable in the US would be $5-10k (e.g. https://my.clevelandclinic.org/florida/departments/executive...). I travel enough for work that I can just go a few days before/after a meeting or conference, so no incremental cost (maybe an extra day or two of hotel).
I do carry Blue Cross/Blue Shield PR coverage ("PPO Gold", $230/mo), although it doesn't cover anything outside of PR except for emergency care. I should probably get a secondary insurance plan (which might include full coverage outside the US, or might even include shorter visits to the US as well), but for now I'm comfortable self-insuring medical costs, particularly since I think I could get insurance negotiated rates in the US even if they're paid out of pocket.
Better quality, lower cost, than anything I've found in the US. I live in Puerto Rico, which has particularly bad medical care; if I lived in Boston or SFBA I'd possibly have a local doctor, but I haven't found anyone in PR, except for expat friends who are neurorads/etc., who is a competent doctor. "Have a pain? Get on a plane" is the plan, and I have medical evacuation insurance, an ALS bag in my house, etc. for that.
The other upside is my records remain under my control; they don't get put into some weird insurer/employer accessible system protected only by laws. I can request/receive raw files and keep them myself.
(So far, I don't really have any serious or chronic conditions besides being overweight and slightly high blood pressure, but if I had a screening discover cancer or something, I'd want to have full flexibility on how to proceed with that.)
(Relatedly, I've deferred getting a dental implant for a failed root canal since right before Covid, so currently looking for the best dental implant medical tourism option -- Mexico, Colombia, and Asia are all pretty solid. It's 3 visits (plus possibly orthodontics since it's been so long with a missing molar), but internationally is maybe $2-3k vs $5-15k.)
There is some important context for the following comment:
“If anything goes wrong,” he argued, “think how bad it will look that we approved the drug so quickly.”
In the 1980s, when the comment was made, there were still people at the FDA who remembered the Thalidomide disaster, which would have been a lot worse had the FDA approved the drug. In the U.S. several thousand women took thalidomide during the clinical trials, and some doctors took it, too:
In one case, a doctor had been using thalidomide himself and prescribing it to his wife. In addition to the wife’s loss of vision, the doctor mentioned peripheral neuritis, nerve pain that is a side effect of thalidomide.
The other report is even more alarming — a nurse had given birth to a baby without arms or legs and, as a registered nurse, “she may have had access to the item.” (1)
Other countries including Canada, Taiwan, Japan, and West Germany did approve the drug or allowed it to be sold.
On December 2 1961, the drug was taken of the German and British markets, after several doctors brought up concerns as it appeared more and more plausible that thalidomide, when taken by pregnant women, was responsible for severe birth defects. Thought the Government of Canada was informed of these suspicions about the possible teratogenic effects of thalidomide, we had to wait until March 2 1962 for the Canadian authorities to react and, in their turn, withdraw thalidomide from the market. As unbelievable as it can appear, thalidomide was legally available in Canada for three full months after being withdrawn from its origin country. (2)
Gets complicated, fast, when you start considering the legal concept "of sound mind and body" - why it exists, what it means, when and where it finds use... For a good historical case, Jonestown.
"Regulation" vs "Information" also gets complicated, fast, when you consider global supply chains - for recentish news, checkout the stuff on heavy metals in Trader Joe's chocolate - how does all that information propagate to the final consumer? How does that consumer have the knowledge, skills, and time to process it?
(As with all things, IMHO, it's about balance, and, IMHO, balance comes from forces in opposition. "You are the ultimate authority on your body" is one force.)
Without socializing of medical costs I completely agree. But if you are asking other people to pay for a part of the consequences of your decisions then you should accept that those other people can constrain the decisions you can make.
I also know from Google Scholar, that copper increases IL-6, penicillin breaks down into penicillamine, used to treat Wilson Disease, a copper metabolism difference, and I also know that Omega 3's look promising for reducing IL6.
The problem with your scenario is when the consequences are unknown.
People who aren't in medicine really have a hard time understanding just how grisly the things the human body can go through might be.
Medical staff saw during COVID the mismatch between the degree of fear the average Joe had about the consequence of intubation and the degree of fear and panic of the average Joe when actually getting a tube down their throats.
A drug that goes wrong in a bad way can go REALLY wrong in a bad way. Dying from cancer sucks, but it's still several degrees less horrible than dying from your CNS being eaten away from an autoimmune response to an experimental drug which somehow leads to opiate-resistant neuropathic pain.
But if we simply caution "we don't know if this drug will cause horrible side effects" versus "this drug may likely cause unthinkable pain that we can't control in your last conscious moments" that's a very different level of informed consent.
You might be surprised by the number of doctors who privately lament how patients and patient families in general will so often choose to shoot for low odds outcomes that mean terrible conditions for the patient in their last months of life. Even when risks are known, people tend to be bad at actual risk assessment, and will downplay risks and focus on potential rewards, and this extends into medical care. And I'm skeptical that descriptions of what might go wrong versus actually seeing firsthand what it looks like when things go wrong still represents adequately informed.
So while in spirit I agree that completely criminalizing personal choice around consumption is not ideal, when there's insufficient data for truly informed consent I'm not sure I still see eye to eye on the topic.
I mean, fentanyl? Obviously it's a whole subject that could be unrolled/debated, but I don't have any interest in doing that today. Really, I thought I'd just point out one interesting and often unknown aspects of US/State law (assuming this is mostly a US-based forum; I know you said universal human right) - taking drugs isn't a crime anywhere that I'm aware of. Possession of them certainly is, but just having taken them is not.
It should be legal too. I'm not defending the use of it in any way, this is not about drugs but a more fundamental problem: governments deciding what you can and cannot put into your own body.
They should inform people about potential dangers and effects of substances, and try to prevent the underlying reasons for people to, say, do heroin or fentanyl.
But if someone wants to do it anyway, making it illegal just makes things worse as people will be stigmatized socially where they should be welcome/accepted the most, and they'll obtain the substance illegally and dangerously (who-knows-what-it's-laced-with and exact actual dosage) anyway.
So just inform and support the people but make it legal and relatively safer to consume for harm reduction.
But if someone wants to OD and kill themselves, I mean, it's sad but it's their own body and their own life.
> anyone can take anything into their own bodies and governments can never, ever prevent them.
Thought experiment: There is a magic drug or parasite where any dosage (whether deliberate, accidental, or fraudulent) will force the person into a single-minded violent quest to get another dose.
For the next month, another hit is the most important thing in their world, even if that means selling everything they own, cutting off their own leg, or murdering their children. Repeated doses cause mental confusion and are eventually fatal.
Are you still comfortable saying that nobody can make any law against the distribution or consumption of THAT substance?
Not OP, but laws against distribution? Absolutely.
Laws against consumption? A terrible idea.
What we should want to do as a society is funnel people interested in trying things we think they really shouldn't do towards legal chokeponts that are less onerous than DIY access under controlled distribution but still allow for attempts at prevention of the end outcome.
The clearest example of this even more than your drug scenario would be a drug that just immediately kills the user.
There's a lot of people every year that seek out that end result. While some can fall under a narrow scope of legal options under dignity laws when faced with terminal situations, there's many who seek out that outcome without physical ailments.
If there were a legal way to seek it which was overall less traumatic of a route, but which was also only on the other end of intervention measures like counseling, how many lives might be saved as compared to the rather ineffective prohibition that we see today which largely fails to prevent access and use, but whose illegality does prevent aspects of both research and prevention that might otherwise occur if distribution was the only thing targeted in laws and not attempted consumption?
If people are aware of the life ruining consequences of a drug but value their own lives so poorly that it doesn't deter them from throwing them away to seek out a drug, then society doesn't have a drug problem as much as it has a human experience problem.
There's few things more cruel in concept than ensuring people keep living under conditions where they'd rather not live at all. Whether they are seeking that result all at once or gradually throwing their life away, criminalizing their seeking rather than the conditions that motivate their seeking is wildly messed up.
I would like this, if somehow the people giving you the things were required to do it for free. Because without that, it just looks like writing a blank check to fraudsters.
It doesn't matter if insurance companies aren't required to pay for it. People will max out credit cards, borrow from friends, and mortgage their house. All for something that could sit anywhere on the continuum of: does nothing to kills you immediately. Probably with a side of "did this rather than something that would have actually worked".
Devil's in the details. Suppose Pfizer wants to test a new acne drug based on radium nanoparticles fused to asbestos. It might work, and hey, if you can give a homeless guy $100 and a bottle of vodka to "voluntarily take it into his body" and let you watch to see what happens- that's so cheap! Why not give it a shot!
Should be, yes, I agree, however, we are extremely far from this, I don't even know how many hours I would need to travel to legally buy and smoke a pack of menthol cigarettes.
Agreed. The regulations are beyond ridiculous and definitely not for the greater good of the society, only to clear the names of bureaucrats and regulators.
I am so sorry for what's happening to this man, and I hope he finds peace in his last days.
the economics, ethics, and effectiveness around early approvals are really difficult to manage. companies have a strong incentive to get earlier approvals. but once the cat is out of the bag, it's hard to get it back in. if a sub-standard drug makes it to market and gains wide adoption, it makes later drug trials of more effective drugs really hard. where's the outrage for potential beneficiaries of better therapeutics?
I don't mean to say this man and others shouldn't get a chance at a hail mary when they're staring down death. just, it's risky business for others in the future. I hope the best for him and others.
And if your willing to consider alternative therapies there is fenbendazole(see joe tippens protocol). It’s a dog dewormer and is available at pet stores as panacur-c.
Things don't happen in a vacuum. It’s understandable that people want access to the experimental medicine for themselves or their loved ones when the fear of god has been put into them. When one has nothing to loose, what’s there to loose?
Unfortunately it’s our dignity (or at least others diagnosed with „x remaining months“). As soon as this becomes normalized, the moral impetus will change that those wo didn’t make it, probably weren’t brave enough to try the new stuff.
(not an MD) The FDA does allow for compassionate use of experimental drugs. My understanding the many early stage drugs are tested this way, but access is limited to trial centers. The author should try search drug trials database to see there's a group that is recruiting: https://classic.clinicaltrials.gov/ct2/results?cond=Head+Nec...
My brother is a physician who is working with patients in drug trials. He had the very good fortune to see an experimental drug successfully treat a very sick, critical patient who was declared a candidate for "compassionate use".
In what ways does always letting individuals choose to take an experimental drug not work, if we make sure they know what is known and what is not? They are desperate, and that's a horrible place from where to make a decision, but dying is a really bad alternative.
What are the pitfalls that would allow for this to not always be the option? How would this go more horribly wrong than just letting these people die?
If it were for science alone, it might be fine. The problem is when Steve Jobs is sick and I walk up to him and sell him an experimental cure for $2,000,000,000. He can trivially pay it, but I have a huge incentive to lie. At a smaller scale, a more efficient conman can take all of someone's assets. And not just the dying person's. How many people wouldn't sacrifice everything to save a spouse's life or their child's?
The other concern is when you turn down medicine that might work for snakeoil that doesn't.
The lying seems like the problem there. Present the patient with accurate records of previous trials and outcomes, let them make an informed decision (with help from their doctor, if they're not scientifically literate) and I don't see a problem.
Could the former be fixed by requiring experimental drugs to be free of charge, or would that break how drug roll-out works? Somebody suggested an escrow account in this thread, which also seemed interesting.
Not having some level of “right to try” is abhorrent.
Having said that there are two elements that I’m not quite sure how to adjudicate 1) where does one draw the line with regards to how sick someone needs to be to qualify for right to try, and 2) how do ensure that patients are actually getting a treatment with some resonance likelihood of success as opposed to some snake oil?
I thought the recent New Yorker article on FDA's drug approval policies, "When Dying Patients Want Unproven Drugs", was balanced, insightful, and well-written. It covers Thalidomide, and focuses on ALS and HIV. https://archive.is/u6vmI
> think how bad it will look that we approved the drug so quickly
The media (both traditional ans social) owns a large chunk of the underlying blame, due to their rush to create simplistic narratives in the wake of anything that "goes wrong" without nuance or examination of tradeoffs.
