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.
Sure thing, I updated my profile with my real email. I certainly don't expect you to remember me, but you might remember my buddy Atish, and I hope you know that you left a massive impression on both him and me. As kids fresh out of high school, you were (and frankly, you still are) the guy we looked up to. Thanks for being 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 Bout one seemed to be in remission and all clear sounded only to be rescinded a few months later, second run was a negative outcome.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.
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.
It depends what you consider the outcome to be, by virtue of being a 39 y/o with early recurrent and possibly oligometastatic disease he is in the definitively palliative-intent treatment category so everything is a long shot.
Really the best and only chance for curative intent with most cancers is radical resection with negative margins which unfortunately did not work here (most likely due to micrometastatic disease and perineurial invasion). All of these new and fancy systemic options are not believed or intended to be curative-intent.
If we're talking about meaningful prolongation of life the best treatment would be a PD-L1 inhibitor like pembrolizumab if he has expression. He doesn't mention systemic/immunotherapy in his post but on the donation page his brother does so I'm unsure if he's in the early resistance/treatment failure arm for pembro, if that's the case it's very devastating.
He's correct that gem/plat chemo isn't great but it's something. Patients in his position are best served in clinical trials (also in the treatment guidelines).
With that said it also seems he had an aggressive bone cancer in his childhood, this suggests something unique to this person (e.g. some genetic driver mutation or hereditary cancer syndrome) that may complicate any of this prognostication. Unfortunately something very atypical and aggressive is happening in this person.
H&N SCC in younger patients or HPV+ usually has good outcomes.
Given his history it's probably not relevant to this case but best advice for any HN reader is to go get your HPV vaccine and reduce the risk of SCC.
Hey thanks for this post. You sound very knowledgeable.
Couple things: Jake’s SCC is non-HPV. He did Keytruda, and it had no effect. He’s being treated at the Mayo clinic where most of the oncologists were ambivalent about chemotherapy. He’s beginning platinum based chemo on Monday as a hail mary to try to kill this stuff.
And yeah — all the doctors have been flummoxed by the aggression of this cancer. It was the same when he had sarcoma twenty years ago.
“The Right to Try Act is one way for patients who have been diagnosed with life-threatening diseases or conditions who have tried all approved treatment options and who are unable to participate in a clinical trial to access certain investigational treatment options.“
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.
> Would this not also open the door for any snakeoil salesman to prey on what might be medically "hopeless" cases?
If you're diagnosed with something uncurable, then by definition you have a doctor or a medical team that has performed the diagnosis and is overseeing your treatment. There is, invariably, some form of treatment; in extremis, even "here, I've booked you into a hospice where they're going to load you up on opiates" is a form of treatment.
Any experimental drugs you're administered would go through your doctor or medical team. If those drugs are transparently snake oil, they should usually be very strongly advised against. If they have a halfway plausible mechanism, doc will probably say, "go ahead, roll the dice."
In any case, the snake oil salesmen aren't preying on sick people alone -- it's the sick person, plus the professionals who are in his corner, plus family and friends, etc. I don't think it would necessarily be trivial to make lots of money peddling something known to have no efficacy.
On a much more general philosophical note, there was much debate in Ancient China between Legalists, who viewed humanity as inherently evil, and Confucianists, who viewed humanity as inherently good. Where you come down in this debate seems to depends on that view. If you believe that men are inherently evil wreckers, you need stringent and indeed draconian regulations to keep them in place. If you believe that men are good, and that lives saved are on balance the greater aim, you should argue against draconian regulations and limitations on treatments.
The obvious case is that some are evil and some are good. And that's enough for the evil people to find the good people. (This is how Internet-connected computers secure works / fails.)
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.
> 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.
Should we at least demand more specific criteria than "X _might_ save their life", like threshold of suggestive evidence? There will always be lots of stuff that hasn't been closely studied, the effects of which we can only partially describe. You could isolate any new molecule from some previously unknown bacterium and say it "might" be a treatment for any disease, but that's just a statement of our own ignorance right?
If we say, "so long as it hasn't been conclusively shown to _not_ beneficial for the patient's disease, then it _might_ help them, so it should be fair game", then that seems to open the door to quacks selling snake oil to desperate dying people and their families. And of the unenumerable list of potential "it might work because we haven't yet shown that it doesn't" chemicals, why shouldn't unethical practices pick the most expensive options available?
"Of course you must understand there can be no guarantees with any treatment, and this may be a long shot, and precisely because of the lack of prior studies we cannot even give you any efficacy numbers. But we're at the cutting edge of medical science! Please make out a check for $500k and sign this waver and we can begin treatment as soon as possible."
> Should we at least demand more specific criteria than "X _might_ save their life", like threshold of suggestive evidence? There will always be lots of stuff that hasn't been closely studied, the effects of which we can only partially describe.
We do, it's part of the FDA process and is determined on a case-by-case basis considering alternative treatments, disease course and intervention safety amongst other variables.
It's how the vast majority of stroke and novel cancer therapies are currently being approved.
> 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.
You're assuming a therapeutic not tested in humans has a better chance of saving someone's life than something tested and available. Do you have any evidence to support this?
> 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:
There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials
comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than
ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data,
however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.
This review compared the effects of amisulpride with those of other so called second generation (atypical) antipsychotic drugs. For half
of the possible comparisons not a single relevant study could be identified. Based on very limited data there was no difference in efficacy
comparing amisulpride with olanzapine and risperidone, but a certain advantage compared with ziprasidone. Amisulpride was associated
with less weight gain than risperidone and olanzapine.
What's so tragic about this? Equally efficacious antipsychotics are available. Once again the alternative to non-approved drug isn't nothing or inferior substance.
I will concede that legacy off-patent drugs are part of the "very limited" gap with the FDA, this doesn't hold for new drug discoveries as discussed in the article.
Even then, there is an ongoing US trial for amisulpride and the substance is approved for nausea/vomiting (granted not in oral form).
"A comprehensive meta-analysis published in 2019 in JAMA that compared 32 oral antipsychotics helped solidify the sentiments shared by Kahn and other investigators who have conducted clinical studies with amisulpride. That meta-analysis identified amisulpride as the second most effective antipsychotic at reducing overall symptoms in schizophrenia patients (behind clozapine) and the most effective in terms of reducing positive symptoms. The analysis also ranked amisulpride better than clozapine in terms of tolerability and side effects."
> Antipsychotics are incredibly important medications for a lot of people.
Agree.
> It really matters that amisulpride is not available.
Not sure about this, I'm not a psychiatric expert but my cursory lit review shows conflicting meta-analysis as to whether amisulpride is better than 2nd gen. Although your source is newer Cochrane is generally the gold-standard on SRs and the included studies in the 2019 JAMA article predate the Cochrane review, they detail the limitations of comparison.
Looking at Canada, amisulpride is limited to special access and is also not first line.
The UK pharmacotherapy guidelines are also waffly and cite limited evidence to guide firs-line decision making.
A systematic-review from China showed different side-effect profile for both, hard to say which is better. Amisulpride was cheaper.
In any case old drugs that were never approved are part of that "very little" I was referring to that fall through the cracks.
Not sure I'd call this one tragic though given that other countries also don't use it or limit access and there are good alternatives.
The problem with "there are similar efficacy rate alternatives" is that, for most psychiatric drugs, it's not necessarily the _same_ population that is helped by two different drugs at similar efficacy for the same issue, even if the total success rates are comparable.
A number of people have tried many different individual or combinations of treatments before finding something workable, or close enough to workable that you can paper over the cracks. I would strongly suggest against concluding the lack of access to something isn't an issue for some patients because they have alternatives, without very compelling evidence.
A story from my recent past - I've had, historically, no issues swapping between different generic manufacturers, or name brand and generic, if someone stopped making something I was taking, or I moved and the pharmacies stocked different versions, or whatever. So a little over a month ago, when I noticed my meds looked visibly different after getting them filled, I checked to be sure they hadn't given me the wrong thing, but no, same dose, different generic manufacturer, and I stopped worrying.
...until I started getting extremely nauseous to the point of being debilitating, for 6-8 hours every time, when I take this medication twice a day. So I went back and tried the third generic manufacturer the pharmacy had, after a few days of making sure it wasn't a fluke, and the third one had the same issue. We finally ended up switching to the extended release version of the med, which had still more different manufacturers, and did not have this issue, since the first manufacturer had a shortage for over a month and counting.
Medications are a lot less interchangeable than we might hope.
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 do not live in a state with a Right to Try law. Can I still use Right to Try?
"Yes. S.204 makes Right to Try the law of the land. So long as a patient and treatment meet the qualifications of the federal law, Right to Try applies, regardless of whether the patient’s state adopted Right to Try."
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.
A simple way to stem most snake oil is to put all payments for snake oil treatments into escrow till the treatment is approved.
Then the snake oil manufacturer can peddle their unapproved treatment to as many people as they like, but they are losing money on every dose unless the treatment turns out to be safe and effective.
Obviously you need a big team of scientists on the approval panel to make sure no snake oil salesmen are faking trial data to get their payday, but that seems solvable.
> A simple way to stem most snake oil is to put all payments for snake oil treatments into escrow till the treatment is approved.
Even simpler is to prohibit payments for these experimental treatments, but let people who whould die anyway participate in them as long as it is free for them. In return the drug companies could use the outcomes as data points towards their aproval applications.