Unclear to me why clinical trials seem unavailable to him, which is how he would gain access to these treatments. The major cancer centers generally will have options for his exact situation, though sometimes they require he finish conventional and salvage treatments first.
I understood your question to mean “why can’t he have access to clinical trials?”
A person has to qualify for the clinical trial by meeting a set of specific set criteria to ensure the results are interpreted with the least amount of error.
He wrote "The FDA was loathe to approve initial mRNA human trials". The implication seems to be that if not for this added delay, this potential treatment would be further along.
That doesn’t make a ton of sense, because there are plenty of phase 1 early stage trials at the largest medical centers in the country that use pre-“FDA approved drugs“. The whole purpose of the early trials is for the companies to go get FDA approval.
If he said he went to Mayo, MD Anderson, Harvard, Sloan Kettering, and none of the trials were available to him that would make a little more sense. But a great number of the trials in his disease site are for treatment refractory patients, so it’s pretty surprising there’s no apparent trials for him.
This is blaming the FDA for lack of treatment, not the recentness of the treatment.
That all the MRNA treatments they refer to are in trials tells you everything you need to know: we don't know which work, we don't know how effective they are, and we don't know what they work on.
It is possible to enroll in trials for these treatments, but as they say they "may" be denied as they're so far along. But that's what you want: if a trial takes someone on who would be highly likely to die even if the treatment works then depending on the trial size it's possible that that one patient might skew the results such that the treatment is denied, or alternatively, another person who applied for the trial gets denied even though they had a higher likelihood of survival.
I can understand it being incredibly hard for this guy, but we have been through the alternative:
* Snake oil treatments: drugs that do nothing but bankrupt people
* Actively harmful treatments: drugs that literally make things worse, while bankrupting people
* Paid trial scams: you can pay to be part of a trial, which immediately allows for the above two despite a regulatory environment that ostensibly requires trials.
etc
Things like the FDA exist in response to prior actions, and once they've existed for a while, people forget that the only reason that they don't seem necessary, is because they are there. Much like the "unnecessary" financial regulations that were removed, and immediately resulted in banks creating the Great Recession.
Hence, it is not possible for the FDA to create a "patients can be 'treated' with untested treatments" loophole that is not trivially exploitable by the kinds of people that resulted in the FDA existing in the first place.
Ok, so how do we fix this? Can we put this community into action to fix this problem?
This is after all a group full of hackers. I don’t know this domain area, but isn’t there anything we can start or do to change this obviously stupid and immoral system?
3. Accelerated drug approval gets mired in advertising. The general public has no idea how to judge if a drug works or not. Plenty of people believe that homeopathy works. The FDA gets massive pushback when trying to take a drug that is worthless away, because people think it works. This hurts us all and creates an incentive for companies to hide data and deceive customers.
4. The FDA is as fast or faster than the Canadian or EU equivalents. The FDA is not specifically slow, bureaucracy everywhere has become much slower because there are no incentives to be fast but countless incentives to be slow.
5. Lawsuits. It's easy to say "I'm hurting, I'll take anything". But, then, there are rights you cannot give away. If a drug harms you, you will sue. If it kills you, your family will sue. The whole system is bogged down by lawsuits with massive disproportionate payouts. The early biotech companies and scientists involved often cannot deal with even a mistaken lawsuit.
We need a much more comprehensive overhaul of the system, starting with open access laws to all data pertaining to any drugs that are on the market (no manufacturer can keep anything secret for a drug that people take), an FDA that has much more authority and much less industry capture, medical tort reform, to create a system where in exchange it actually makes sense to provide fast tracked approval.
You're missing the part where the FDA has a revolving door with the biggest pharma companies. To think the FDA is some flawed, but impartial, judge of drugs is the key problem. The FDA is controlled by big pharma. No more, no less.
As other comments have pointed out, I'm not sure why the author can't access experimental therapies. Clinical trials or even compassionate use program (prior to FDA approval) are very common.
When a gov org cares about how it will "look" over wether it kills you - you live under tyranny.
A common example why government doesn't solve problems well. Because it's an absolute governing law, there's nowhere else to turn to. This creates an industry of snake oil that preys upon people both as regulated medicine and homeopathic remedies. In practice vertical integration is a requirement for economies of scale. This means all medicines must be created by singular centralized corporations. These corps buy out the regulatory and now we have an incredibly inefficient and locked out market that prevents innovation.
All orgs should be sunset after 20 years by law. Repeal the FDA, replace it.
The reality of cancer is a bit paralysing to anyone who has had direct exposure to it and there is nothing really overstated about it in the common sense of culture. Everyone’s fight is different, because there are so many paths to take and they keep changing as research advances, but the time available is limited. Besides being restricted, cancer drugs are also notoriously expensive, but for the more self-determined individual there is the option of off-shore pharmacies (many based out of India) and perhaps even Chinese chemical labs (anything on AliBaba must be assumed to be completely unreliable; however, some of the labs which are referenced by scientific papers as suppliers are actually happy to do business after only a little bit of social engineering). Unfortunately this approach is limited to relatively simple pharmacological interventions; anything that requires complex medical procedures (including palliative care) and has to happen in a hospital will require normal legal compliance and the cooperation of a doctor. There are stories of people who have gone far and beyond to enrol into cutting edge clinical trials [1] – usually with the energetic support of a loved one. In those cases, even with the consent of a doctor, the logistics and expenses aren’t trivial. There is much to say in general about the questionable role of institutions who gate-keep access to medical procedures under the pretext of protecting reckless consumers – but it wouldn’t feel right to steer the conversation too much away from cancer.
> This makes it nearly impossible for patients to find an appropriate clinical trial, discouraging all but the most stubborn–people like Mike Hindt, and people like Stephanie Florence. By her own admission, Florence, 44, a photographer living in Lewiston, Idaho, had to “bulldoze” her way into a trial by being persistent to the point of obnoxiousness.
> When she found out she was a candidate for a new trial, she also learned another hard truth: trials don’t come to patients. Patients have to go to the trials.
> In August, she and her husband drove from Raleigh to Boston, despite having no place to stay. After a week in a hotel room paid for by their daughter, they wrote about their circumstances on a community blog. Several people in the area offered the couple rent-free housing during Price’s treatment. In order to pay for food and other expenses, the couple are trying to sell their home, and Price’s husband, laid off from his job at IBM, took a couple of part-time shifts a week at the outdoor-apparel store REI.
Not sure how this intersects with the author's reality. It is sad to see article after article spewing nothing but hatred towards Trump --almost purely from an ideological perspective-- when something like this could help so many.
This, in more ways than one, demonstrates how difficult of a problem this is. When people's lives become game pieces in political battles, the people lose and politicians, well, use them to score points towards their own career objectives.
I read in a comment that the author lives in NY, where, apparently, Right to Try isn't available. If find this interesting when a federal law has been in place since 2018.
This is one of the things that can be perplexing about the US system of government. Here we have a state preventing people from having access to treatments that could materially affect their illness when federal laws allow it.
While I do understand the many advantages of the independence granted to states by the US constitution, sometimes it feels like the US has devolved into a fifty regions pretending to be united as a nation when they are actually not and, as a result, end-up conspiring to damage the very societies they claim to protect.
Education is another example of this. All nations with excellent systems of education (and the results to prove it) have national-level planning, management and standards. In the US, not only is our system of education fragmented at the State level. Our schools are run by fucking unions organized as districts, each with their own axe to grind. It is no surprise the results are what they are.
We somehow manage to extend some of this "excellence" (sarcasm) into every level of healthcare.
According to wikipedia, many types of squamous cell carcinomas are associated with HPV infection. [0]
Another area where the US has lagged which would prevent a lot of these cancers from ever developing in the first place is HPV vaccination. Last I heard it was only females who were being routinely vaccinated, and relatively recently at that. We should really be prioritizing eradication of HPV.
There's a wild book from 2006 called Overdose (by Richard Epstein), that makes a more or less libertarian argument for deregulation of the drug industry. What the book misses is that before the FDA and the Pure Food and Drug Act is that anyone who thought they could make a buck by poisoning as many people as possible did exactly that. And, especially given the "tort reform" prevalent in red states, there is fairly minimal disincentive for corporations to kill people in the US.
There is no 100% correct answer here. As soon as you speed up the process, there are still going to be people that just miss out, and then we will have people saying 4 months is too long, it should take 2 months, or let AI approve it, etc. Desperation skews perspective.
The issue with having a standardized approach to people getting experimental drugs is it opens up its own kind of mini-market unless the implication is they would be required to be free by law. And desperation is not the right mindset to make law or rational decisions.
Not trying to sound heartless, its just not as easy as saying "go faster".
This is my brother. I love you.
Anyone who has suffered through this disease or has a loved one that experienced it knows the feeling of helplessness.
More on Jake’s story below, and a link to the fundraiser to support him and his wife: https://www.gofundme.com/f/help-the-fight-against-cancer-wit...
Be kind and good to your loved ones. Life is short and no one knows how much time we have left. While the FDA’s antiquated bureaucracy does no good, the true enemy is the disease itself. I believe in science and I hope that someday no one else will needlessly suffer as my brother has.
You be good. I love you.
This is the real reminder for young people. Every single one of us is one tiny cellular mishap away from an untreatable, agonizing demise. Be KIND to one another, because when it is your turn to die, you will have wanted to have had a positive impact on the world and those around you.
Stabbing backs to maybe get a pay raise will mean nothing to you or your family. It's just one more person who won't honor your temporary existence.
Be KIND.
Memento mori
The surname is very familiar. I checked and Jake is in fact a long-standing member of this community as jseliger [1].
I’m sorry for the very difficult times your brother is going through. I hope and pray that his situation improves.
1: https://news.ycombinator.com/user?id=jseliger
more specifically, this topic has been brought here https://news.ycombinator.com/item?id=36393383
I was a student of your brother's at the University of Arizona for a semester. It was over a decade ago at this point, but I think it was English 109. It's hard to explain how humbling it felt to chat with him one-on-one. He struck me as a genuine, intelligent, and friendly guy who was worth listening to.
This is such terrible news and I wish Jake and yourself the best.
What a genuine, intelligent, and friendly way to have remembered such a fella worth listening to.
>We get wise too late
>and old too soon.
>—Danish proverb
If possible put your email, even a throwaway, in your profile, and I will send a message.
3 replies →
Thank you for the kind note. I’m sure he’d love to hear from you.
"We need to have a much stronger “right to try” presumption"
Quite.
I'm now four years older than my mother was when she passed away after two really exciting years. I can't remember the exact description of the killer but "squamous" was involved. Radio, chemo, surgery bordering on butchery etc. Bout one seemed to be in remission and all clear sounded only to be rescinded a few months later, second run was a negative outcome. Faith healer for a laugh "but you never know" - mum wasn't daft but when you are out of reasonable options, you might as well invent a few more!
However, there is still hope whilst breathe still flows and there is absolutely nothing wrong with hoping for a miracle. They do sometimes happen. Keep fighting and kicking and being a pain and only give up when it is obviously hopeless.
Love you too. Take care.
Lost my brother to a carcinoma, a disease that most likely will be successfully treated, cured and even prevented in my lifetime. I feel for your brother but also for you.
Sorry for your loss. I hope you’ve found some peace.
While I can't comment on this particular case, I sincerely recommend Americans to explore treatment options for treatable diseases in other countries - like India, South Korea, Cuba (?) etc. - that have excellent doctors and decent healthcare infrastructure. They may charge foreigners a bit more than the locals, but you will get better service that is unlikely to bankrupt you.
(Not sure about Cuba's current healthcare infrastructure).
Thank you and love you too.
I would hate to ask the author this, as it seems cruel, but is the FDA denying him access? As he points out, Moderna has two drug trials going. The FDA "right to try" page[0] clearly spells out that Moderna could give him unproven medicine currently in a clinical trial under the right to try laws. So Moderna could let him into one of the two studies, or give him the medicine under the right to try laws if it rejects him.
Likely, Moderna doesn't want him to take the drugs because they will probably be ineffective this late in the cancer stage. It doesn't want its treatment to be associated with his death.
[0]https://www.fda.gov/patients/learn-about-expanded-access-and...
Actually the Moderna trials are recruiting metastatic and treatment resistant disease. From his description he has not met inclusion/exclusion criteria for the studies due to treatments received and not received rather than being too advanced in stage.
It's highly highly highly unusual to be offering an experimental therapy on compassionate grounds when conventional options that have potential to actually work well haven't been tried yet. In this post he only describes locoregional therapy and it appears he has not tried anything systemic yet.
The closest I've seen is we at least try a very short attempt of something in clinical use and then say patient refused/intolerable side-effects/treatment failure and move on. I can't imagine a circumstance where medical ethics would allow to skip a trial of validated therapy for something without even phase I data. It's not like this mRNA by Moderna is known to actually work.
Are there conventional therapies that he has not tried that could be effective? It seems he has never had chemotherapy, but he implies at this point that's a long, almost impossible, shot.
5 replies →
Do our “right to try” laws mean: only after you’ve gone through our $5m treatment plans?
1 reply →
[flagged]
I believe the oncologist has to present the case to Moderna for use. If insurance is involved, insurance will deny it.
Fairly certain that someone who has exhausted all supported treatment options doesn't care about insurance anymore.
I think the issue is that Moderna just doesn’t have much incentive to do it and it’s more a distraction than anything. But yeah it could also just be too late. My dad was recently in a similar position, but by the time he theoretically could get his hands on the drug, he was too weak too handle them.
I feel somewhat closer to this person because I was once in his position as a child fighting a neuroblastoma in 1981 and some how my mother found a way to get me on an experimental list which saved my life. Half of the kids that took the drug died by the time they were teens due to heart failure, obviously I wasn't one of them, but am thankful for the chance to live a full life.
When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning. That's something our government has forgotten about or doesn't care about. If I was in this persons shoes, I would make it as personal as possible against those in control of the FDA. Show up at their houses, work, kids soccer practice, get in their face and let them see what their inaction is doing in person.
> When the odds are against survival, there shouldn't be any rules limiting treatment, if it means even a slightly higher chance of winning.
I agree with you. But the FDA would ask you to rigorously define "slightly higher chance of winning" -- and prove it. In the event you cannot do this, they believe that letting you try an experimental drug would be more unethical than letting you die of neglect.
So I'd rephrase that statement of yours: "When the odds are against survival, there shouldn't be any rules limiting treatment, regardless of type of treatment or odds of efficacy." ("When the odds are against survival" can be quantified, e.g. a 90% chance of dying within a year.)
I am not yet done thinking on this area, so my thoughts here are incomplete, but thay said:
Would this not also open the door for any snakeoil salesman to prey on what might be medically "hopeless" cases?
If I am ever diagnosed with something currently uncurable, but there are experimental stuff in the works, of course I'd like a shot at those experimental drugs, but I hope that me/my family would also not squander whatever assets we have on snakeoil, in which case I'd rather my surviving family was not impoverished in the fight.
I assume that, at least partially, this is why regulations in this area were put in place to begin with.
2 replies →
Before anyone shows up at FDA decision makers' kids soccer practice please consider things from the point of view of an FDA decision maker. They have to make a choice which they know will lead to both type 1 and type 2 errors. For life saving medicine, when the decision isn't clear, both type 1 and type 2 errors are awful. It's likely they already feel the burden of responsibility.
Why don't we just have a schedule/tier system?
Category A - approved by the FDA, basically what we have right now
Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Category E - experimental and basically limited run from pharmaceutical companies. These essentially need to be tailor-made or produced by a GMP kilo lab. There are plenty of drugs in this category - I worked on them - and the intended recipients are entirely animals, QA, and regulatory agencies. But maybe if some crazy S.R. Hadden type (billionaire in Contact) wants to guinea pig themselves, let em.
The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
> Category B - approved by some other established regulatory body (EU). Comes with all the warnings, doctors can write it off-label, insurance companies may not cover it but doctors can ask for a variance
We can already prescribe off-label if the FDA has approved it for at least 1 indication, and it mostly gets reimbursed.
> Category C - approved by some non-OECD body. Insurance companies under no obligation to cover
There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly. The US is the largest market for manufacturers so they almost always start here.
> Category D - experimental, this is stuff maybe still only in animal models, but pharmacies can still order and dispense it
Pharmacists and physicians are ethically bound to prescribe to the best of their ability and avoid harm, by prescribing something only validated in animal models it means we are not prescribing/dispensing something validated in humans and therefore not meeting or exceeding the standard of care.
This sounds like a recipe for killing people.
> The latter category also opens the door for custom therapies (gene/mRNA) that you basically can't test the active pharmaceutical ingredient for efficacy on.
Huh? There are many ongoing gene-directed and mRNA studies being tested.
> This sounds like a recipe for killing people.
Do you know what else sounds like a recipe for killing people? Not allowing people to access therapeutics that might save their life because it hasn't yet gone through regulatory approval yet for whatever reason (delays, too expensive to submit), etc.
> There's very little that's approved by a non-US body and approved by the EU or non-OECD body that warrants clinical use, and if it is it gets reviewed quickly
LOL. What are you talking about. There are so many examples.
One of the most tragic is amisulpride. Amisulpride is an antipsychotic medication used to treat schizophrenia and other psychiatric conditions. Some key notes about its regulatory status:
- Amisulpride was first approved in France in the 1980s and is widely used in Europe.
- It was never approved by the FDA for use in the United States, and at this point there's not organization that can afford to go through the approval process because there's no patent.
- The reason often cited is that the manufacturer did not apply for approval with the FDA. It was likely not considered commercially viable for the US market at the time.
- Amisulpride is believed to have comparable efficacy to other second-generation antipsychotics like olanzapine and risperidone, but with a lower side effect burden according to some studies.
- In Europe, amisulpride is considered a first-line treatment option for schizophrenia, but American psychiatrists do not have access to it. According to some sources, it is literally recommended as the best antipsychotic in other countries.
6 replies →
This are already dead people walking.
There are "right to try" laws both Federally and in 40+ states. It's unfortunate the author doesn't address those, I'm curious how they interact with his case.
It appears that he is in New York, which doesn’t have a right to try law on the books.
If that is the reason, perhaps temporarily moving to another state might help? The author appears to still be mobile.
1 reply →
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.
One aspect of the problem here is the difficulty in running a clinical trial, particularly at the recruitment stage. The covid-19 trials all had a surfeit of participants because of a pandemic, but with modern cancer treatment trials the qualification requirements significantly cut down on the eligible population.
This, in itself, isn't a huge obstacle. The problem is the state of healthcare data systems. It's next to impossible to perform high-quality search (even by individuals approved to do so by the IRB). The state of the art in most places is regex searching in SQL.
This is something we have the power to contribute to. Bringing modern search capabilities to important datasets like health (while maintaining HIPAA-conpliance) is a much better use of engineering time than mining spyware data for creepy insights...
[Disclosure: I contributed heavily to one of the major medical search products on the market. We dealt with organisations that expended tens of thousands of dollars and many months per candidate for recruitment. Using some very straightforward IR tech we literally found all their candidates in a few minutes, plus many more. But there is so much more to do!]
Yes, very true. Beyond just access to clinical data there are often major differences between how the same conditions are recorded between different provider organizations based on EHR data models and local practices. Researchers who want to use data from multiple organizations typically have to put a huge amount of work into their data pipelines for cleansing and normalization. Some standards development organizations such as HL7 (including their various FHIR accelerators) are now writing more detailed and specific implementation guides to improve data quality and consistency so I would encourage technologists to contribute to those projects.
Read the rest of his blog; it’s wonderful and I’m devastated that someone I followed for years is going to vanish.
Thank you for giving us all some of your time on this earth.
I wonder - both in this specific case, and in general - if anyone here on HN has enough media/political reach to spread this message.
This case reminds me a lot of the FAA realizing that safety restrictions for toddlers would increase deaths as more people would drive. (https://www.ntsb.gov/news/events/Documents/child_safety-Clau..., https://www.ucsf.edu/news/2003/10/97119/airline-infant-safet...)
There seems to be a growing sentiment that FDA delenda est, but if we don't fix the underlying problem that led to this situation, it will just come back.
As the author says, no one ever blames the FDA for the people it failed to save. But approve something without the certainty that it isn't potentially going to kill someone, and there will be hell to your doorstep.
Even if you want the experimental treatment, you cannot get it. Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault. This is sometimes also known as the Copenhagen interpretation of Ethics.
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 options want those too, because nobody wants to go through chemotherapy or whatever.
Medical authorities have a shitty job.
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.
43 replies →
> 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.
8 replies →
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.
4 replies →
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.
9 replies →
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.
14 replies →
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.
For those who are curious, the term was coined on this blog post[1]:
> The Copenhagen Interpretation of quantum mechanics says that you can have a particle spinning clockwise and counterclockwise at the same time – until you look at it, at which point it definitely becomes one or the other. The theory claims that observing reality fundamentally changes it.
> The Copenhagen Interpretation of Ethics says that when you observe or interact with a problem in any way, you can be blamed for it. At the very least, you are to blame for not doing more. Even if you don’t make the problem worse, even if you make it slightly better, the ethical burden of the problem falls on you as soon as you observe it. In particular, if you interact with a problem and benefit from it, you are a complete monster. I don’t subscribe to this school of thought, but it seems pretty popular.
The post provides real life examples of government programs, nonprofits, and individuals being criticized for helping in the “wrong” way.
1. https://web.archive.org/web/20210125231725/https://blog.jaib...
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?
2 replies →
So, you would flip the railroad switch to kill only 1 instead of 5 helpless people?
5 replies →
This has been a common complaint for decades. We always want to try rush experimental drugs/procedures that “show promise”.
How often do these drugs, etc turn out to effective? 25 years ago we wanted to rush gene therapy and that didn’t turn out well. Someone died. It probably set back gene therapy:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/
I think the solution is to invest more into medical research now, then when we, or someone we know, eventually ends up with some horrible disease, (cancer(s), Alzheimer’s, Parkinson’s, etc) 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 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.
7 replies →
> 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.
8 replies →
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.
17 replies →
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.
5 replies →
> Even if you want the experimental treatment, you cannot get it.
Says who? In terminal truly no-option diseases (e.g. glioblastoma multiforme) it’s pretty easy to get access to experimental therapies on compassionate grounds.
The challenge in this particular case brings us to:
> Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault.
This is a false dichotomy. What’s unethical is offering experimental therapy with ?? effect when there are evidence based palliative treatments (e.g. conventional chemotherapy) with proven overall survival benefit.
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.
No one is advocating or suggesting we just let people die.
>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.
3 replies →
There's this overabundance of the need for safety that's overcome society.
It's as if we can't assess tradeoffs anymore.
You see it with the lack of children playing outside - even though random kidnappings are almost a nil risk and that they're more likely to get by a car.
Defective toys. Defective carseats. Millions get recalled for a failed few.
You saw it with masks. You see it with speech, "words are violence".
Everyone wanting the illusion of feeling completely safe.
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.
One issue is, who pays for it?
Experimental treatments often are very expensive, I believe require a lot of study of the patient and so on ...
It's not like a magical pill(s) you take an go home and live or don't and everyone says "well he consented so he took his chances". The entire process of experimental treatments is hugely expensive.
> Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault.
If a train is coming with someone pinned to the tracks, and they are begging you to hand them an axe so they can remove their own leg-- knowing they may die from blood loss, do you just do nothing?
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?
It's a high worth debate, maybe there's a ethics curve.. for most cases you have the normal "don't do harm" but for life threatening you need another board to remove some stops without letting the scams proliferate.
"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.
1 reply →
> Even if you want the experimental treatment, you cannot get it.
fortunately, Baja California seems to have everything. Or specifically, a different drug approval strategy that is right in the middle of this.
The FDA's main limitation is that it gives a one to one relationship in approvals. A substance is seemingly evaluated for a single narrow ailment. While evaluation process is a threshold of side effects as well as efficacy in treating that single narrow ailment. This process could be expanded to recognize that fulfilling the side effect issue could expand its use in other ways, more easily than whatever semantical distinction of easier the FDA uses now. There could be more possibilities for one to many approvals.