Why would a drug manufacturer do that? Why would they offeir their advanced but as of yet unaproved drugs for free? It is true it would cost them the manufacturing cost of the drug, but what they get in return is data on how efficient/safe the drug is. Assuming the drug works well they could use that data to prove their case and get approval. And if it is safe and has the desired effect they get their aproval and they could then charge for their drug as usual.
This sets the right incentives for the drug company. If they know they are selling snake oil they would be crazy to offer it for free, especially because all it would do is to prove that it does not work. If they think it can work they gamble with their own money. Which is good because the drug company knows the most about their own drug. The patient in general is not knowledgeable enough to evaluate the chances of an experimental therapy, but the drug company is.
> Even simpler is to prohibit payments for these experimental treatments, but let people who whould die anyway participate in them as long as it is free for them. In return the drug companies could use the outcomes as data points towards their aproval applications.
That would never happen for good reason. Drug companies would have every incentive to bias the results towards approval by giving the drugs to detain patients. I’m not exaggerating when I say this might be the worst idea I’ve read in this entire thread.
> Drug companies would have every incentive to bias the results towards approval by giving the drugs to detain patients.
What do you mean “detain” patients? Remember we are talking about people who have a terminal illness with no known cure. How can drug companies “bias the results”? Obviously I’m not saying we take anything they say as gospel, but in short order these patients are expected to die. If a drug managed to cure them that would be quite hard to falsify don’t you think?
> I’m not exaggerating when I say this might be the worst idea I’ve read in this entire thread.
Well, thank you. I aim to please. Are you sure that you understood the idea well? If you are, could you please explain with more words what is the misbehaviour you are worried the drug companies would commit?
Choosing appropriate patients will lead to longer survival rate unrelated to the drug in question. The whole point of double-blind studies is to avoid this.
> Well, thank you. I aim to please. Are you sure that you understood the idea well? If you are, could you please explain with more words what is the misbehaviour you are worried the drug companies would commit?
I did understood you. You, however, don't seem to understand statistics or economics. Your idea directly incentivizes drug companies to choose patients more likely to make their drugs look better. It is a truly horrible idea.
> Your idea directly incentivizes drug companies to choose patients more likely to make their drugs look better.
Yes. So? The whole patient group in question is destined to die fast. The best we currently can offer them is aleviate their discomfort and help them come to terms with their demise. If the drug company can identify a subgroup who they can possibly save and actually help those that is winning.
> You, however, don't seem to understand statistics or economics.
And you are abrasive and rude. These exclamations don’t add much of anything to the conversation. If there is something particular I am overlooking please adress that instead of speculating about the areas you think I am deficient in. Thank you.
You are aproaching it as if the question we are asking is if this is the best study design. But that is not the question we are asking. There is a patient who we believe is about to die soon. In comes a drug manufacturer and says to the patient: “you do not have to die. I think I have the cure for you”. The patient wants the drug the drug manufacturer is offering. The question is if we are to interject and stop the drug manufacturer giving the patient the drug, and if so under what circumstances.
I am saying: “yes, we should stop the drug manufacturer if the drug is not proven to be effective yet, and he is asking for money for it. There is too much of a chance that the drug manufacturer is a snake oil salesman in disguise and only wants to extract the wealth from the patient and the patient’s family. But if he is honest they can give the drug for free.”
In turn you are saying. “We should stop the drug manufacturer giving the unproven drug to the dying patient even if they are giving it for free, because it is possible that they cherry picked this patient. So though luck dear patient, you must die in the name of scientific rigour. I hope you understand.”
> You are aproaching it as if the question we are asking is if this is the best study design. But that is not the question we are asking. There is a patient who we believe is about to die soon. In comes a drug manufacturer and says to the patient: “you do not have to die. I think I have the cure for you”. The patient wants the drug the drug manufacturer is offering. The question is if we are to interject and stop the drug manufacturer giving the patient the drug, and if so under what circumstances.
This is already largely possible in most states and called "right to try".
> Do I understand you right?
No you seem not to be. Giving away drugs is fine and largely already possible. Choosing patients and then pretending that the data gathered has any reasonable statistical validity when considering general approval of a drug is totally crazy. I think there is essentially zero chance the FDA would ever go for an idea with such overt conflicts of interest so I'm happy your idea will never turn into reality.
> This is already largely possible in most states and called "right to try".
The article’s author is convinced it is not covering them. Do you know otherwise? Perhaps you should let them know. You might save a life.
> Choosing patients and then pretending that the data gathered has any reasonable statistical validity when considering general approval of a drug is totally crazy.
Would like to mention that it is your adition that the drug manufacturer chooses the patients. It was not part of my original comment. And it is not core to the idea.
One can simply imagine a protocol where the manufacturer declares their criteria (what condition, what severity[1]) and how many doses they are able to provide and those “places” get filled up with volunteers. And this of course can be made even more buletproof.
1: and before you point it out, of course if the manufacturer is only willing to test their drug on not-so-bad-but-dying people then they get approval to be used on the same selection.
What do you mean with "by giving the drugs to detain patients"? Is that a typo? I don't see how companies holding on to terminally-ill patients makes the trial results look more favourable. Are you suggesting that companies might not release the bodies of the patients that died during the trial?
This plan seems to have excellent incentive alignment and basically mirrors the system in place, but without the need to be approved for clinical trials.
Experimental treatments being available to people with no options (there must be no applicable option with a proven probability of success or this becomes very questionable) could save drug companies millions-billions in the off chance that it proves to be incompatible with human testing or fails to produce the expected effects in humans.
I would take this up a notch or two for patients in a short-range situation that is certainly fatal, opening the door for them to try treatments that have just barely crossed en-vidrio and seem to have acceptable toxicity in mouse models. This would essentially be donating one’s body to science but in a much more useful form, with the side benefit of a slim chance of life extension.
This could benefit humanity by significantly reducing time to market for some drugs and cutting costs on eventual dead-ends.
Of course, for actual efficacy, but you can tell if a treatment has a negative reaction or fails to effect the expected physiology in the expected way with a very small number of samples.
If everyone you give it to dies from reactions, or the expected effects seem to be happening on a physiological level, you don’t know much about efficacy but you do know a lot more about the eventual prospects for an actual clinical trial. It’s basically an extension of en-vidrio testing.
No, that does not set the right incentives. You have completely written off the harm of dangerous or deadly drugs.
The HepC drug Sovaldi brought in around $50B-100B in sales, but probably costs less than $50 to administer. Under your scheme it would make economic sense for a company to kill 1,000,000,000 people testing variants until they chance upon the right one because they incur no costs for administering deadly experiments.
The problem with your scheme is that human lives are valuable. A unsafe drug that causes harm or death is immensely destructive. If we want to be completely reductive, the actuarial value of a human life is around $10,000,000. A unsafe drug could kill the person resulting in a $10M loss to society. Therefore, the company should be required to escrow $10M per person until the treatment is done, paid out proportionally to any potential death or harm in excess of the gold standard treatment. Only then would the incentives be reasonably aligned.
This is obviously a very reductive treatment, but it helps illustrate the problems with unrestricted testing.
> You have completely written off the harm of dangerous or deadly drugs.
I was only talking about testing on people who we know are going to die fast because of their condition, and we do not have a way to save them in any other way. And naturally only with their consent. People who have a ticking clock and therefore willing to try anything.
This is the context the article in question talks about.
I think you forgot to price in the fact that some people live with what is effectively a time limit sometimes counted in months or weeks (like the person from the linked article).
> Even simpler is to prohibit payments for these experimental treatments, but let people who whould die anyway participate in them as long as it is free for them. In return the drug companies could use the outcomes as data points towards their aproval applications.
Hell I'd even approve my tax money to go to those companies which end up saving lives as reward.
I love the innovative thinking here but I can easily think of a way to game this system. Snake Oil LLC mounts a PR campaign claiming the governmen is trying to shut them down by delaying approvals so they can't get their money so they can't undercut Big Pharma. If Snake Oil (TM) doesn't work, why have patients ponied up $X billion in fees over the years?
You have enough stories like this (plus there will inevitably be some mistakes by the FDA that will be shown to be proof of government perfidy) and the conspiracy theories will have a field day and fuel a black market.
I mean, this is just a “sufficient misinformation” argument that could be levied against literally any kind of policy. No policy can survive sufficient misinformation.
The point I am making is not a rebuttal to this specific proposal but that any such change will have an attack vector. Hell, the reason we are having this discussion is because of the (unfortunate) case of someone not being served by the current policy. Any new change to the policy will have such cases which will lead to this same discussion.
Creating an equitable drug approval process is a true dilemma.
But at the end of the day, failed treatments still kill people. Some may choose the experimental treatment, and die, over the crappy chemo, which gives them a chance to live. Escrow won’t bring them back.
If I knew I were going to die, I'd at least want to try something new even if the chances were slim. If it didn't work out, at least it'd be a new data point for those that come after. That means something.
True. But speeding up the search for a treatment saves many future people.
The ethical tradeoff between definitely saving a life now or probably saving many lives later is an age old problem, but one which society hasn't properly converted into laws and processes in medicine.
> A simple way to stem most snake oil is to put all payments for snake oil treatments into escrow till the treatment is approved.
I doubt any company anywhere (legitimate or not) would provide drugs under such conditions. It would make much more sense to just focus on getting approval instead.
It should be a escrow release when a patient is cured.