Off label prescriptions are legal and very common.
1 reply →
Going on a tangent here: there's a reason medicine is heavily regulated—because of the lessons we've learned the hard way. The same reason law is also heavily regulated. Some of these lessons have become obscured by time, unfortunately. Other lessons may not be fully applicable to the modern state of the field. (I say this as a qualified doctor and lawyer with some appreciation of the history of both fields.)
Are the current regulation regimes perfect? No. Would we be better off without it? I doubt it. Should we try to strike a balance between regulation and innovation? Yes—but doing so is devilishly tricky. No matter what you do, someone somewhere will be unhappy.
> Even if you want the experimental treatment, you cannot get it. Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault. This is sometimes also known as the Copenhagen interpretation of Ethics.
Most people (myself included) would not agree to that. Experimental treatment should be made possible - at least if there have been promising results with previous studies (animals, small trials etc.). There must be a safeguard, however, to make it impossible to sell false hope to dying people - because they will pay for everything, even if it does more harm than good.
I think it could be ethical to let people try experimental treatments in the context of a phase 1 clinical trial, ensuring that something is learned from the attempt. However, I have also heard that an issue with that constraint is that connecting patients to clinical trials is a huge logistical problem that has not been well-solved.
It actually seems like the kind of problem that could be a good fit for tech: have a registry of clinical trials, make sure it’s widely known and consistently used. I don’t know much about the problem, though, so I don’t know if or whether that’s unrealistic.
> Even if you want the experimental treatment, you cannot get it. Killing someone in an attempt to help is deeply unethical, while merely letting them die is not your fault. This is sometimes also known as the Copenhagen interpretation of Ethics.
Interesting. Thanks for sharing the "Copenhagen interpretation of Ethics". I've thought many times about this problem, didn't know it had a name.
Comes to mind Dante Alighieri: "The hottest places in Hell are reserved for those who, in a period of moral crisis, maintain their neutrality."
I still think they need another category than what they have now.
My understanding of the current categories of drugs are you have "banned" and "has this specific therapeutic effect that costs billions of dollars to prove".
A category of "this doesn't kill you" in the middle would probably alleviate most of this. Insurance only has to pay for things with proven therapeutic effects, but you can shield people from poison and get a lot more data way cheaper by having his middle category.
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.
1 reply →
I think what really drives me crazy is that the FDA approval can limit me taking something.
Put simply, If you believe “my body, my choice” then the current regulatory system is pretty messed up.
To be clear, I’m fine with the FDA existing as a labeling body. Sure label something FDA approved. But don’t limit what we can take because it’s not approved.
Otherwise, you end up with cases like this and many others, where an industry can easily be regulatory captured and ensure competitors are slow or unable to enter the market.
I call it Pontius Pilate's Ethics.
It is (a very rational) approach for administrative workers, who get little credit for getting things better, but are at risk when they can be taken accountable for something terrible.
That way, for example, in Germany, there was a halt on the Astra-Zeneca vaccine after a few cases of thrombosis per million. For comparison, it is one in six for COVID. The halt, most likely, caused many deaths. Yet, these deaths "have happened". If there were a death because an administrative organ didn't take action - the organ would be considered responsible.
For the matter, Pontius Pilate was an administrative worker. And his incentives were aligned accordingly.
In the language of the Trolley Problem, it is doing nothing (no matter how many are there on the tracks) or (even better) finding a way to pass the lever to someone else.
Sam Peltzman goes into this and the statistics in his book Regulation of Pharmaceutical Innovation:
https://www.amazon.com/Regulation-Pharmaceutical-Innovation-...
Is there really a growing sentiment?
If you have a system without problems, I’d be more worried.
Edge cases like OP’s can’t be solved by any system. All systems have problems with things falling through the cracks.
That’s why lobbying exists. So people like OP can bring attention to a specific problem and lobby for it.
Taking about changing the system is missing the point.
The FDA could create a standard consent form for nonapproved treatment that patients and doctors would sign, which would indemnify the physician from legal repercussions, but they don't, and they bear full blame for that. The AMA would still have its own regulations about the limits of ethical experimentation, with the revocation of a medical license as punishment to serious offenders, and malpractice safeguards could still be there. State laws about gross medical negligence are also an option.
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.
4 replies →
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.
Imo the whole US medical complex needs competition from a small but sophisticated libertarian state without any of the regulations that formed the present system, and I think it will happen. The market demands it, and the world would be better off with some competition. Most likely it will begin with some small nation that sells anti-aging therapies.
There are companies from which you can order bespoke mRNAs. Lead times vary but are in the weeks. Many are abroad. The other components of mRNA vaccines can be assembled by someone with 2 years of biochemical Ph.D. experience. There are no laws against a person assembling and injecting themselves with anything.
I have extra sympathy for the writer of this article, since mRNA vaccines (even if they were a random sequence) are relatively lower risk than many other sorts cancer interventions which are FDA approved. I happen to be an ex-professor, who is a director at a drug company. I know that if I were the unfortunate author of this article, whose heart is in the right place. I would probably be injecting myself with my own janky version of whatever offered hope.
Whether that would actually change my prognosis? Probably not. I can say though that I _would_ and I believe others are entitled to positive freedoms I'd afford myself.
The author seems to forget that entering a trial doesn't necessarily give you access to the treatment. You have as many chances to be in the control group receiving a placebo.
And as bad, sad and frustrating as it sounds to someone in a desperate situation, it is for the greater good of many more human beings, protecting us from snake oil.
Right now he has a 0% chance of survival. If the experimental treatment is at all effective, the probability of not being in the control group multiplied by the probability of effective treatment is greater than 0%.
The probability of a more painful death is also greater than 0%. So it the probability that something could go wrong and cause publicity which would interfere with the testing or approval of the drug and affect other people's access in the future*. There are always tradeoffs.
*this person takes the drug. Two days later they die of a heart attack. Was it caused by the drug? How many resources should be spent to determine that? Should that death be listed in the potential side effects? What if the news story publishes an article and scares people off from the trial? What if it's later proven that the drug had no effect on the heart attack but the distraction from it delayed 10,000 people's access to the drug?
The world is complicated.
1 reply →
> The author seems to forget that entering a trial doesn't necessarily give you access to the treatment. You have as many chances to be in the control group receiving a placebo.
This is untrue, in this case.
Typically, only some phase 2 and phase 3 trials are randomised; the treatments that the author refers to are at an earlier stage of development and so not in either of these phases. All patients will receive the active therapy.
It's also worth noting that for cancer trials, while new treatments in these later phases may be tested against a placebo, it's never just a placebo - that would be unethical. If the new treatment is an add-on to an existing standard-of-care treatment, then they'll receive the standard-of-care treatment in the placebo group. If it's not an add-on, then it will be tested directly against the standard-of-care. If there isn't an established SoC, it can sometimes be approved without a randomised trial, if the results are good enough.
To note, the placebo group is typically getting the best current existing treatment. Rather than nothing. Although in some cases the best treatment is still nothing, which sucks.
It is against medical ethics for the placebo not to be the current standard of care, and experimentally it must be… If you can’t beat the current standard of care then your drug isn’t effective.
The greater good argument is repugnant in this case. He is going to die, and deserves an opportunity to do whatever is possible to save himself, including new and little-tested, and likely ineffective treatments. He literally had nothings to lose.
And in this case he would be actively helping humanity as well by being a test case. We would all gain knowledges and information from his treatment, if he could get it.
This policy hurts all of us.
In serious (esp. life-threatening) situations, the placebo is, or is supplemented with, the normal course of medicine, not sugar water.
Butnot habing access to normal course of medicine is not what the author is complaining about
There's a very easy regulatory solution: Roll the drug approval process back to the way things were done prior to 1962. Back then, safety testing was all that was required. Efficacy testing -- which is difficult, expensive, arguably unethical in itself, and in some cases effectively impossible -- was not required. Drugs cost ~20-50x less to bring to market, and were brought to market faster. Indeed the 40s and 50s are still known as the pharmaceutical industry's "Golden Age." And it wasn't only because of low-hanging fruit.
Pair this paradigm with extensive postmarketing surveillance and periodic reviews for efficacy in a patient population. These could be done at two years, five years, and eight years -- and approval automatically rescinded if safety issues arise or efficacy is close to null.
Give people with fatal diseases a "right to try" drugs that haven't passed safety testing -- and use that data.
Ban drug advertising in public-facing media.
Simple as.
I remember Softenon.
> it wasn't only because of low-hanging fruit.
Yeah, right. They had such advanced cancer medication back then.
> Give people with fatal diseases a "right to try" drugs that haven't passed safety testing -- and use that data.
That data is practically worthless.
I'm in favor of having people try out medication, but it will need to be heavily regulated. And we know what happens to regulation: a party comes along that doesn't like regulation, or gets bribed, and the regulation goes out the window. It's a good way to start another opium crisis.
> "B-but Thalidomide!"
This is the reflexive response to every common-sense proposal to roll back the regulatory burden.
I'd raise a couple of points in response:
First, Thalidomide was never approved in the USA -- for safety reasons. The mechanisms that were in place at the time did their job.
Second, the response to Thalidomide was overblown and indeed downright hysterical. "Better to let 100,000 people die of neglect than allow one person to suffer an awful drug reaction" is not rational policy.
> That data is practically worthless.
Enough "practically" worthless data, and you get somewhere. It's a matter of quantity. Obtaining "hiqh quality" data is often unethical in medical practice.
2 replies →
My brother had an excellent metaphor:
> Say you're a runner. In the beginning of your competitive career, you get the most gains by becoming a better runner. And then at some point, you get more gains by shooting (or bribing) the ref.
The world "simple" is doing so much heavy lifting here, it might as well be written as ______ instead.
I’m fine with that as long as insurance does not pay for any drugs without efficacy testing. Also no advertising of any sort.
generally, insurance companies do require efficacy. many of them have decided not to cover aducanumab for that very reason. though this also gives insurance an additional excuse to deny stratospherically-expensive gene therapies and other life-saving new treatments, since even the most effective new drugs won't have e.g. 10 year survival rates until they're a decade old.
agreed on advertising though.
insurance already gets away with not paying for some highly efficacious drugs, so I don't think this will be a problem
I do think that people should have options, especially when there aren't effective treatments, but it's not exactly simple. In most cases, any treatment you pick has the opportunity cost of other treatments, and for life threatening diseases that opportunity cost might be living. Very few, if any, patients are going to be in a position where they can legitimately evaluate the effectiveness of treatments. In most cases, I don't expect health care providers will be in the position to do that either- even most specialists will be treating a wide variety of conditions, and may have relatively little experience with unusual diseases. Even in the best case, this is assuming that drug companies would actually try to make effective drugs rather than looking for other avenues to sell ineffective drugs (or drugs that were only accidentally effective)- I don't that in today's environment that's at all a reasonable assumption. Ultimately, the information asymmetry is vastly weighted in favor of the drug companies, and the cost is lives.
Apparently there is already a Right to Try:
https://www.fda.gov/patients/learn-about-expanded-access-and...
Get rid of prescription requirement too - who needs to see a doc for extra $500 when I can go and pick my own med, and possibly better one.
That's how it works in Mexico. You only need prescription for antibiotics (makes sense as their abuse would create a public problem) and psychologic related drugs (I dont agree with some of them like amitriptyline... ) .
But other than that you can get almost anything even buying it online and get it at home in the next 3 hours.
That's how I buy duloxetine every month.
It's far from a full solution, but it'd be progress.
Ah yes, let’s go back to the days of Thalidomide.
For those that don’t know, the 1962 change is the Kefauver–Harris Amendment, which was a response to one of, if not the, largest overall global crisis of conscience in the medical field. From Wikipedia: “When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness.” After some time it became increasing obvious that while it worked, it caused birth defects in pregnant or soon to be pregnant women, with its manufacturers actively trying to quash the information about such cases; again, from Wikipedia: “Use of thalidomide in pregnancy can cause fetal abnormalities such as phocomelia (malformation of the limbs). In males who are taking the medication, contraception is essential if a partner could become pregnant.”