This just winds up being cruel. We don't understand a number of diseases, and we don't know how to cure them.
But we can treat symptoms, and sometimes prevent them even if it isn't a cure. It's OK to make Insulin Plus that keeps diabetics alive longer. I have MS, and freaking trust me, I want my non-cure medicine. Without that medicine, my chances of having a very poor quality of life full of discomfort increases pretty dramatically. Lots of things are like this: No real cure, but we make folks lives better by treating symptoms or preventing some damage and things like that.
The only way to not be cruel is to give treatments that work even if they aren't a cure.
Symptoms are used to diagnose, ergo is a treatment of symptoms a cure?
Lets not forget the expansion of the DSM which pretty much incorporates every human being as having a mental health issue or sexual deviancy fetish.
There is no normal in the DSM, so would some medical experts start dialling back on diagnosing new conditions to pad out their careers and income?
That bit about the DSM is a pretty obvious layperson's point of view: It is easy to say that you fit the criteria when you forget that the symptoms need to have negative consequences on your life. And there is 'normal' - normal is a range.
There is a huge difference between being down after a loved one's death and finding yourself feeling that way for no reason or not coping 2 years later.
Considering that - there is no way to answer the last question. That's just a "what if" argument and fails to take into consideration that there is a shortage of mental health experts, and there is absolutely no need for someone to do that sort of thing.
And no, no everyone has a "sexual deviancy fetish", just for the record.
As far as 'treating symptoms'... I have MS. I take medication that slows the disease. If I had fatigue or pain, they would try to treat that too. If it causes depression - which it can - they'd try to treat that. No matter what treatments I get for symptoms, I still have the disease. There is no actual cure.
> That bit about the DSM is a pretty obvious layperson's point of view: It is easy to say that you fit the criteria when you forget that the symptoms need to have negative consequences on your life. And there is 'normal' - normal is a range.
Define normal? Likewise considering the all encompassing vagaries of some words, as noted in legislation, and the lack of detail that exists in descriptions of diagnosis and symptoms, whilst this makes it easier to generate AI's to replace some experts, its not really helping the patient is it?
>And no, no everyone has a "sexual deviancy fetish", just for the record.
Define normal.
> There is no actual cure.
You are uniquely placed to actually find a cure, because I'm reminded of how tolerant (lab) animals are when level 1 of maslows heirachy of needs exists, and I'm also reminded that (lab) animals can not convey information that an owner of a pet or intelligently constructed lab experiment could elucidate.
The phrase "Dont take no for answer" springs to mind, and Thomas Pynchon "If they can get you asking the wrong questions, they don't have to worry about answers.".
Survival of the fittest comes in all shapes and form. I know that copious amounts of histidine a precursor to histamine also causes remyelination of the nervous system, so maybe you have an amino acid lead that might be worth investigating.
There's a trivial well-regulated market solution: medical company A registers treatment B with the FDA; patients can try experimental B from A on A's dime: let them out their money where their medicine is.
Exactly, a treatment should be free until approved by FDA.
The team would try to make the treatment an experiment useful for science. They would have no incentives to kill prematurely patients that would otherwise have lived longer. They would work in good faith.
Disclaimer: I actually had had a treatment (surgery) not yet approved, it saved my foot from amputation. This was in Europe.
The doctor was adding me to the long lists of patients he saved. He also trained other doctors to perform the surgery. Eventually the procedure was approved by FDA and in Europe. I'm glad to have contributed.
Before going on that I read all the articles related to my problem (many thanks to sci-hub) and then send a email to the surgeon. He said "I can indeed help you" (best day of my life) I didn't pay anything (only the plane tickets to get where he was)
Before approval it's research, it's an investment. When in developing phase it's normal not to make money.
After approval it's the health insurance or the patient that pay. In countries like Singapore or France the taxes pay so it's "free" (actually it's an "insurance" backed by the govt)
Steve Jobs got into alternative medicine to treat his pancreatic cancer, including trying a fruitarian diet. Since he had a rare form that isn’t as fatal as pancreatic cancer usually is, there’s a chance he could have survived significantly longer if he had instead treated it with traditional, non-experimental medicine.
Maybe someone should create a throwaway and provide a list of they’re concerned about retribution. People not calling out scum because they are afraid of the consequences of outing criminals makes the world a crappier place for everyone.
Let's just say I have a personal blacklist of therapeutics companies I will NEVER seriously work for (though I have done a couple things for them that satisfied my conscience), and a few electrical schematics squirreled away should I need to defend myself someday....
Id let people use unaprooved treatments labeling them with big warnings in red that this is not approved and may be snakeoil or something like that. Whoever attempts to hide, remove such labels fined severely, possible jail time. Couple of scandals of unaprooved treatments wreaking havok and very few would risk it afterwards.
> 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.
You say this now, but after your son, sister or mother dies after choosing snake oil, you will likely not say "I accept that they chose wrong and that's all there is to it". You will cry bloody murder and blame the system that didn't protect them from the snake oil salesmen, and demand that something be done.
Well, I of course don't know what you personally would do. But some people would do this, and it turns out, actually a lot of the people in that situation would do that. And so something gets done.
This is the same thing as crypto, people "reserving the right to take risks with their own money", and after the money is lost asking why the government didn't protect them. And the same as many other things. Humans suck at accepting the consequences of their own choices.
Nobody has a fetish of taking your choice away from you. People ask for things to be this way, because people are just human.
I agree with your description of reality. That doesn't mean that we have to accept it or say it's ok. It may be politically infeasible for the suggested policy (allowing people to choose treatments even if some people _will_ choose unwisely), or, if enacted, it may be impossible to keep it. But I will continue to advocate for it anyways. I believe in and advocate for _many_ policies that I have close to zero hope will ever be enacted.
IMHO, the solution is not advocacy for policies where people get to choose and take the risk and get whatever results they get. Because there will generally be more people advocating for forced "good" choices.
The solution, I think, is to teach people to understand risk, choices and consequences better. With enough teaching, maybe the advocacy for the forced good will decrease.
I share the same mindset as u and I’ve been told countless times something to the effect of “yea but that’s not realistic” yet I never stop. I’ve often wondered why that is; I assume it’s just some psychological thing/on principle of not simply accepting this thing I perceive as stupid.
Additionally, I think it’s partly me just wanting to spread awareness about <stupid thing> and possibly engage smarter people than me to devise better resolutions/implementations as well.
Wondering if u have any thoughts or I’m just galaxy braining it
Let's say a treatment kills 9 out of 10 people. Maybe those 9 were terminally ill & that's why they died, but maybe the company was just lying and their treatment was doing nothing or killing people more quickly. How do you determine that? When would you shutdown a "death factory"? Would you require mandatory disclosures of the death rate & risks, or could a company hide those facts from prospective patients, only talking about the patients who survived? If they can't show efficacy, should they still be allowed to sell to patients?
I think the ideal of regulation is to try to remove the guesswork & expertise required for the end user to do due diligence. It's not perfect, but at least some minimum level of regulation, such as mandatory efficacy disclosures, would be needed.
I don't fundamentally disagree with you, I just understand why, as a society we may choose a different thing.
One of the reasons my father died of cancer quickly is that he was convinced by a chiropractor/osteopath that he had trouble with his back which could be cured with manipulation.
He was not an idiot, but sick people will make bad choices.
The abstract world of "either I die or I try this experimental treatment" is far more blurry, and there lies the problem, in my very humble opinion.
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.
And how do we assess whether "someone understands the risk"? Often, I suspect nobody really "understands" the risk of some minimally-tested, experimental treatment.
Yes, I suppose it could be taken that way. I wasn't intending to argue one way or the other, merely to point out that such an apparently simple condition ("if someone understands...") actually encompasses a huge amount of uncertainty, and so doesn't necessarily represent the "easy answer" that it might at first appear.
Which why in a lot of instances in our lives we are not allowed full personal autonomy. We try to minimize collateral damage as well as self-damage to some extent.
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.
Imminotherapies very quickly kill a significant percentage of the people who try them. So it’s a complicated balancing act when someone is likely to die in say 1-2 years but also likely to survive another 6 months.
For people who are likely to die very soon the case is more clear cut, but the people developing these treatments don’t have the resources or infrastructure to try and treat more than a tiny handful of people. Allowing people to pay for such treatments also opens the door for a huge range of bad actors which also costs lives. I am not saying the current system is great, just that there’s a lot more complexity than is obvious on the surface.
I have a good friend who went through Immunotherapy on a Stage 4 lung cancer and had an impressive recovery (all the metastasis tumours disappeared in the scan pictures I've seen). Not cured of course, but has a much longer life expectancy. So I've seen at least one anecdotal evidence that they work.
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.
My friends mom bought a fancy light for 2000€ that was supposed to cure her cancer. Spoiler: it did not.
Now, that wasn't in the US, and I'm pretty sure the quack device wasn't approved as a medical device. But the fact is that fraudsters will sell their fake medical products to desperate patients who have nothing left to try. These people should rot in jail.
My idea is not about quack medicine. People should be discouraged from using quack medicine, and made abundantly informed that it's guaranteed not to work, while consuming their precious time alive which other treatments might extend.
My idea is about something that has promising results in scientific trials, but may carry unknown risks, and so is not yet approved. The risks may be worth it, because the alternative is a certain and quick death.
The patients should, of course, be also abundantly informed about the risks, the odds of success, etc.
Of course, some people would do things that we would find irrational, no matter how we try to persuade them against that. This may of course be painful to see, but I don't see why should we curtail the free will of an adult in their sane mind, as long as nobody's rights are being infringed. Certain new things always look crazy even though they have merit: see vaccines, blood transfusion, etc.
It’s unfair to call treatments untested. Medications are tested extensively. The FDA could work with sponsors to come up with a range of risk profiles and expand access.
I don't have an issue with people taking magic beans to heal themselves; it's the sellers who knowingly (whole other kettle of fish there) sell snake-oil that are the immoral ones.
If the treatment needs to be administrated by a doctor, it demands the resources of the hospital and connected system, for a novel process. It does introduce a real risk factor for the rest of the healthcare provider’s system and the other people counting on it. I don’t see the comparison you’re making at all, really - a novel treatment has completely different context from an abortion.
Talking about immunotherapies feels like oh yes of course it would be worth it…but should you also be able to print out a blog article about holistic medicine and demand the hospital follow that treatment plan for your illness? Should a person insisting their illness be treated with an untested therapy from a disreputable company get a hospital bed instead of you for the same condition because they arrived first?
IMO this seems like something where the burden on the medical system is at least as much of a factor as the risk to the patient.
It took about 40 years to find efficient ways to treat AIDS.
It took about one year to find efficient ways to treat COVID-19.
So, if you have a condition with a few years of life expectancy remaining, maybe it's worth it to wait for some promising scientific results to turn into an approved medicine that will cure you. If you have a few decades (e.g. the normal life expectancy), even more so. If you doctors give you a few months though, maybe the "try anything" approach is a better gamble.
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?
Your guilty conscience will undoubtedly destroy you from within. If you do not repent and request mercy from the great beyonder then surely your next life will be lived in misery as some sort of atomic particle with human awareness and deep dread of your current circumstances.
I can't tell how much of your sarcasm is based on taking me literally. I'm an atheist. I don't believe in an afterlife, and I'm always blown away when people say that without a "fear of God" or fear of hell, no one would act morally. Whenever someone says that, I'm like, well, I guess you want to kill and torture and rape people and you need this dumb framework to stop you from doing that, so thank goodness for religion. But personally I think we all have ethical responsibilities to other living beings, and especially to our own kind, which spring from appreciating the complexity of the world but can be completely attributed to rational, selfish, deductive reasoning and self-preservation, if you really want to get down to it.
Tl;dr you're arguing the fundamentalist POV that ethics can't exist without a God.
It interprets telling the vehicle to crash into a barrier rather than hit pedestrians as not placing as much value on protecting passengers. But really, this is just a recognition that the passengers are far more protected in a crash than the pedestrian are when getting hit by the car. Instead of a barrier, it should be a large cliff or something.
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.
There's a lot of problems with it, though. Even if advancing medical research was the main goal-- ad hoc use in dying patients provides unclear data. Medical research wants clear inclusion criteria, metrics, reduced statistical noise from similar patients, predeclared outcome measures, and economies of scale in running trials.
We already let terminal patients participate in medical research, but only inviting patients at times and meeting criteria that optimizes the research. Also, only where IRBs have found it to be ethical-- this means not replacing a drug with proven benefit with an experimental treatment with unknown benefit recklessly.
But terminally-ill patients push for inclusion beyond this: to be dosed when there is not an active trial, or to be dosed when they are so sick that the outcome would be difficult to interpret or compare, etc. This isn't for medical research, this is for self-preservation.
>There's a lot of problems with it, though. [...] Medical research wants clear inclusion criteria, [...] , but only inviting patients at times and meeting criteria that optimizes the research [...] But terminally-ill patients push for inclusion beyond this: to be dosed when there is not an active trial, [...]
Your objections are sensible but that's beyond the scope of this author's argument. I'm just taking author's following comment at face value:
">The FDA was loathe to approve initial mRNA human trials, even when those trials would have been full of people like me: those who are facing death sentences anyway."
If it's the drug researchers who don't want the author as a test subject, that's understandable. But he's arguing the _FDA_ shouldn't be the one blocking his participation.
For the situations where there's "no active trial" caused by the FDA not greenlighting the experiments, then of course, the complaint will be that "terminally ill patients want to participate in trials that don't exist". That's sort of a circular argument -- caused by the FDA.
Again, if there's no active trial because the medical researchers themselves are not yet ready, that's understandable. But if the drug scientists are ready but the FDA is not, that's a different issue and it's the focus of the author's essay.
All that said, I don't know how much scientific progress the FDA holds back because of "safety". I'm just trying to explain the author's position.
> I'm just taking author's following comment at face value
Plenty of mRNA human trials of cancer treatment are in progress. Indeed, as he stated, he wants into two that are underway, but that he is probably too far along for. He wishes that they had been greenlit even earlier and perhaps made their way to be approved drugs that he could just be given by his local doctor.
> For the situations where there's "no active trial" caused by the FDA not greenlighting the experiments,
There's compassionate use exceptions for circumstances like this.
The big thing is, there's two big bars to cross with getting a trial together:
- You probably want to be doing human research in a way that will produce evidence that will convince the FDA to grant you approval. (Hence, drug companies often are nervous that compassionate use will pollute their data).
- The FDA wants to protect human subjects, and if there's a drug that results in 15% survival for a year, vs. 5% for doing nothing and ???% for your new experimental treatment: they want that drug to be tested as part of a protocol that minimizes potential harms, not to randomly replace the 15% survival treatment. Most experimental treatments end up failing.
> Indeed, as he stated, he wants into two that are underway, but that he is probably too far along for.
The author is incorrect on this, he’s not too far along but he does not meet inclusion criteria for either of the studies he cited as both require systemic therapy.
mRNA is not being pitched or tested as a first-line mono therapy by Moderna. I’m not sure why the author is jumping the gun here and ignoring approved systemic treatment options.
I’m ignoring that part because it is nearly impossible to prognosticate prior to initiation of systemic therapy, with the exception of some phenotypes but we don’t have the pathology report in this case.
My point is that he doesn’t even meet the inclusion criteria for these studies, regardless of aggressiveness. This has nothing to do with the FDA, he can’t join the studies because Moderna doesn’t want to study him at this point and not because he won’t survive long enough to enroll.
Whether or not his prognosis statement is correct.
Excellent explanation, parent is also correct. I think the author’s position is misinformed.
The FDA doesn’t hold back researchers on inclusion/exclusion criteria.
Inclusion for the Moderna trial he linked to:
> Must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments. Primary refractory is defined as prior exposure to anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibody for at least 6 weeks but no more than 6 months with demonstration of progression on 2 separate scans at least 4 weeks apart but no more than 12 weeks apart and progression occurring within 6 months after first dose of anti-PD-1 antibody. Acquired secondary resistance must have confirmed objective response or prolonged stable disease (SD) (>6 months), followed by disease progression in the setting of ongoing treatment and confirmed progression on scans at least 4 weeks apart.
Exclusion criteria:
> Participant has received treatment with prohibited medications (that is, concurrent anticancer therapy including other chemotherapy, radiation [local radiation for palliative care is permitted with approval from the Sponsor]…
From the description of the patient’s treatment course it sounds like he had curative intent radiation (given he subsequently had surgery) and would probably not meet this study’s criteria making the limiting factor Moderna not the FDA.
He also doesn’t mention whether he’s starting immunotherapy/checkpoint inhibitors (or his tumor status) and may be lumping immunotherapy with chemotherapy which is a good new treatment option and would typically be offered if eligible. Definitely better than being enrolled in a dose study and in fact is required by Moderna.
> 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.
> The incentive isn't to cure but to treat. The Market wants (repeat) customers.
I am fed up with this argument.
Compared to a recurring treatment, a cure will:
- destroy the competing recurring treatment
- sell particularly well initially, when you still have the patent, potentially at a high price
- not stop the influx of repeat customers, since as long as people are alive, they will need medicine, and people who are now healthy because you cured them will be more likely to have a well paying job that will pay for expensive drugs
If that argument was true, no one would do vaccines, especially considering that most vaccines are not particularly expensive.
> Yee, though, says Gilead isn't filling a hole left from its declining HCV unit. It's merely coming down off a "massive bolus of hundreds of thousands of people who came in during the first two years."
> "The drug is still set to do $8 billion in 2017 and is one of the largest drugs in the world. Not exactly a hole," he said.
The Gilead stock is worth 4x today what it was worth in 2012, before they had the cure. It is better than the average "big-pharma" (ex: Pfizer). The stock plateaued because they couldn't follow up, but before you look at the dip, you should look at the massive raise before it.
Wall Street dinged them because Gilead is a one trick pony and the street overestimated revenue, not because Gilead cured HCV rather than just treating it.
Additionally, if their drug didn’t work as well they wouldn’t have gotten away with charging 100k for a course and wouldn’t have made 40B+ in revenue.
Agree. I can speak for oncology where the desire is always curative intent treatments. Unfortunately it’s often not possible so we settle for palliative therapy (presumably what GP meant by recurring).
Personally/professionally I think this argument comes from non-experts failing to understand the disease process and therapeutic challenges. I’ve seen no evidence or suggestion in my years of clinical practice that this assertion has a shred of truth behind it.
> If that argument was true, no one would do vaccines, especially considering that most vaccines are not particularly expensive.