Thalidomide disfigurements were disturbing. Children born with these disfigurements were not linked to Thalidomide until much later. Thalidomide was in fact not allowed a safety regulation by the FDA initially. It wasn’t until the company producing it, Grünenthal, pressured the FDA. You see, the FDA reviewer for the medication was leery about it after some reports had floated over her desk about a possible remote risk that this could potentially cause birth defects. Grünenthal’s international licensee to the US refused to explain multiple papers that linked Thalidomide usage in pregnant women to birth defects.
As it turns out, not only had Grünenthal known about the issue they had actively worked to silence the information, a ploy that worked until a major change in leadership in Germany.
It was denied usage in East Germany.
For a longer documentary on the subject and how it changed medical safety testing, Plainly Difficult has a very good video on it: https://youtu.be/Vi03zz6eCik
(Note: I am explicitly ignoring the context that the Thalidomide development program was run by an actual Nazi who was responsible for unethical and frankly awful experience on unwilling human subjects in concentration camps. If anything, it only amplifies his concern to hide adverse effects, which he did quite successfully until the company was given what can only be considered “A slap in the face”.)
None of that has anything to do with the proposal you're replying to, which is about the efficacy requirement, not safety.
Everything you said has absolutely nothing to do with what GP said.
Hopefully he makes it into a clinical trial. In case anyone is interested in reading what trial options are available for this type of cancer you can find the trials here: https://www.clinicaltrials.gov/search?cond=Squamous%20Cell%2...
There are 469 studies for that type of cancer that are accepting males of his age, of which 260 are in the US, on that site. Obviously, many are going to be inappropriate, but hopefully with something is available to him.
What I don't understand is why the FDA doesn't automatically rubber stamp approvals on medicine approved in Canada and the European Union. We all know their medicine is good - so why can't I get it?!
Money and politics. Why can someone drive for 6 months in a country with a foreign driver's license but can't get a local license?
I've had this misdiagnosed medical condition for 25 years by multiple doctors. Nothing serious but extremely annoying. There are approved drugs in Europe for decades which are much better than the ones approved in North America. One day the company making the drug that's approved in North America decided to stop making it! You just could not get it. This was the event that finally led to the correct diagnosis for my condition because I was in so much pain I got to see the expert. Turns out my condition has a very simple non-prescription solution and for 25 years I've been taking the wrong meds that happen to alleviate this different condition as well!
So I am good but this condition is not uncommon. What are all the other people that really need this drug in North America doing?
I'm not sure what's the takeaway here. Maybe that efficient/smart organizations generally don't exist. This is just a reflection of human nature.
If you're okay with it, could you expand/name the condition you thought you had, the actual one, and the medication(s)? Never know, might help someone else out
1 reply →
Why can someone drive for 6 months in a country with a foreign driver's license but can't get a local license?
A government issued id, like a driver's license, is often required for various services like opening bank account, a telephone connection, avail some government service etc. Thus a local driver's license can be used for deception by a foreigner who wants to pretend to be a local citizen.
1 reply →
Because it then becomes a kind of race to the bottom, where all manufacturers will approve medecine in the easiest country, a bit like flag on convenience for ships
They already do that. Having approval and data in another country makes it much easier to get FDA approval. But it's still a lengthy process, costs a lot of money, and often puts you in competition with other options that are approved. There are drugs that have been used for decades in Europe, are perfectly safe and proven to be more effective, and are not available in the USA (and likely the other way around, I'm just aware of specific examples there).
Sounds great, where do I sign up?
Thalidomide was widely approved, and I'm glad the FDA didn't rubber stamp it.
But that’s the problem. No regulatory body has perfect judgement, so they’ll all approve some harmful things and ban some helpful things. If you’re so strict that you don’t allow thalidomide, you’ll also ban stuff like beta blockers for an extra decade, causing 80,000 deaths. The argument in favor of loosening restrictions is that it would reduce overall death and suffering.
20 replies →
Sure, but they did rubber stamp Fen-phen and Vioxx despite plenty of people within the FDA understanding it should come with a black box warning. The FDA needs a win that's more recent than 1971 if they want to demonstrate their efficacy as regulators.
I take a derivative, Lenalidomide, for cancer maintenance. I am very glad the FDA approved it.
The FDA can approve a new drug in under a year as we saw with covid vaccines. Every time an effective drug is made and they don't people die waiting.
5 replies →
I guess we know that, but why doesn't the EU rubber stamp medicine that's approved in the US? In my opinion it's actually good for there to be independent bodies reviewing things.
We all know why the EU doesn't rubber stamp US medicine...
There are many divergent if not contradictory regulatory findings levels and limits between the US Canada and Europe. eg. Tolerable total cholesterol levels US:200 Euro: 240 (last I checked, these move around quite a bit. In the 70s the US banned Cyclamates as an artificial sweetener, but approved Sacharine while Canada approved Cyclamates and banned Sacharin. For Glaucoma treatment Europe is "Laser first, drugs second" while the US is Drugs first, laser surgery second. etc etc.
Somewhat famously the US not doing this stopped Thalidomide being such a large issue in the US, but of course one example of it failing doesn't mean it is inherently bad policy.
It’s strange how people trot that out and never discuss the inverse.
So all drugs will always be trialed at the most lax country and get approved at a stricter one? Then why make rules because the laxest country will be the one used and in control of approvals
Because they might make mistakes? See: thalidomide
> USA rubber stamps probably safe food items. Europe goes WTF how dare they think its safe.
> USA refuses to accept rubber stamp European experimental medication. Europe pikachu face
This quote sounds like self interest in the article, but there is more to it:
> If anything goes wrong,” he argued, “think how bad it will look that we approved the drug so quickly“
People who take an approved drug are relying on the result and authority of a scientific process — across all drugs. Some scary results and people may start to fear the process, which may end up killing more people.
That said I’m sympathetic to his plight and think that he sounds like a candidate for the compassionate use program. Any result would not help approval as who in such a program would volunteer to be randomized into a placebo arm? They’d just plead in a prior human administration disclosure section of any NDA.
(Also, pragmatically, immunotherapy grate nets are customized and extremely expensive. Who will underwrite it? Not the drug company who would have nothing to gain, not the insurance company, and I doubt the patient could afford it).
It’s a sad story all around.
Parts of this problem are part of what a company a friend of mine works for is trying to solve:
https://xcures.com/
Part of what they do is they match patients with clinical trials for whom they would be candidates and then facilitate the process on an on-going basis. Apparently this bypasses a number of bureaucratic hurdles which can be faced by patients; for example a patient receiving care from a particular research institution might not be informed about trials being conducted by other, non-affiliated institutions.
Naturally, there's rather more than this to them, but this part sticks out in my mind.
And finally, take what I'm saying with a bit of a grain of salt because I am remembering from casual dinner-time discussions that I had some time ago with my friend. My memory might be bad, they may have changed what they do since I last talked with my friend about it, etc.
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 died in 2021 and I find it difficult to think metformin may have helped him live a more comfortable life. I know it's not a cure but the research seems to indicate a significant improvement for anyone with IPF taking metformin along with anti-fibrotic medications which Dad did take. We should have just used Mom's metformin really Dad had nothing to lose but it's hard to see that at the time.
When I read the original story and this metformin one, I'm so glad I live in a country where I basically can walk to a pharmacy and by most drugs without a prescription.
I can buy 60 slow release 500mg tablets online for about $10 usd and they'll send them to my home for about 1 extra dollar.
Fuck the government, fuck their controls. If I or someone I love is dying, I'll make sure to try ANY and all options, even if it has a slight chance of working. Everyone has a right to fight for their live.
[1]https://www.fahorro.com/metformina-500-mg-liberacion-prolong...
>My Dad's doctor wouldn't even discuss it and dismissed it outright.
Given metformins safety and cost profile, your dads doctor sucked. They should put it in the water of the 60+ crowd.
Anecdotal. When "quack" * science helped.
After COVID (both the disease and the vaxx), I got heart arrhythmia, I had around 5000 irregular heart beats a day (PVCs and PACs mainly), and those all happen in a matter of hours, so when they happen, it's pretty debilitating.
After a while, I invested in a Bluetooth stethoscope and ECG watches, the doctors finally believed I have something. However, the cardiologist's advice was to learn to live with it, because it's completely harmless and in young people, ablation, beta blockers are not worth the risk.
Having these irregular heart beats is a very uncomfortable feeling, so I was looking for articles about the root causes and potential treatments.
After trying a couple of things (both pills and lifestyle changes), I found an article that says arginine and taurine reduced the number of irregular heart beats in their experiment. I tried it out and I have basically 20-50 irregular heart beats a day. When I stop taking them, the irregular heart beats come back.
Now, I know I'm doing something that is potentially risky, but to me it is worth it (and I reduced my dosage, and I try to quit using them every couple of months).
* it's not really quack science as the science is real, just that me applying it in my situation was not recommended by a doctor
I had a similar presentation: sudden 1-3% PAC load at rest following an asymptomatic COVID infection. Cardiac MRI showed minor residual scar tissue. I noticed my diet was pretty seriously deficient in magnesium, and after starting a supplement the abnormal beats have nearly vanished.
1 reply →
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.
I read this, and while I felt immense sadness, I will obviously move on with my life soon enough and forget about it. I wondered, if I were ever in the same situation, and someone read what I wrote before dying, they might empathize for a bit, but then they'd move on as well.
I just really wish that there's something beyond death, that there's something out there, and that all the suffering and unfairness and randomness in life is not for nothing. I hope we someday truly figure out what the fuck we are doing here in this universe. And if not that, at least we reach a point in biology where we have the ability to solve a lot of problems of the mind and body and make life better for everyone.
When there is nothing beyond death, there is no death. We won’t be sitting on the sidelines blindfolded. We won’t exist. From our perspective the death never actually happens.
I’m surprisingly okay with my lack of experience of the billions of years before the earth existed, and I won’t experience the billions after.
That said, just because we can’t stay at Disneyland forever, we might as well go on the rides while we are here.
We are all dying. Some sooner than others. As a student of philosophy, this perspective has driven me to avoid the common status concerns that many people chase.
All though you're correct it is rational to not fear death. I personally, and likely many other people here, have a very very strong aversion to it.
I DO NOT want the cessation of experience.
Ideally, I'd like to continue in perpetuity, to see the sun rise from Venus, or visit my tenth generation offspring on Saturn.
All of those missed experiences would be deeply saddening. To see our species conquer to universe, to see intelligent life bloom in the darkness of space, that is the goal.
3 replies →
I'm not overly concerned about death on its own (I feel it's going to be kind of like being asleep), neither am I that concerned about my role in the universe. Instead, I feel more for people who truly suffer in life maybe due to poverty, or due to disease, etc. who don't get to go on Disneyland rides. It makes me feel what was the point of it all? It has to be teaching us a lesson beyond the "simulation" and if not -- that's what makes me sad -- not my personal fear of death, or anything to do with status.
And even to a lesser extent -- why do we suffer -- is it a law of physics that can't be bent? I don't agree with people who believe more pleasure equals more pain. There will be people who live amazing lives, and those who don't. And so I feel that we as intelligent beings can reduce randomness, and take control of our environment and make sure we can all go on Disneyland rides at least to some extent, and hopefully eventually figure out what's outside of Disneyland.
1 reply →
I'm not scared of death. I'm scared of an extended painful exit.
Let us say that there is nothing beyond death, does that really mean that life is ultimately pointless? I'd argue that the idea that there is nothing beyond death is what makes life all the more meaningful. We are only going to get one shot at all of this, we better make it count.
From this I derive the motivation to work hard at what I do and ultimately try to contribute to the problems we face as a species before I pass. It also makes me appreciate the raw human connection that we can all experience: love, passion, friendship.
I may not be the one to light the altar of discovery that allows us to say, cure cancer or become a spacefaring species, but I will proudly carry the torch and pass it on.
You can philosophise yourself into just about any position: death is real & life is meaningless, death is real and life is meaningful, death is but a transition & this life is meaningless, death is merely an illusion and life is meaningful,
I believe that Jesus is Lord, and everyone who seeks him finds him.