While I agree with you this statement does not prove your argument. Vaccines aren’t a good example of funding for curative intent treatments.
The economics behind vaccinations are different as you vaccinate orders of magnitude more patients than would ever get the disease so even if the nefarious assumption is valid the economics may still favor this path.
This example is poorly chosen for a different reason explained in my comment.
Alternatively, we can look at novel curative intent therapies for cancer like focal ablation or stereotactic radiation.
The recurring customer alternative of chemo/immunotherapy or the conventional surgical option are at least an order of magnitude more expensive.
You won’t find much novel systemic therapy that’s curative intent because it’s really hard (?impossible) to do, not because the system wants to make more money slowly killing patients.
Indeed, there's the perverse insensitive to create a repeat customer.
Funnily, an insurance company would push against that, for a final cure. They would like to avoid to pay for repeat treatments.
But the medical insurance in the US is more of a payment scheme, and apparently is not interested in paying less. I bet there is some regulatory loophole, or a government guarantee, that makes it more profitable.
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.
We let people have assisted-suicide for reasons from homelessness to hearing loss, twenty thousand people a year. Why do we respect their self-ownership when they're trying to die but not when they're trying not to die? Why do we get to decide what is and isn't worth the risk?
> Why do we get to decide what is and isn't worth the risk?
It's not their risk to take. Getting a drug to market is a complex process that can be derailed by any number of mistakes ranging from the mundane like improper blood draw during clinical trials to the tragic like accidental deaths that puts public pressure on the FDA to shut it down or spook away investors. Any hiccup in this process can kill it and once a patent expires, the chances of someone bringing that drug to market is almost zero, regardless of its efficacy.
The vast majority of drugs and therapies are developed via private investment and many companies go public before they make even a cent of revenue to fund the clinical trials. Public sentiment is the driving force behind their stock prices because they're literally forbidden from making money until the FDA approves their drug. Lots of them go bankrupt every year before finishing clinical trials or releasing a product and rushing the process is quick ticket there.
Patients don't get to put at risk the decades of good a drug can do because they're desperate and afraid of dying.
I'm not sure removing options from the desperate and dying is a good idea. Those with means will just ignore your concerns and the rest will have _nothing to lose_.
I can't find it anymore, but there was a paper or maybe study looking into the question of healthcare outcomes for just such "people of means." Iirc there was some interesting data which showed being able to afford doctor shopping and concierge service was sometimes correlated with poor outcomes compared to the standard of care overall. I think it makes sense, the patient can demand what they want and then get it, but they're not necessarily armed with the knowledge or perspective to make the informed decision. If they can afford to find a doctor who values a lot of money over anything else though, they can get it, and that might not work out so well for them.
Michael Jackson, Joan Rivers and Lisa-Marie Presley for example would probably all still be alive if they didn't have the money to simply buy the healthcare they wanted, damn the consequences and cost.
Because they're trying to die, they're literally getting what they want, guaranteed. Having said that I don't agree with assisted suicide for the reasons you listed. Either way it's not as though people seeking death are being mislead as to the odds, are engaging in desperate reasoning that they'll be the lucky ones who get to live a bit longer.
You offer someone death, they get death.
This is about people desperate for cures and treatments that probably won't work, and may well give them the opposite outcome from what they hope for.
Either way it's not as though people seeking death are being mislead as to the odds, are engaging in desperate reasoning that they'll be the lucky ones who get to live a bit longer
This applies just as much to approved treatments as unapproved, for the same reasons, and has the exact same solutions such as having a third party with no vested interests explain to the patient. In fact it has those problems less than approved treatments because the companies are being paid by the insurance company for the approved treatments but not the experimental ones.
The key is that the approved treatments are proven to have the requisite efficacy, the risks that come with that are an acceptable tradeoff. The unapproved, often largely untested world of early breakthroughs doesn't have that guarantee of potential efficacy, it often JUST has risks.
It may help to not view the options as a binary choice between drugs approved under the current process and any drug not currently approved.
What constitutes the acceptable tradeoff is the heart of the matter. On the one hand, even the current approval process does not always guarantee efficacy (Aduhelm to mention it by name). Medical trials work with considerable uncertainty, and the risk/benefit tradeoff is always a question of probabilities. Even with the current process, there is no certainty or guarantee.
It is possible to take those probabilities and to talk about the expected number needed to treat (NNT) for a medication, the expected side effect profile, how many people might live and how many might die. Things that may sound cold, but that are already routinely done today.
It is hard to know where the tradeoff should be, how much margin of error is the right amount before something is approved, knowing that there is uncertainty even in large trials, but it's not a choice between the totally unapproved and the status quo. (Better yet, we should not model the choice as a single parameter that goes from more choice & more snake oil to less choice & more safety. It's also often possible to improve one aspect of a bureaucracy without it being a zero-sum game.)
I don’t understand your overall point here as this is pretty much how the current system works.
> It is possible to take those probabilities and to talk about the expected number needed to treat (NNT) for a medication, the expected side effect profile, how many people might live and how many might die.
NNT > NNH = efficacy. To calculate these the trials need to be done, which is not the case for experimental therapies as they have undetermined benefits and harms (hence why they’re in trial).
The choice here is between conventional options that have known benefits/harms, however crappy they may be, with something that has unknown values.
Trials are done in multiple phases, with a progressively wider population. There is a point where we consider a drug to still be unproven, but safe enough for human trials.
I think that situations like TFA make a compelling case for selectively broadening access, for some drugs and some pathologies. The characterization of a choice between something proven and something with unknown values is too coarse and not a good model.
Clinical trials are very expensive, drug development as a field tends to move forward with what it thinks will have a chance of making it through. While most new drugs indeed fail (the large majority of them), in diseases with very poor prognosis like OP's cancer, I think we would benefit from still looking at the tradeoff as a decision under uncertainty, instead of a complete unknown. Even with less data than we would otherwise want.
Looking at experimental therapies as completely undetermined leads to a binary choice. There is supporting evidence that allows those therapies to move forward with experimental trials in the first place. The counterfactual of not treating patients with poor prognosis being what it is, my overall point is that treating experimental drugs as total unknowns with benefits and harms that cannot be quantified until the full process is finished is not consistent with the knowledge that, even after all trials are completed, this is still a uncertain statistical result, only with slightly more data than before.
In other words, we are always working with partial unknowns so when the prognosis is bad a larger unknown may be good overall and save lives, even though it wouldn't be acceptable otherwise.
> While most new drugs indeed fail (the large majority of them), in diseases with very poor prognosis like OP's cancer, I think we would benefit from still looking at the tradeoff as a decision under uncertainty, instead of a complete unknown. Even with less data than we would otherwise want.
Which is literally what just happened with osimertinib for NSCLC. It was approved for clinical use and was implemented without any overall survival data.
Safe for clinical trial means the harms are considered safe, has little to no relevance for efficacy.
Once again you’re ignoring the fact that there are (almost) always alternative treatments that have been proven to prolong life.
No one is offering nothing to poor prognosis patients.
From the blog post:
> Monday I’m starting chemotherapy, but that’s almost certainly going to fail, because a CT scan shows four to six new gross tumors, four in my neck and two, possibly, in my lungs.
In someone with such an aggressive disease everything is almost certainly going to fail, experimental or not. Chemotherapy will buy some time. Who knows what an mRNA treatment will do but there’s certainly no (not little, no) evidence that it will be curative.
You're right that there are alternatives, and there is an existing standard of care. I don't think I'm ignoring that. Let me clarify, I am not saying that patients with poor prognosis are being offered nothing. They are being offered standard of care.
I think sticking with standard of care until new drugs have gone through the full, current process may be net negative under the current process, and considering the counterfactual especially for patients with poor prognosis.
Chemoterapy will buy some time with certainty, but in expectations broadening access even slightly means we can gain confidence in the experimental treatments that do work slightly sooner, and that improves the standard of care for everyone. Experimental drugs sometimes do work, and it would be bias to only look at the risks while sweeping aside the potential upside.
Consider what happens a few years from now with the current system and with a system that selectively broadens access in some cases, when the early data seems to support the risk/reward. Even if most new medications fail, the cost of delaying those few therapy that will happen to work is much larger than the risk being paid by the trial population. That's because only a few people participate in trials, but everyone benefits from the results. This is why we have trials at all.
In someone with an aggressive disease such as OP, that person may very likely benefit from having that choice. Today they may choose to buy some time with _relative_ certainty, knowing that chemo has very heavy side effects and that they may not enjoy very much of that remaining time. But they may not choose to try some experimental treatments, even when the risk/reward seems reasonable according to early data, even though that may result in a small chance of success, and certainly data that will help bring therapies quicker to more people.
The benefit of experimental treatment is not just to the individual participating in the experiment. Part of the benefit, that helps justifies the risk, is the idea that a fraction of the treatments will be worthwhile. Slowing down trials is safer in the sense that no one will be responsible for anyone losing their chance at chemo or dying, but it creates the exact kind of invisible deaths in expectation that TFA talks about.
Current standard of care includes experimental therapy. What you are describing is once again how novel cancer treatments are being implemented today.
Furthermore, Step 1 of the NCCN treatment guidelines for these kinds of cancers (i.e. advanced and/or poor responders to conventional chemo) is always that the patient is enrolled in a clinical trial.
In this authors case he does not meet inclusion criteria for the therapies he is listing, both trials require systemic therapy with novel PD-1 inhibitors (aka immune checkpoint inhibitors, immunotherapy) which when they work do so fantastically with little side effects.
Per his description he has not tried any systemic therapy yet.
I’m unclear whether he’s lumping chemo with immunotherapy (often the case by non-domain expert patients) but not even Moderna is interested in going from surgery directly to mRNA.
This isn’t the FDA getting in the way. He hasn’t exhausted good treatment options yet to be eligible for unapproved experimental ones. It would absolutely be detrimental to ignore ICIs in an eligible patient in favor of [insert non-approved experimental therapy with no evidence].
I’ve seen far more advanced metastatic H&N SCC survive for years on ICIs in my clinical practice. We don’t know all the specifics of this case but this isn’t nothing/days/weeks vs mRNA as the author is pitching.
That's fair, I'll admit I didn't check the inclusion criteria in the case of OP.
I'll take your point, and I appreciate the time you took to write a good response, though I've read about enough examples other than the current article that I feel this may be rejecting a wider pattern on the details of the current submission (but maybe I'm wrong, and they all happened to be incorrect for similar reasons).
But I'd like to hear your thoughts on the broader argument of being more aggressive with trials in general. What sticks with me each time this argument comes up, regardless of the particular situation, is this idea that despite some mechanisms for accelerated approvals, we are still far slower than we could be, if we take into account the number of people saved by bringing therapies sooner.
There is a cost to letting people take dangerous medication. I hate the idea of peddling dubious cures to vulnerable people as much as I'm sure you do. It's the counterfactual that makes the argument, the people who do not receive treatment due to delay seems to vastly outnumber the people harmed by experimental treatments.
And the difference seems large enough that it would remain true even if we went much faster. I think that's the strongest objection to the current system.
Please note I am speaking only for the world of oncology as that's my practice focus and what I know best.
> But I'd like to hear your thoughts on the broader argument of being more aggressive with trials in general. What sticks with me each time this argument comes up, regardless of the particular situation, is this idea that despite some mechanisms for accelerated approvals, we are still far slower than we could be, if we take into account the number of people saved by bringing therapies sooner.
Everything in medicine is trade-off. On the extremes we can practice with no regulation and have immediate access to treatments without evidence accepting that many patients will be harmed as many new treatments are inferior or require phase IIIs on the other end and minimize harms but accept that delayed care will itself cause harm.
Current practice is somewhere in the middle, depending on various factors like efficacy, risks/harms, and alternatives many treatments enter practice after phase I/II or used off-label for close indications.
I like where we're currently at for oncology and don't think we need to change much in the process. The bigger hurdle is funneling those R&D $ into high yield research and perhaps making the cost of trials easier (e.g. research alliances, IT infrastructure to simplify multi-center studies and patient recruitment, ?active government involvement).
There's always fine tuning of that balance that can be done and some cases will prove things wrong on either side of the argument but generally speaking I think we're close to where we need to be. Definitely better than when we didn't have the current approval process.
> It's the counterfactual that makes the argument, the people who do not receive treatment due to delay seems to vastly outnumber the people harmed by experimental treatments.
I don't think this is true and I have not seen evidence to support this claim. There is ample evidence of failed treatment options or treatment causing more harm than good. An example I'm well-versed in is HIPEC for advanced ovarian/peritoneal cancers (we've been doing this for years and it turns out it doesn't do much other than excessive morbidity) or Y-90 for HCC/colorectal metastases to the liver (first trials negative and we recently found out "oops we've been underdosing this and measuring non-target dosing to the lungs incorrectly") both of which are for palliative patients with no good alternatives.
Going back to osimertinib as the example, the main criticism of earlier TKIs (same class of drug, and even osimertinib for that matter) was that the promise of limited data (progression free survival rather than overall) led some patients to get TKI therapy rather than platinum based chemo which was standard of care and has proven OS benefit. Except when the OS data came out it was an "oops, OS didn't pan out like PFS" and people were harmed.
That these happen in the current system strongly suggest patients have access to experimental therapies and that we're not being overly stringent, or this data wouldn't exist.
I would also say that a large proportion of the patients I've interacted with that have disseminated disease are on some trial for experimental therapy with the caveat that I've only worked at tertiary care cancer centers. It's really not that hard to get enrolled if you meet criteria. I believe the stories we read of access challenges are largely a vocal minority with challenging circumstances or a misunderstanding of treatment options.
No problem. I appreciate the discussion, it's good for me (and medicine in general) to be challenged on held beliefs as things tend to devolve insidiously in this field.
Did you never experience the situation where someone you care about is making a choice you think is wrong, and you want to protect them from themselves?
I'm not saying this is the right thing to do. I'm just trying to explain how it happens. People don't make good risk judgements in general, and other people think that it is good to do good by force. This is why seat belts are mandatory, smoking is discouraged, drugs are illegal, public companies traded on exchanges are strongly regulated, and so on and so forth.
> Yes probably more people will die
You really don't understand why we choose the option where less people die? We value life, I guess.
The COVID vaccine already had an existing model to work from that was already ready to go and approved in the SARS-COV-1 vaccine nearly a decade earlier.
> 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.
> Most drugs fail. But getting the drugs that do work to patients even a year earlier may be a much larger benefit than the cost of giving people with serious diseases broader choices, in addition to the current best known standard.
This is contradictory. Most drugs fail, how do we identify the efficacious ones other than through trials?
Depending on the anticipated efficacy from early trials as compared to existing ones it will get fast-tracked before the phase II is completed.
Where is the evidence that we’re delaying efficacious therapies where there is no good alternative?
I sound like a broken record right now but this blog post is suggesting we jump to experimental therapies (which would be off label for the author as he does not meet inclusion criteria) before we even have phase I data let alone efficacy, when good validated treatment options exists.
>This is contradictory. Most drugs fail, how do we identify the efficacious ones other than through trials?
One idea is to make trials somewhat less costly by relying more on post-approval monitoring, but there are more subtle critiques of the processes that try to address perceived inefficiencies at the organisation/bureaucratic level rather than just adjusting a single big strict/lenient dial.
Some drugs do not make it to trial at all due to the overwhelming cost of the process. We would identify a larger number of efficacious ones if there were less costly, wider trials. A very expensive approval process results in delays for drugs that do make it to trials, but also causes many candidates to never reach trials.
>Depending on the anticipated efficacy from early trials as compared to existing ones it will get fast-tracked before the phase II is completed.
Part of the argument is that this is good, and we should consider going further in that direction
>Where is the evidence that we’re delaying efficacious therapies where there is no good alternative?
Unfortunately, the best I can point to is a series of blog posts and informal discussions, I'm not aware of any formal published evidence. I remember a blog post on ACX post aducanumab (https://astralcodexten.substack.com/p/adumbrations-of-aducan...). The "FDA delenda est" catchprase leads to several more posts.
I'll admit this is not very compelling. I believe it's worth having that argument, and I'd be happy to be wrong on that one, but all of this is hard to quantify.
(I also want to reaffirm that there are good alternatives, it's a question of whether we could be losing less people than we are losing under the current process, not that there are no current alternatives)
>I sound like a broken record right now but this blog post is suggesting we jump to experimental therapies (which would be off label for the author as he does not meet inclusion criteria) before we even have phase I data let alone efficacy, when good validated treatment options exists.
I'm sorry if I'm repeating myself as well or failing to make a good argument. I think your position is very reasonable. It's a complicated topic and I might not be doing it justice.
> Unfortunately, the best I can point to is a series of blog posts and informal discussions, I'm not aware of any formal published evidence. I remember a blog post on ACX post aducanumab (https://astralcodexten.substack.com/p/adumbrations-of-aducan...). The "FDA delenda est" catchprase leads to several more posts.
I'm a radiologist by training with an interventional oncology component in my practice so I can really only speak to acute care emergencies and cancer with any degree of expertise.
Cancer, heart attacks, strokes, aneurysms are different because there's a time crunch. In these situations FDA approval comes quickly for new medical devices and imaging tests. New aneurysms occlusion devices, stent grafts, and thrombectomy devices are all quickly approved with shortened review processes. Sometimes this has been to our detriment (e.g. early abdominal aortic/EVAR grafts which all leaked and caused disasters when the patient needed re-operation).
In these cases we did exactly what you're suggesting with:
> One idea is to make trials somewhat less costly by relying more on post-approval monitoring
How this translates to other diseases like Alzheimer's is not in my wheelhouse. I assume the process is more strictly adhered to in these cases, but it presumably should be because the potential harm of delaying is seemingly less important unless we're discussing disease-modifying treatments that require early initiation.
In your post the author mentions COVID-19 vaccinations, these were made available before full FDA approval. COVID-19 was highly politicized and the entire process did not follow typical medical procedures. Honestly the evidence that has come out for them isn't very compelling (omicron and later) and largely why most places have dropped vaccination requirements. I'm not sure that this is a good example of the "FDA's failure".
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.
Thanks, very interesting.. i dont know if it's worth setting up a group to raise statistical understanding or just wait for society to suffer enough to finally learn.
> 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.
you’re right though, I think this is still limiting as it gets to currently obscure things, liability concerns for the physician if something goes wrong, or what insurance will cover. so its still hit or miss for the patient
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.
> Patients generally do not have to pay extra out-of-pocket costs for treatments studied as part of a trial. Every trial is different, but the clinical trial’s sponsor usually pays for all research-related costs and any special testing.