Matthew 7:17 - "Ask and it will be given to you; seek and you will find; knock and the door will be opened to you."
I was given a very clear sign 17 years ago, not when I asked God to prove himself, but only incidentally when I was seeking his guidance on something; it's nevertheless lasted as an undeniable proof for me. Though, it's better to believe without seeing.
John 20:29 - "...blessed are those who have not seen and yet have believed."
Acts 2:38 - "Repent and be baptized, every one of you, in the name of Jesus Christ for the forgiveness of your sins."
Disclaimer: I do not identify with American/political 'Christianity'.
Wishing is one thing. Hope is the better thing. There is something beyond death. I don't know how anyone can think otherwise. Who else has the words of life?
We all find out
Why’d you be so pessimistic when there’s plenty of evidence that there is.
Or are you saying that billions of Buddhists and Hinduists are delusional?
It's not that they are delusional, it's that they can't prove it. They don't have evidence, they have faith.
Oh, you know, it's just someone that thinks everyone except them is wrong!
7 replies →
Our salvation is in psychedelic drugs. I'm serious.
There is no cheaper way to turn swine into gentlemen.
Now we just need to trick them into eating the stuff.
I agree more/most folks ought to try them under the right circumstances (yada yada mental health caveat here), but I also know plenty of psychonauts who are complete pricks, even some who have broken through on DMT and are still complete wastes of oxygen as humans. Go figure.
They are a doorway to new perspectives. You still gotta internalize the message.
There was a drug called Rapamycin discussed in this Radiolab episode https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub
The drug supposedly helped delay the doctor's cancer and extend his lifespan until he stopped taking it, then it came back "with a vengeance" and he passed away. He wanted to stop taking it to verify whether it was actually working or not.
I wonder if it might help this person? He might have to be on it for life though.
Don't take my word for it though, this is FAR from my field of expertise.
This is an mTOR inhibitor, I believe there are others already in clinical trials. I know PIK3 inhibitors are used to block some cancers. Most inhibitors stop cancer for "a while" but cancer cells have the ability to circumvent pathway disruptions.
https://en.wikipedia.org/wiki/Sirolimus
https://en.wikipedia.org/wiki/MTOR_inhibitors
PI3K inhibitors only work if the tumour tests positive for that special mutation.
If we block someones ability to try novel procedures, how is that any different from blocking their right to assisted suicide?
A steel-man response would be that assisted suicide is more about pain reduction, whereas experimental drugs could have terrible side effects.
It isn't a convincing argument to me, because possible death avoidance is a higher level of morality to me, but harm reduction is extremely prevalent in medicine as a driving factor.
But we allow physician assisted suicide.
Strange isn't it? Almost sounds like soylent green. Maybe I'll skip McDonald's this week.
I think guaranteed death is much more different than potential death and potential cure.
It's a tough line to walk on, still.
The only guarantee in life, is death.
2 replies →
Because access to novel procedures gives us valuable data.
There is a clear problem, and a good idea here. (i.e. Right to Try) What needs to happen to make this move forward?
I am getting so mentally exhausted learning about a specific problem, and then experiencing the helplessness of not knowing how to push on driving towards some mutually agreeable resolution.
Add in the fact that there is no way to seemingly coordinate the push towards a resolution. Individuals taking action without coordination feels just the same as taking no action at all. Are there any tools to coordinate the push and keep track of progress?
What about the right to refuse? I don’t think there actually is a problem here, there’s no reason for this Pharma company to provide an expensive untested drug- only potential negatives
I saw both of my parents go through cancer (they both, so far, survived), my wife has MS - so I was quite interested in the "perspective" treatments.
You have the whole usual bunch of idiots that will advertise magnetism and cosmic rays to cure you, then new treatments that may or may not be available in your country (but available in others) and finally the trial ones.
I discussed at length with an acquittance of mine who works in the clinic trial branch of a pharma and she first gave me the usual double blind trials explanation (which I am aware of), but then could not really answer why the pharma companies insist in not having people, for free, that would test if the treatment is not obviously lethal (or heavily impacting).
If I was faced with the perspective of dying soon (or going through something like Alzheimer) I could not care less if the treatment is fatal to me. Again: not that is not working (this is something one can assess statistically through normal trials) but that it is clearly harmful.
This would at least be a clear indication of "don't try it" (or "be very careful monitoring for this and that")) if there are enough patients who react badly
Regulators are, in general, too sheltered and disconnected from the impact of their actions.
Incentives matter. When you get to make decisions that impact others, but not feel any of the costs associated with that, you do not have the correct incentives. I hope the staff of FDA read this and can’t sleep tonight. We can hope they feel some emotional pain, even if it is only some small subset of the pain they have and continue to cause to others.
FDA delenda est.
I would disagree with this. Regulators that I have worked with in US and EU knew what it meant. Maybe not the most amazing technical people I’ve ever worked with, but they were as competent as any random sample of pharma/tech types. Their jobs is to verify that you have completed all the valid documentation to demonstrate that your drug does what you claim it does. Their opinion on personal emotions are irrelevant. They are supposed to be guideline checkers.
I understand some people are checking boxes, with no space to consider their impact. Please generously reinterpret my point to extend to their management stack and the political establishment that is responsible for the system.
Those who establish, support and tolerate that system should be as directly exposed to its consequences as practicable. It is good for them to see these stories and feel the consequences of their decisions.
2 replies →
I think the consideration that an article like this misses is the unintended consequences of speeding a process up / reducing the criteria for review, approval, etc.
I think we can all see incidents of where some oversight process is loosened because of some legitimate desire to help some, but then you learn that the bad / incompetent / exploitative actors come out of the woodwork to test and take advantage of the changing of rules. Not even saying intentionally, but just by sheer numbers, the change you made allowed things that were being held back by (hopefully proper) regulation to now happen.
Anyway, not saying that the FDA and other bodies couldn't move faster -- that is always the case. And there will always be examples of people/cases stuck in the cracks with legitimately sad situations.
But I would hope that people reading such stories think about why there is a process. It's not like the FDA's purpose in life is to stop people from benefitting from new treatments. It's to prevent the flood of bad effects of companies/individuals from being able to say they offer some drug that doesn't work in the way it says it does.
>I think the consideration that an article like this misses is the unintended consequences of speeding a process up / reducing the criteria for review, approval, etc.
In general I feel like the sick should not be held responsible for the unintended consequences of things. The principle that it is better for 10 guilty men to go free than 1 innocent man to be punished applies here as well. How many suicides have happened because it took this long for the use of psychedelics and THC for the treatment of depression and PTSD to be approved (partially, in some places). How many people are suffering today, right now in pain or under the care of doctors they would otherwise leave for poor treatment but the "opioid crisis" has limited their access to the treatments they need? I've faced this problem personally more than once, and while I am sympathetic to the law of unintended consequences, I just can't be convinced that it is the duty of myself or my loved ones to suffer because someone else might abuse something. There is a balancing act to be had for sure, but any borderline case should ALWAYS err on the side of reducing the current actual harm in favor of preventing a nebulous potential future harm.
If he's going to die why not give him the option to try medicine that is developed by large players with a good reputation? Weighing historical success into the process seems to make sense to me. Beta programs from Google are usually very functional...
Some FDA APPROVED cancer medication cause many severe side effects, for example, Opdivo/Nivolumab[1], my father used it and it seems to help, but caused other long term side effects, which seems will never pass. 1: https://www.opdivo.com/potential-side-effects
Another topic for discussion related to this (and I hope we can be detached enough to discuss the intellectual side of this impersonally):
Even if the drug/treatment method were approved, how much would this cost, would the author even be able to pay for / have the insurance company pay for the treatment?
And by the way, what limits are there on the price of a drug that an insurance company or the government will cough up the money to pay, for one person's extension to life for a couple years?
If someone has a very rare or just very advanced cancer, how much should the rest of us (as individuals paying taxes/premiums/etc) be on the hook for paying for last ditch efforts to prolong that person's life?
These are genuine questions I think are legitimate to ask, if not in polite conversation, then at least at the level of policymaking bodies in govt or insurance companies. I'm sure that people in the UK are quite familiar with this concept or debate.
You cannot just say you'll pay whatever it takes to save someone's life no matter what the circumstances.
I really sympathize with the author and feel his position has great moral clarity.
Wish there was some country or state where you could try more freely.
I get that the FDA is bad but how come there is no country anywhere on earth where these treatments are legal and available?
The FDA is not bad. The world has never had a shortage of liars, scammers, or snake oil salesmen. The term snake oil itself hearkens back to salesmen who would promise "medicines" to desperate people to con them out of their money.
Allowing trials to be bypassed and allowing people to pay for early access to unproven drugs would bring a flood of such be vendors and be bad for society, bad for medicine, and bad for ethics.
No one is advocating for "pay for access" or a means of bypassing trials that facilitate a "flood of [scammers]", so this is a straw man. You'd have to show why any design for relaxing regulation of trials is necessarily bad in aggregate.
The article even cites a case where the bureaucrats are confident in the safety of a trail drug but unable to approve for political reasons.
Not to mention the FDA allows plenty of snake oil supplements, etc. to be sold, so it's not particularly good at the goal you claim it's optimizing for.
2 replies →
Because the mRNA vaccine approach is just about as cutting edge as it gets right now and only a few countries on the planet are any good at it.
The same is true for a lot of cutting edge treatments.
It quite strictly limits where such treatments are likely to be available.
This is a very interesting question. Why are medicines regulated federally? As I understand it (and IANAL) doctors, pharmacists and nurses are regulated on a state by state basis.
> Why are medicines regulated federally? As I understand it (and IANAL) doctors, pharmacists and nurses are regulated on a state by state basis.
Dr's typically practice in ~1 state while drugs are available in all states simultaneously.
Fifty states - of varying ability - trying to independently qualify all available drugs would be a nightmare of redundancy.
It would be an extraordinary disaster to kick that regulation back to the states.
Florida would probably outlaw all mRNA technology. Their FDA would refuse to approve any mRNA-based therapies, and so on.
We have seen the disaster that approach can cause in healthcare, insurance, abortion (reproductive health broadly), gay rights, etc. It's insane that we have state by state drivers licensing as an example that is merely highly inconvenient.
It's not a good thing that doctors and nurses are regulated at the state level. It's a horrible thing that contributes to the US healthcare system's vast dysfunction.
I hope more and more medicine/science moves outside the reach of FDA. If someone is willing to pay for a treatment (or recreational product), and is reasonably informed/competent to decide the risks, and it's not a risk to anyone else, go for it. If someone tries to prevent consensual commerce (possibly while wearing a silly uniform or carrying a printed ID badge from a state), violate the law if on balance it's worth it to do so, and if it were literally my life at risk, I'd use whatever force required to accomplish the transaction. Hopefully treatment would be on the table before I lost the ability to run a carbine properly if needed.
Medical tourism is an excellent opportunity for "network state" and state alternatives. I already get virtually all elective medical care outside the US for commercial and service quality reasons, despite having US insurance.
two questions:
- where do you go, and why?
- how do you get your US insurance to cover/work with providers outside the US? does it just automatically work or…?
I mostly go to expat/tourist-focused high-end clinics in Asia (there are a bunch of options; mostly depends on which country you're going to be in -- Thailand, Singapore, Japan are particularly strong). You can get a really comprehensive physical (cardiac calcium, exercise stress test, imaging, comprehensive blood panels, multiple doctors/specialists, etc. for <$1k -- something comparable in the US would be $5-10k (e.g. https://my.clevelandclinic.org/florida/departments/executive...). I travel enough for work that I can just go a few days before/after a meeting or conference, so no incremental cost (maybe an extra day or two of hotel).
I do carry Blue Cross/Blue Shield PR coverage ("PPO Gold", $230/mo), although it doesn't cover anything outside of PR except for emergency care. I should probably get a secondary insurance plan (which might include full coverage outside the US, or might even include shorter visits to the US as well), but for now I'm comfortable self-insuring medical costs, particularly since I think I could get insurance negotiated rates in the US even if they're paid out of pocket.
Better quality, lower cost, than anything I've found in the US. I live in Puerto Rico, which has particularly bad medical care; if I lived in Boston or SFBA I'd possibly have a local doctor, but I haven't found anyone in PR, except for expat friends who are neurorads/etc., who is a competent doctor. "Have a pain? Get on a plane" is the plan, and I have medical evacuation insurance, an ALS bag in my house, etc. for that.
The other upside is my records remain under my control; they don't get put into some weird insurer/employer accessible system protected only by laws. I can request/receive raw files and keep them myself.
(So far, I don't really have any serious or chronic conditions besides being overweight and slightly high blood pressure, but if I had a screening discover cancer or something, I'd want to have full flexibility on how to proceed with that.)
(Relatedly, I've deferred getting a dental implant for a failed root canal since right before Covid, so currently looking for the best dental implant medical tourism option -- Mexico, Colombia, and Asia are all pretty solid. It's 3 visits (plus possibly orthodontics since it's been so long with a missing molar), but internationally is maybe $2-3k vs $5-15k.)
How horrible and frustrating. There is a fast-track approval procedure described here, I wonder why it doesn't apply to these treatments?
https://www.fda.gov/patients/fast-track-breakthrough-therapy...
There is some important context for the following comment:
“If anything goes wrong,” he argued, “think how bad it will look that we approved the drug so quickly.”
In the 1980s, when the comment was made, there were still people at the FDA who remembered the Thalidomide disaster, which would have been a lot worse had the FDA approved the drug. In the U.S. several thousand women took thalidomide during the clinical trials, and some doctors took it, too:
In one case, a doctor had been using thalidomide himself and prescribing it to his wife. In addition to the wife’s loss of vision, the doctor mentioned peripheral neuritis, nerve pain that is a side effect of thalidomide.
The other report is even more alarming — a nurse had given birth to a baby without arms or legs and, as a registered nurse, “she may have had access to the item.” (1)
Other countries including Canada, Taiwan, Japan, and West Germany did approve the drug or allowed it to be sold.
On December 2 1961, the drug was taken of the German and British markets, after several doctors brought up concerns as it appeared more and more plausible that thalidomide, when taken by pregnant women, was responsible for severe birth defects. Thought the Government of Canada was informed of these suspicions about the possible teratogenic effects of thalidomide, we had to wait until March 2 1962 for the Canadian authorities to react and, in their turn, withdraw thalidomide from the market. As unbelievable as it can appear, thalidomide was legally available in Canada for three full months after being withdrawn from its origin country. (2)
1. https://www.nytimes.com/2020/03/23/health/thalidomide-fda-do...
2. https://thalidomide.ca/en/the-canadian-tragedy/
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.
Gets complicated, fast, when you start considering the legal concept "of sound mind and body" - why it exists, what it means, when and where it finds use... For a good historical case, Jonestown.
"Regulation" vs "Information" also gets complicated, fast, when you consider global supply chains - for recentish news, checkout the stuff on heavy metals in Trader Joe's chocolate - how does all that information propagate to the final consumer? How does that consumer have the knowledge, skills, and time to process it?
(As with all things, IMHO, it's about balance, and, IMHO, balance comes from forces in opposition. "You are the ultimate authority on your body" is one force.)
Without socializing of medical costs I completely agree. But if you are asking other people to pay for a part of the consequences of your decisions then you should accept that those other people can constrain the decisions you can make.
Bigger problem is lawsuits by relatives.
And if you protect the drug companies and doctors against those lawsuits, then you open the door to them exploiting desperate people.
The US govt makes medical information available online perhaps to give a more informed decision.
"IL-6 Activities in the Tumour Microenvironment. Part 1"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765074/#:~:tex....
"Serum Level of Interleukin-6 in Patients with Oral Tongue Squamous cell Carcinoma"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461844/
"Interleukin-6 role in head and neck squamous cell carcinoma progression"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698512/
I also know from Google Scholar, that copper increases IL-6, penicillin breaks down into penicillamine, used to treat Wilson Disease, a copper metabolism difference, and I also know that Omega 3's look promising for reducing IL6.
https://pubmed.ncbi.nlm.nih.gov/29803716/
And thats just an example of a cursory look into SCC.
Socialised medical costs, isnt always a panacea, knowledge and honesty is the closest you will get to a panacea for medicine.
The problem with your scenario is when the consequences are unknown.
People who aren't in medicine really have a hard time understanding just how grisly the things the human body can go through might be.
Medical staff saw during COVID the mismatch between the degree of fear the average Joe had about the consequence of intubation and the degree of fear and panic of the average Joe when actually getting a tube down their throats.
A drug that goes wrong in a bad way can go REALLY wrong in a bad way. Dying from cancer sucks, but it's still several degrees less horrible than dying from your CNS being eaten away from an autoimmune response to an experimental drug which somehow leads to opiate-resistant neuropathic pain.
But if we simply caution "we don't know if this drug will cause horrible side effects" versus "this drug may likely cause unthinkable pain that we can't control in your last conscious moments" that's a very different level of informed consent.
You might be surprised by the number of doctors who privately lament how patients and patient families in general will so often choose to shoot for low odds outcomes that mean terrible conditions for the patient in their last months of life. Even when risks are known, people tend to be bad at actual risk assessment, and will downplay risks and focus on potential rewards, and this extends into medical care. And I'm skeptical that descriptions of what might go wrong versus actually seeing firsthand what it looks like when things go wrong still represents adequately informed.
So while in spirit I agree that completely criminalizing personal choice around consumption is not ideal, when there's insufficient data for truly informed consent I'm not sure I still see eye to eye on the topic.
I mean, fentanyl? Obviously it's a whole subject that could be unrolled/debated, but I don't have any interest in doing that today. Really, I thought I'd just point out one interesting and often unknown aspects of US/State law (assuming this is mostly a US-based forum; I know you said universal human right) - taking drugs isn't a crime anywhere that I'm aware of. Possession of them certainly is, but just having taken them is not.
Yeah.
It should be legal too. I'm not defending the use of it in any way, this is not about drugs but a more fundamental problem: governments deciding what you can and cannot put into your own body.
They should inform people about potential dangers and effects of substances, and try to prevent the underlying reasons for people to, say, do heroin or fentanyl.
But if someone wants to do it anyway, making it illegal just makes things worse as people will be stigmatized socially where they should be welcome/accepted the most, and they'll obtain the substance illegally and dangerously (who-knows-what-it's-laced-with and exact actual dosage) anyway.
So just inform and support the people but make it legal and relatively safer to consume for harm reduction.
But if someone wants to OD and kill themselves, I mean, it's sad but it's their own body and their own life.
1 reply →
If buying, selling, and possessing are all illegal, it's illegal for all practical purposes.
1 reply →
> anyone can take anything into their own bodies and governments can never, ever prevent them.
Thought experiment: There is a magic drug or parasite where any dosage (whether deliberate, accidental, or fraudulent) will force the person into a single-minded violent quest to get another dose.
For the next month, another hit is the most important thing in their world, even if that means selling everything they own, cutting off their own leg, or murdering their children. Repeated doses cause mental confusion and are eventually fatal.
Are you still comfortable saying that nobody can make any law against the distribution or consumption of THAT substance?
Not OP, but laws against distribution? Absolutely.
Laws against consumption? A terrible idea.
What we should want to do as a society is funnel people interested in trying things we think they really shouldn't do towards legal chokeponts that are less onerous than DIY access under controlled distribution but still allow for attempts at prevention of the end outcome.
The clearest example of this even more than your drug scenario would be a drug that just immediately kills the user.
There's a lot of people every year that seek out that end result. While some can fall under a narrow scope of legal options under dignity laws when faced with terminal situations, there's many who seek out that outcome without physical ailments.
If there were a legal way to seek it which was overall less traumatic of a route, but which was also only on the other end of intervention measures like counseling, how many lives might be saved as compared to the rather ineffective prohibition that we see today which largely fails to prevent access and use, but whose illegality does prevent aspects of both research and prevention that might otherwise occur if distribution was the only thing targeted in laws and not attempted consumption?
If people are aware of the life ruining consequences of a drug but value their own lives so poorly that it doesn't deter them from throwing them away to seek out a drug, then society doesn't have a drug problem as much as it has a human experience problem.
There's few things more cruel in concept than ensuring people keep living under conditions where they'd rather not live at all. Whether they are seeking that result all at once or gradually throwing their life away, criminalizing their seeking rather than the conditions that motivate their seeking is wildly messed up.
2 replies →
I would like this, if somehow the people giving you the things were required to do it for free. Because without that, it just looks like writing a blank check to fraudsters.
It doesn't matter if insurance companies aren't required to pay for it. People will max out credit cards, borrow from friends, and mortgage their house. All for something that could sit anywhere on the continuum of: does nothing to kills you immediately. Probably with a side of "did this rather than something that would have actually worked".
Devil's in the details. Suppose Pfizer wants to test a new acne drug based on radium nanoparticles fused to asbestos. It might work, and hey, if you can give a homeless guy $100 and a bottle of vodka to "voluntarily take it into his body" and let you watch to see what happens- that's so cheap! Why not give it a shot!
If the person is mentally able to make that decision for them selfs, then why not?
4 replies →
Should be, yes, I agree, however, we are extremely far from this, I don't even know how many hours I would need to travel to legally buy and smoke a pack of menthol cigarettes.
Agreed. The regulations are beyond ridiculous and definitely not for the greater good of the society, only to clear the names of bureaucrats and regulators.
[flagged]
[flagged]
I am so sorry for what's happening to this man, and I hope he finds peace in his last days.
the economics, ethics, and effectiveness around early approvals are really difficult to manage. companies have a strong incentive to get earlier approvals. but once the cat is out of the bag, it's hard to get it back in. if a sub-standard drug makes it to market and gains wide adoption, it makes later drug trials of more effective drugs really hard. where's the outrage for potential beneficiaries of better therapeutics?
I don't mean to say this man and others shouldn't get a chance at a hail mary when they're staring down death. just, it's risky business for others in the future. I hope the best for him and others.
I don’t know why, but this was heart breaking to read. I don’t think it was meant to be.
I’m not a Dr., I’m not recommending anything, but you might want to look into the following:
I see the FDA approved drug cemiplimab-rwlc for squamous cell. https://www.skincancer.org/blog/new-treatment-for-advanced-c...
And if your willing to consider alternative therapies there is fenbendazole(see joe tippens protocol). It’s a dog dewormer and is available at pet stores as panacur-c.
Also see Albendazole, Flubendazole.
Things don't happen in a vacuum. It’s understandable that people want access to the experimental medicine for themselves or their loved ones when the fear of god has been put into them. When one has nothing to loose, what’s there to loose?
Unfortunately it’s our dignity (or at least others diagnosed with „x remaining months“). As soon as this becomes normalized, the moral impetus will change that those wo didn’t make it, probably weren’t brave enough to try the new stuff.
(not an MD) The FDA does allow for compassionate use of experimental drugs. My understanding the many early stage drugs are tested this way, but access is limited to trial centers. The author should try search drug trials database to see there's a group that is recruiting: https://classic.clinicaltrials.gov/ct2/results?cond=Head+Nec... My brother is a physician who is working with patients in drug trials. He had the very good fortune to see an experimental drug successfully treat a very sick, critical patient who was declared a candidate for "compassionate use".
This seems bad. Help me understand.
In what ways does always letting individuals choose to take an experimental drug not work, if we make sure they know what is known and what is not? They are desperate, and that's a horrible place from where to make a decision, but dying is a really bad alternative.
What are the pitfalls that would allow for this to not always be the option? How would this go more horribly wrong than just letting these people die?
If it were for science alone, it might be fine. The problem is when Steve Jobs is sick and I walk up to him and sell him an experimental cure for $2,000,000,000. He can trivially pay it, but I have a huge incentive to lie. At a smaller scale, a more efficient conman can take all of someone's assets. And not just the dying person's. How many people wouldn't sacrifice everything to save a spouse's life or their child's?
The other concern is when you turn down medicine that might work for snakeoil that doesn't.