> Typically, the patient or his or her insurance company is asked to pay for any routine tests, treatments, or procedures that would be required as part of standard cancer treatment. Before you join a clinical trial, you will receive an informed consent document that spells out exactly what you’ll have to pay for and what you won’t.
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.
A large data set of highly biased, uncontrolled data is still useless. You can't model yourself out of the factors that have not been recorded. And believe me, the data you'll get on patients that try experimental medication will be very, very incomplete.
It also won't be a large dataset. How many people have squamous cell carcinoma between now and the moment of approval and are willing and wealthy enough to buy this particular medicine? 100 seems too much already.
> The mechanisms that were in place at the time did their job.
Barely, according to wikipedia.
> 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.
Thalidomide was never going to save 100,000 people. It did cause 2500 birth defects in West Germany alone, though, plus an unknown number of abortions. Given that it was legal in 46 countries, the number of people with birth defects must be well over 10,000. This drug isn't going to save 100,000 people either, certainly not in the period until admission.
> A large data set of highly biased, uncontrolled data is still useless. You can't model yourself out of the factors that have not been recorded. And believe me, the data you'll get on patients that try experimental medication will be very, very incomplete.
There are many safety issues that placebo-controlled and double-blinded studies didn't catch, but postmarketing surveillance later did. Large data sets are more powerful than you give them credit for --- and, moreover, in the real world drugs are not always used the way they are in clinical trial settings. In the real world, people skip doses, double up on doses, drink grapefruit juice, etc.
If you want a full picture of "factors that have not been recorded," you want as large a dataset as possible, as close to real world conditions as possible. It may not be as clean as you'd like, but it'll give you enough to draw every inference.
> How many people have squamous cell carcinoma between now and the moment of approval and are willing and wealthy enough to buy this particular medicine? 100 seems too much already.
When the alternative is to allow the drug to spend a decade or longer in development hell, I'll take poor data and lives potentially saved over "great data" (not really) and a pile of dead bodies.
Besides, when drugs are potentially curative, and the disease otherwise so invariably fatal, even 50 datapoints should be sufficient. This is trivial to model mathematically.
> Barely, according to wikipedia.
Oh come on. Besides, teratogenicity is now an absolutely basic component of safety tests. You don't need the FDA's failed paradigm of extensive efficacy trials to prevent "Thalidomide part II."
> Thalidomide was never going to save 100,000 people.
The exaggerated response to Thalidomide, exemplified in your first comment, has absolutely condemned more than 100,000 people.
> 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
I'm a bit concerned about my privacy but the condition is herpes virus infection of the eye. The similar condition is Thygeson's disease. The drug in question (that I could not get) is called Viroptic which for some reason helps with both conditions (despite them not being related). Thygeson's is thought to be more of an immune system issue.
So if you've been diagnosed with herpes, and anti-virals don't seem to help, maybe you don't have herpes. If you do have herpes of the eye there are good drugs approved in Europe but not in the North America (though there are likely some approved drugs in the US which will still help - it's complicated).
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.
If you think the fact that thalidomide, a deadly and basically worthless medication, being successfully blocked by the FDA is an example of a problem, then I'm a bit baffled?
If you think that regulatory bodies make mistakes - then surely you want them checking each other's work?
It's very frustrating to feel you are dying just shy of a breakthrough that can save you. I get that. And the author's contention, that they have a right as a human being to join studies that can potentially save them, is entirely reasonable.
But that's an entire universe apart from rubber stamping medications. We should not give the pharmaceutical industry that much credulity.
If pharmaceuticals have improved the length and quality of our lives, it's because they've been kept on the straight and narrow. This isn't a self regulating industry, they have a desperate base of customers and their "sales people" (doctors) are trusted implicitly - they hold a tremendous amount of power and would abuse it at the drop of a hat.
I’m saying that the FDA’s strictness cuts both ways. My beta blocker example was not a hypothetical.
Europe approved the use of beta blockers to prevent heart attacks a decade before the US. Although the FDA approved propranolol in the 1960s, and timolol for glaucoma in 1978, they didn’t approve beta blockers for prevention of second heart attacks until the 1980s. This resulted in the deaths of over 80,000 Americans. Amusingly the New York Times article about this approval brags about how many people will be helped by the previously-banned medicine.[1] Nowhere is it pointed out that so many more people could have been saved if the FDA fast-tracked drugs approved in Europe.
It seems that if the Canadian and European regulatory bodies are incompetent or too quick to approve meds, it would show up in some statistics, right? Maybe their life expectancies would be lower or they would have higher rates of certain kinds of deaths. Yet if anything, it’s the US that lags in those areas.
There are tons of examples of the FDA failing to approve things, resulting in Americans dying unnecessarily. A more recent example was Omegaven, an IV nutritional fluid.[1] The FDA took 14 years to approve it, resulting in hundreds of infant deaths. Before its approval, only a few infants at Boston Children’s Hospital managed to get it. The staff there had to get FDA approval to import the fluid from Europe for every infant they wanted to treat, resulting in a lag time of several days. Even though it was clear that Omegaven was much more effective than previous IV nutrition, the FDA’s bureaucratic hurdles prevented it from being adopted sooner.
Maybe part of the reason that the Canadian and UK drug regulators are competent, is because we haven't created a sufficiently large system of incentives to undermine them. Maybe if approving a drug in Canada got you access to the entire world, we would have a very different scenario.
A rubber stamping scheme removes redundancy from the system. Approving drugs faster sounds like a great idea, but there was a reason someone put up that fence you want to tear down, and your arguments haven't addressed it. Furthermore, the fence doesn't need razing to accomplish your goal - I don't see why advocating for the FDA to approve drugs faster should be synonymous with turning them into a rubber stamp.
No one (or at least not me) is contesting the assertion that approving drugs faster may save lives. But I don't want pharmaceutical companies to be able to undermine a single regulatory body and then be able to distribute their drugs everywhere.
There is no reason because it wasn’t a deliberate choice. Different countries created their own standards bodies and didn’t try to coordinate until later. The same thing happened with safety regulations around automobiles and aircraft. Fortunately in those cases, most countries have coordinated and manufacturers can sell the same vehicle in different countries with little extra effort. But for rare diseases with cheap treatments (such as in the case of Omegaven), nobody has the both the resources and the desire to overcome the FDA’s bureaucratic hurdles.
Again, this is a fine argument for making the FDA more effective and for coordinating with international partners, but full of holes as an argument for rubber stamping. And I still don't see why a rubber stamp serves your purposes better.
If you think the UK, European, and Canadian regulators are competent, then you must believe in the possibility of a competent regulator, right? Let's just have one of those, instead of a differently-incompetant regulator who serves as a rubber stamp.
And if we can't, then I'd rather they were too conservative than that they allowed too many drugs on the market.
At this point I don’t know what could change your mind. Your response to any criticism of the FDA or any proposed fix is to say that we need to make the FDA more competent, as if that’s not what people have been trying to do since the FDA was created. Unless you provide details about what would be different from what we’re already doing, you’re just arguing for the status quo.
It’s as if I were pointing out the uselessness of most TSA screening and someone replied that the solution is to make the TSA more competent.
I’d change my mind if there were more examples of harmful drugs in Europe or Canada that the FDA blocked in the US. The thalidomide scandal was over 60 years ago and caused around 4,000 deaths and 6,000 birth defects. You’d need a dozen thalidomide scandals to equal the FDA’s delays in approving beta blockers.
I haven't made the counterclaim to that. That's not the same as saying that the FDA should rubber stamp all European approvals.
Should doctors be able to prescribe drugs approved elsewhere? When we're talking about lifesaving treatment that isn't available in the US, yeah probably there should be some process to do that. I imagine insurance companies will make this next to impossible, but that's not a reflection on your argument, just a shitty reality.
What would convince me that the FDA should rubber stamp European drug approvals? I don't know, but it would be evidence about the structure of the pharmaceutical market and the incentives in place, not a recitation of misses by the FDA.
Your evidence they aren't approving drugs fast enough is convincing, I absolutely buy that a problem exists. But that evidence doesn't address my separate concerns.
Let's say we do go ahead and rubber stamp everything coming out of Europe. What is going to happen?
There's going to be more pressure on European regulators. How are they going to respond to it?
Possibly by being corrupted and subverted and failing open. That would be bad.
The alternative is that they becoming more careful, more plodding, they start taking into account the views of stakeholders the FDA would otherwise have represented, and the process gets gummed up anyway.
I'm sorry if I came off as like, an unreasonable FDA bootlicker or as being callous to the people dying or suffering reduced quality of life due to bureaucratic incompetence, I do think that's terrible.
If what you wanted me to agree with is that doctors should be able to get people drugs that there's excellent reason to believe are safe and effective, regardless of whether the FDA has finished approving them, then yeah, I see how that makes sense.
It used to be regarded as a miracle drug that could be used over the counter in many circumstances, and as they looked into it they discovered it just couldn't be used safely.
That they've narrowed it down to some use case is more of a testament to the thoroughness of the investigation, I'm sure there are many chemicals that could treat leprosy this just happens to be the one we understand how to manufacture and when it is safe to use.
I'm sure it's very meaningful for the people who do take it, but that is what I meant by "basically worthless."
You are obviously deeply and aggressively ignorant about pharmacology. Thalidomide is an effective immunomodulator which is prescribed for multiple conditions beyond just leprosy.
That's true, though I'll note that treatment options seem to have broadened a bit [0]. Thalidomide is effective, but suffers from cost and limited availability (in addition to the teratogenic effects).
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.
They approved one drug in under a year in a literal emergency (and it's deeply controversial that they did even that). That doesn't mean they can do that with everything that crosses their desk.
I do buy the author's assertion that people should have right to expose themselves to experimental medicines when it could save their lives though.
Let's say I give you 10 tasks. You're going to have to go back and forth with external stakeholders, and a given task will be blocked much of the time waiting for a response. So you can do each of them concurrently, but it's gunnuh take a year to do each of them.
But the next day I come to you with an 11th task. I tell you this is the only one that matters. I give you full license to blow through your budget, harass people until they get their paperwork done, whatever it takes - this is the only priority. So you get right to work, and with all the blockers cleared you get it done in 6 months.
"Great," I say, "so you can do all them that fast right? And when I come back in 6 months, all of the original 10 tasks will be done?"
But of course they won't be, because you don't have the resources you had before, the external stakeholders aren't as motivated as they were before, and instead of putting all your effort into 1 task you're going to be spreading it across 10.
The external stakeholders in the FDA are extremely motivated to get approval quickly. If this is a resource problem then the case for increasing the budget is clear.
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.
Yes, magnesium was the first thing my gp recommended me. Unfortunately, magnesium supplementation had a negligible effect on my irregular heart beats, which is a pity, as it's more of a standard medication than taurine.
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 would also like to continue in perpetuity, it's why maintain general fitness and I generally avoid some life-shortening things like smoking (though I do consume alcohol). The problem is that life in perpetuity doesn't actually happen even from treatments of even our wildest sci-fi fictions. By extending life, we merely kick the can of death down the road...
Actual immortality achieved would just push concerns to the heat death of the universe, and folks acting as Cyber-Punk Holden Karnofsky would be spilling ink about the need to invest in star-moving technology to create a big crunch. I don't mean to be trite here. The point is 10 years, 100, years, 1000 years, or 100 billion years, the dilemma is the same, because the linearity of time means any non-infinite amount of life is ultimately minuscule.
The psychological dilemma of existentialism is a challenging one, I'll fully admit that. It's one I've accepted. The benefits also exist though. It forces you to live in the moment to some extent, when others are solely focused on the future.
What you want isn't always what you get. There are a lot of people that have all kinds of urges that they know aren't going to happen. That's perfectly normal, but for so called 'rational' people that fraction that has these irrational desires is a bit strange to me. Rationally: everything dies, sooner or later, and so will you. So the way to get the most out of it is to make sure that you make every minute count.
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.
I completely agree. Ironically, the existentialist should be more concerned about general welfare, not less. There is no afterlife to set things right. We should not be surprised that ethical hedonists like Peter Singer are so concerned about animal welfare.
We suffer almost certainly because it's an evolutionary adaptive feature for us we picked up somewhere along the way. It is no surprise that the general suffering we find in developed countries, namely loneliness, is directly related to human reproduction.
Is it a generally happy or sad state of affairs? Who's to say. It's our state of affairs, and we best do what we can to make the most of it.
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?
You quoted evidence without providing any, and conflate evidence with belief. That also doesn't really add anything to the conversation.
The smart money says 'there is no afterlife, so use what you've got'. If you - or anybody else - is so sure that an afterlife exists then it would be nice to present some actual proof and absent that to admit that you're making it up or that it's hearsay.
No, I think they made that up because they fell for the exact same trap as most other religions did: a desire to explain that which they didn't know anything about. They obviously didn't do it 'just for show' so I'm not sure why you would make it seem like I was thinking that.
Religions are several thing: power structures, coping mechanisms, focal points for social functions, explanatory mechanisms, scams and stories (origin myths etc) all rolled into one. Depending on which religion you are looking at one or more of these traits may be more dominant.
Every religion lays claim to some unique knowledge and tries to explain a lot more than they can and as a result they are - to me comically - incapable of adjusting to knowledge as it became available. The result is dogma, in one form or another.
I don’t know man. How many people do you know in your immediate circle that would say that they wholeheartedly believe that we only live once?
Do you not feel like life on this planet would be very different if that was the case? It’s a really deep question and I would prefer you contemplate it if you plan on responding.
Haha, ok, seriously: any answer I give you that you don't like and I haven't contemplated enough?
It's not a deep question at all, it's super superficial: the afterlife is a ruse to keep the gullible beholden to various power structures. It's a man-made construct that requires at a minimum something extra-dimensional for which there isn't a shred of evidence. How people live if they believe or if they do not believe is entirely up to them, and if they would live in a different way if they didn't believe in an afterlife means they've bought into the lies. I'd much rather people make their decisions eyes wide open informed by an ethical framework that does not rely on fairytales or outright lies.
And yes, pretty much everybody in my immediate circle except for one believes that we live only once and that one is a catholic priest of whom that would be expected. But I can't look in his head so who knows what he really believes...
It sounds like you're not up for a discussion whatsoever. And I respect that. I just dislike when people dismiss thousands of years of history because they themselves have no inherit experience with something.
Hacker News is sometimes crazy like that. You stumble into ideas/people who present to you concepts that perhaps are too crazy to take it all at once.
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.
The consequences to their actions are that when a doctor prescribes me a medication or when I purchase one off the shelf, I have incredibly high confidence that if I follow the dosage instructions it is safe - safe now, safe in 15 years, not worth further thought on my part. That hasn't been true in most places for most of human history.
The consequences to their actions are that millions of people are saved from the consequences of consuming seemingly promising drugs such as Thalidomide: https://en.wikipedia.org/wiki/Thalidomide
I could sleep just fine knowing that some people looking only at a tiny local example while ignoring the big picture considered me the villain
To the extent that is true, I agree, they should see the positive impact of what they do as well. Your blind faith in the regulatory regime, however, is deeply undeserved. Many approved drugs prove to be dangerous and we can reasonably expect that many effective drugs never make it to market because of bureaucracy.
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.
FDA doesn’t regulate supplements as medication but food; however Federal consumer protection laws prevent making false claims.
I imagine allowing terminal non-trial participants access is more than just regulatory red-tape.
If understood one of the authors points it was that allowing non-candidates access could speed up approval. I think that is true, but that would require the same regimented process for administering the trial to ensure quality of data. The same would hold if there was an adverse event as well—patients need to be monitored closely to capture data to provide valuable to the clinical research results.
Supplements are regulated as food products as long as the manufacturer doesn't claim they treat or cure anything. The FDA allows them for the same reason they allow fudge brownies or Spam to be sold.
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.
It’s not about any one person in particular. It’s about whole communities descending into hell for what could be multiple generations.
I know that in theory we all should be free and take whatever we want, but I know that in practice this doesn’t end well.
There are good reasons to control consumption of some classes of drugs that don’t have anything to do with religion and/or fake sense of morality. Some things just mess us up too hard and especially some people who are susceptible to it for various reasons.
> 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!
Because they almost certainly can not. They almost certainly have no idea what the consequences of their actions are as the drug company almost certainly did everything in their power to obscure, obfuscate, and downplay the risks as literally every company is legally allowed to do.
The principle at play here is “informed consent”. Unfortunately, modern society has little interest in the “informed” part which is why it is probably not a good idea to let people imbibe untested drugs even if they are giving “consent” unless they can demonstrate they are “informed”.
Because I don't want to live in a country where desperate people can sell their lives to soulless corporations for literal cash. That's some real dystopian bullshit. At the extreme end of this spectrum is the most dangerous game, where homeless people agree to be hunted for sport. And the topic we're actually discussing is pretty damn close to that end of the spectrum.
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.
I mean, the experimental drugs are already provided free of charge to the group participating in the study. I have no idea how it would change the economics if the ones given under any kind of "right to try" were also required to be free.
As of now, "right to try" drugs are supplied by the manufacturer under whatever terms they want at their discretion.
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".
Drug policy is larger than this single man. There are trade offs with different approaches here. “There is literally nothing to lose” is simply false. Restrictions against selling whatever to dying patients is because people _will_ take advantage of them and sell snake oil. If you’re okay with that, why not just let people steal from those terminally ill?
My dad recently died. There are always new treatments being studied and some day one of those treatments might actually be able to cure people with the same disease. That day didn’t come early enough for my dad. That sucks but it doesn’t change the fact that drug policy is made for society as a whole and not only for my dad. This isn’t some conspiracy where a cold bureaucracy is letting people die. Sometimes your luck just runs out.
It literally is a conspiracy where a cold bureaucracy is letting people die. That is exactly what is happening.
You appear to think that it is worth letting people die to avoid quack doctors being able to sell them snake oil. I prefer to leave it up to the patient to decide. They are the ones with skin in the game.
Could you please stop posting unsubstantive comments and flamebait? You've unfortunately been doing it repeatedly, and we've already asked you more than once not to. It's not what this site is for, and destroys what it is for.
Giving someone Treatment X likely means they won't be pursuing Y, whether it be to avoid polypharmacy drug interactions, or simply because the patient prefers X's side effect profile to Y. Y may be the proven treatment, with worse side effects but better efficacy. Even if the doctors inform the patient "X may not work at all and may make it worse", the patient might still choose it.
"What's the harm?" you say. The problem is, without any threshold, there are countless Treatment X. Every single snake oil comes out of the woodwork.
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.