The lying seems like the problem there. Present the patient with accurate records of previous trials and outcomes, let them make an informed decision (with help from their doctor, if they're not scientifically literate) and I don't see a problem.
Could the former be fixed by requiring experimental drugs to be free of charge, or would that break how drug roll-out works? Somebody suggested an escrow account in this thread, which also seemed interesting.
2 replies →
I'm sorry this is happening to you. Thank you for fighting to improve SCC outcomes for yourself and others. Please keep us updated with your progress.
Not having some level of “right to try” is abhorrent.
Having said that there are two elements that I’m not quite sure how to adjudicate 1) where does one draw the line with regards to how sick someone needs to be to qualify for right to try, and 2) how do ensure that patients are actually getting a treatment with some resonance likelihood of success as opposed to some snake oil?
I thought the recent New Yorker article on FDA's drug approval policies, "When Dying Patients Want Unproven Drugs", was balanced, insightful, and well-written. It covers Thalidomide, and focuses on ALS and HIV. https://archive.is/u6vmI
> think how bad it will look that we approved the drug so quickly
The media (both traditional ans social) owns a large chunk of the underlying blame, due to their rush to create simplistic narratives in the wake of anything that "goes wrong" without nuance or examination of tradeoffs.
Unclear to me why clinical trials seem unavailable to him, which is how he would gain access to these treatments. The major cancer centers generally will have options for his exact situation, though sometimes they require he finish conventional and salvage treatments first.
I understood your question to mean “why can’t he have access to clinical trials?”
A person has to qualify for the clinical trial by meeting a set of specific set criteria to ensure the results are interpreted with the least amount of error.
He wrote "The FDA was loathe to approve initial mRNA human trials". The implication seems to be that if not for this added delay, this potential treatment would be further along.
That doesn’t make a ton of sense, because there are plenty of phase 1 early stage trials at the largest medical centers in the country that use pre-“FDA approved drugs“. The whole purpose of the early trials is for the companies to go get FDA approval.
If he said he went to Mayo, MD Anderson, Harvard, Sloan Kettering, and none of the trials were available to him that would make a little more sense. But a great number of the trials in his disease site are for treatment refractory patients, so it’s pretty surprising there’s no apparent trials for him.
Highly relevant: research on ways to accelerate the medical-trial process. Here is one example from JASA: https://doi.org/10.1198/016214504000001790.
This is blaming the FDA for lack of treatment, not the recentness of the treatment.
That all the MRNA treatments they refer to are in trials tells you everything you need to know: we don't know which work, we don't know how effective they are, and we don't know what they work on.
It is possible to enroll in trials for these treatments, but as they say they "may" be denied as they're so far along. But that's what you want: if a trial takes someone on who would be highly likely to die even if the treatment works then depending on the trial size it's possible that that one patient might skew the results such that the treatment is denied, or alternatively, another person who applied for the trial gets denied even though they had a higher likelihood of survival.
I can understand it being incredibly hard for this guy, but we have been through the alternative:
* Snake oil treatments: drugs that do nothing but bankrupt people
* Actively harmful treatments: drugs that literally make things worse, while bankrupting people
* Paid trial scams: you can pay to be part of a trial, which immediately allows for the above two despite a regulatory environment that ostensibly requires trials.
etc
Things like the FDA exist in response to prior actions, and once they've existed for a while, people forget that the only reason that they don't seem necessary, is because they are there. Much like the "unnecessary" financial regulations that were removed, and immediately resulted in banks creating the Great Recession.
Hence, it is not possible for the FDA to create a "patients can be 'treated' with untested treatments" loophole that is not trivially exploitable by the kinds of people that resulted in the FDA existing in the first place.
Ok, so how do we fix this? Can we put this community into action to fix this problem?
This is after all a group full of hackers. I don’t know this domain area, but isn’t there anything we can start or do to change this obviously stupid and immoral system?
Blaming the FDA is popular but the problem is not the FDA itself. Drug manufacturers are part of the problem.
1. When the FDA has fast-tracked drugs, drug makers have taken advantage of this to hide data, lie, and refuse to comply with timelines for proving those drugs work. https://www.npr.org/sections/health-shots/2022/07/22/1110830...
2. When these accelerated drugs are found to not work or cause harm, the manufacturers continue to push for them and the FDA has tremendous trouble trying to their approval revoked. https://apnews.com/article/science-health-medication-busines...
3. Accelerated drug approval gets mired in advertising. The general public has no idea how to judge if a drug works or not. Plenty of people believe that homeopathy works. The FDA gets massive pushback when trying to take a drug that is worthless away, because people think it works. This hurts us all and creates an incentive for companies to hide data and deceive customers.
4. The FDA is as fast or faster than the Canadian or EU equivalents. The FDA is not specifically slow, bureaucracy everywhere has become much slower because there are no incentives to be fast but countless incentives to be slow.
5. Lawsuits. It's easy to say "I'm hurting, I'll take anything". But, then, there are rights you cannot give away. If a drug harms you, you will sue. If it kills you, your family will sue. The whole system is bogged down by lawsuits with massive disproportionate payouts. The early biotech companies and scientists involved often cannot deal with even a mistaken lawsuit.
We need a much more comprehensive overhaul of the system, starting with open access laws to all data pertaining to any drugs that are on the market (no manufacturer can keep anything secret for a drug that people take), an FDA that has much more authority and much less industry capture, medical tort reform, to create a system where in exchange it actually makes sense to provide fast tracked approval.
You're missing the part where the FDA has a revolving door with the biggest pharma companies. To think the FDA is some flawed, but impartial, judge of drugs is the key problem. The FDA is controlled by big pharma. No more, no less.
Huh? I literally said that.
But that's not the main problem here. You would expect the FDA to approve everything by that theory.
As other comments have pointed out, I'm not sure why the author can't access experimental therapies. Clinical trials or even compassionate use program (prior to FDA approval) are very common.
When a gov org cares about how it will "look" over wether it kills you - you live under tyranny.
A common example why government doesn't solve problems well. Because it's an absolute governing law, there's nowhere else to turn to. This creates an industry of snake oil that preys upon people both as regulated medicine and homeopathic remedies. In practice vertical integration is a requirement for economies of scale. This means all medicines must be created by singular centralized corporations. These corps buy out the regulatory and now we have an incredibly inefficient and locked out market that prevents innovation.
All orgs should be sunset after 20 years by law. Repeal the FDA, replace it.
You should also try immunotherapy (pembrolizumab) with chemo if your CPS is >1% before experimental early phase trials.
Jake, even in the face of declining health, don’t despair. I know it’s difficult but please, don’t lose hope.
The reality of cancer is a bit paralysing to anyone who has had direct exposure to it and there is nothing really overstated about it in the common sense of culture. Everyone’s fight is different, because there are so many paths to take and they keep changing as research advances, but the time available is limited. Besides being restricted, cancer drugs are also notoriously expensive, but for the more self-determined individual there is the option of off-shore pharmacies (many based out of India) and perhaps even Chinese chemical labs (anything on AliBaba must be assumed to be completely unreliable; however, some of the labs which are referenced by scientific papers as suppliers are actually happy to do business after only a little bit of social engineering). Unfortunately this approach is limited to relatively simple pharmacological interventions; anything that requires complex medical procedures (including palliative care) and has to happen in a hospital will require normal legal compliance and the cooperation of a doctor. There are stories of people who have gone far and beyond to enrol into cutting edge clinical trials [1] – usually with the energetic support of a loved one. In those cases, even with the consent of a doctor, the logistics and expenses aren’t trivial. There is much to say in general about the questionable role of institutions who gate-keep access to medical procedures under the pretext of protecting reckless consumers – but it wouldn’t feel right to steer the conversation too much away from cancer.
> This makes it nearly impossible for patients to find an appropriate clinical trial, discouraging all but the most stubborn–people like Mike Hindt, and people like Stephanie Florence. By her own admission, Florence, 44, a photographer living in Lewiston, Idaho, had to “bulldoze” her way into a trial by being persistent to the point of obnoxiousness.
> When she found out she was a candidate for a new trial, she also learned another hard truth: trials don’t come to patients. Patients have to go to the trials.
> In August, she and her husband drove from Raleigh to Boston, despite having no place to stay. After a week in a hotel room paid for by their daughter, they wrote about their circumstances on a community blog. Several people in the area offered the couple rent-free housing during Price’s treatment. In order to pay for food and other expenses, the couple are trying to sell their home, and Price’s husband, laid off from his job at IBM, took a couple of part-time shifts a week at the outdoor-apparel store REI.
[1] https://time.com/4270345/immunotherapy-pembro-clinical-trial...
This could change if there was enough political pressure. Easier said then done, but it should be done.
Spare the condokescenes, spoilt he action. Less wasteful comments, more letters to representatives.
Courage and best of luck for jake, his closed ones and anybody hit by hard to cure diseases.
Trump got a federal Right to Try experimental drugs act passed in 2018:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309195/
Not sure how this intersects with the author's reality. It is sad to see article after article spewing nothing but hatred towards Trump --almost purely from an ideological perspective-- when something like this could help so many.
This, in more ways than one, demonstrates how difficult of a problem this is. When people's lives become game pieces in political battles, the people lose and politicians, well, use them to score points towards their own career objectives.
I read in a comment that the author lives in NY, where, apparently, Right to Try isn't available. If find this interesting when a federal law has been in place since 2018.
This is one of the things that can be perplexing about the US system of government. Here we have a state preventing people from having access to treatments that could materially affect their illness when federal laws allow it.
While I do understand the many advantages of the independence granted to states by the US constitution, sometimes it feels like the US has devolved into a fifty regions pretending to be united as a nation when they are actually not and, as a result, end-up conspiring to damage the very societies they claim to protect.
Education is another example of this. All nations with excellent systems of education (and the results to prove it) have national-level planning, management and standards. In the US, not only is our system of education fragmented at the State level. Our schools are run by fucking unions organized as districts, each with their own axe to grind. It is no surprise the results are what they are.
We somehow manage to extend some of this "excellence" (sarcasm) into every level of healthcare.
According to wikipedia, many types of squamous cell carcinomas are associated with HPV infection. [0]
Another area where the US has lagged which would prevent a lot of these cancers from ever developing in the first place is HPV vaccination. Last I heard it was only females who were being routinely vaccinated, and relatively recently at that. We should really be prioritizing eradication of HPV.
[0] https://en.wikipedia.org/wiki/Squamous_cell_carcinoma#By_bod...
separate efficacy testing from safety testing
For the record, FDA has fast track / breakthrough therapy options:
https://www.fda.gov/patients/learn-about-drug-and-device-app...
Biden's Moonshot program is trying to drive money to support new innovations:
https://www.whitehouse.gov/cancermoonshot/
There's a wild book from 2006 called Overdose (by Richard Epstein), that makes a more or less libertarian argument for deregulation of the drug industry. What the book misses is that before the FDA and the Pure Food and Drug Act is that anyone who thought they could make a buck by poisoning as many people as possible did exactly that. And, especially given the "tort reform" prevalent in red states, there is fairly minimal disincentive for corporations to kill people in the US.
There is a religion. In it, good people are wealthy. Bad people, less so.
It's a popular religion among the well-to-do. As you might imagine.
Must feel especially shitty to have your freedom curtailed like this, looking at the probable end of your life.
Anyone more knowledgeable know why they can't file for a single patient IND, assuming the vaccine is even acquirable?
There is no 100% correct answer here. As soon as you speed up the process, there are still going to be people that just miss out, and then we will have people saying 4 months is too long, it should take 2 months, or let AI approve it, etc. Desperation skews perspective.
The issue with having a standardized approach to people getting experimental drugs is it opens up its own kind of mini-market unless the implication is they would be required to be free by law. And desperation is not the right mindset to make law or rational decisions.
Not trying to sound heartless, its just not as easy as saying "go faster".
On the contrary, I personally believe it's deeply immoral to tell a dying person to "just wait, it's for your own good".
Holy christ how did AI make it even in this conversation!?!
[flagged]
Couldn't agree more. There is literally nothing to lose, and potential to save a life.
Blocking this is effectively murder.
4 replies →
...why?
6 replies →
[dead]
[dead]