12 ms·

When dying patients want unproven drugs

103 points by jseliger 3y ago

jseliger 3y ago
In my view, patients should have a "right to try," which is part of fundamental freedom—and this is particularly true for palliative-stage patients without a route to a cure anyway. They are risking essentially nothing. The FDA is too slow and that's costing lives: https://marginalrevolution.com/marginalrevolution/2021/08/the-fda-is-still-much-too-strict.html https://marginalrevolution.com/marginalrevolution/2021/08/th.... The issue is personal for me, too, because I have a squamous cell carcinoma (SCC) recurrence in the tongue, and the treatment that is most likely to cure it is still stuck in clinical trials. In other words, there's a reasonable shot I perish because the FDA is slow, in which case I'll wind up in the "invisible graveyard" that Tabarrok discusses.
- paulpauper 3y ago
  and the treatment that is most likely to cure it is still stuck in clinical trials. it seems like you are contradicting yourself. if it's likely to cure, then that would be borne out by the trial? And then it would be rushed for approval. The vast, vast majority of clinal trials for cancer are unsuccessful. A 'successful' drug may add a few months of life vs placebo at a cost of $10k or more per month.
  - Mattasher 3y ago
    > if it's likely to cure, then that would be borne out by the trial? And then it would be rushed for approval. I'm not sure you know how long these things take, even when they work well. Also, the failure to show a positive clinical effect in a trial mean one doesn't exist, especially at the individual level.
- seanmcdirmid 3y ago
  They had this debate in China recently and the problem was conflict of interest (lots of pricey snake oil for dying patients who can come up with the money). The market has to be regulated even for dying people, if only to prevent scams.
  - warent 3y ago
    Did the Chinese government ultimately regulate the market to protect people and prevent this kind of corruption?
    - DiscourseFan 3y ago
      The regulation is approval by a governmental agency through clinical trials
    - dspillett 3y ago
      IIRC it did, though the cynic in me would suggest that by “this kind of corruption” what it prevents is the kind of corruption that government officials don't benefit from. I trust the Chinese government less than I trust my own with regard to doing the right thing (just because it is the right thing or indeed at all), and that is a pretty low bar…
    - seanmcdirmid 3y ago
      This wiki article is probably the best place to start: https://en.m.wikipedia.org/wiki/Death_of_Wei_Zexi https://en.m.wikipedia.org/wiki/Death_of_Wei_Zexi Then there was some movement on the issue in 2019: https://www.bloomberg.com/news/features/2019-12-10/cancer-treatment-china-mulls-looser-experimental-therapy-rules https://www.bloomberg.com/news/features/2019-12-10/cancer-tr... I’m not sure where they ended up due to COVID happening next.
  - mitthrowaway2 3y ago
    Perhaps the patients should be allowed to use experimental treatments only under the condition that it is offered for free; the upside for the company is that if it works, they get the evidence of efficacy.
    - rafark 3y ago
      This should be the solution. If they’re trials for an unproven solution, why should they pay anything at all. I’m any case, it should be the other way around; it’s the companies who should pay the person for subjecting them to something very likely to be dangerous and painful. In any case, I agree with the sentiment here. People should have the right to choose.
- deleted 3y ago
  [deleted]
- jahnu 3y ago
  On this topic here is an excellent examination of it https://timharford.com/2020/06/cautionary-tales-the-spreadsheet-of-life-and-death/ https://timharford.com/2020/06/cautionary-tales-the-spreadsh...
- Veserv 3y ago
  The link you posted has a addendum which links to this: https://astralcodexten.substack.com/p/details-of-the-infant-fish-oil-story https://astralcodexten.substack.com/p/details-of-the-infant-... In the more well researched followup by the same person, the author of Astral Codex, we see that the FDA did not block or slow the approval. It was that the manufacturer had no interest in even submitting a application. In fact, the FDA regularly granted usage exemptions, granted a broad exemption for research, and even directly funded one of the first trials even though they are not primarily a funding body. The actual moral of the story maybe is that we should let third partys submit applications? It seems like there would be little risk of bad outcomes as they still need to do the approval process. It aligns incentives better as the people ultimately at risk can deploy resources comparable to their QoL improvement instead of the expected increased sales volume at current prices. There is a obvious problem that the production process is inextricably linked to the final output so a non-manufacturer has limited control and insight into a core component that introduces the possibility of regression, but it seems relatively doable to develop protocols for handling that if they do not already exist. edit: To be fair, once the application was submitted it still took 6 years for approval. There are likely large procedural costs in doing the exemptions and testing that make inaction preferable. So, in some sense exemptions and lacking interest in approval may be problems of their own creation, but on net the overall outcome seems fairly reasonable. Actual improvements in procedural matters are likely too nuanced for a random layperson like myself to comment on.
  - civilitty 3y ago
    > The actual moral of the story maybe is that we should let third partys submit applications? The application isn't a single page form, it's hundreds to thousands of pages detailing everything about the clinical trials ranging from the success criteria for each phase, the doctors and hospitals involved in the trials, and even tiny details like how much blood is going to be drawn, when it will be drawn, and how it's going to be tested. They're impossible to write without the participation of almost everyone involved in the process since a significant part of premarketing approval is quality control of the final drug manufacturing process.
    - 3y ago
- treeman79 3y ago
  Went through this for an autoimmune condition with extreme nerve pain. Support forums are full of people that say LDN is a fantastic drug and works wonders. I was on opioids begging doctors to let me try LDN so I could get off the opids. All Refused since they weren’t familiar with LDN. I was finally able to get it online. I no longer take pain medication. Life is basically back to normal.
- msla 3y ago
  Right to try is a cruel scam: https://sciencebasedmedicine.org/the-cruel-sham-of-right-to-try-takes-a-giant-step-towards-becoming-federal-law/ https://sciencebasedmedicine.org/the-cruel-sham-of-right-to-... > So-called “right-to-try” is a cruel sham that holds out the false hope of survival to terminally ill patients and their families. In return, all they have to give up is patient protections and agree to pay to be guinea pigs to test a drug company’s product. The product of an ideology that uses the terminally ill as shields to hide the ideological motives behind the law, which are to hobble the FDA, right-to-try is a terrible idea.
  - AbrahamParangi 3y ago
    Wild to say this to someone with everything to gain and little to lose. What is the terrible fate you're protecting terminally ill patients from? Is it worse than death?
    - HWR_14 3y ago
      There are things worse than death. And then there are things that are bad when added to deaths. In the first category might be "scammers who absorb so much cash that they prevent real cures from being researched". In the second might be "people who squander their family's financial future on magic beans in futile attempt to live, but die anyway". No one would opt into volunteer to be in the second group. But, I can see a lot of, e.g. 50-year-olds, taking a risk thinking they can refill the college-education funds and retirement funds by just working longer than they intended. I would imagine when dying one of the comforting thoughts is that your estate will continue being able to care for loved ones after you are gone.
      - AbrahamParangi 3y ago
        I mean, end of life medical care is already incredibly expensive with very, very little benefit in terms of QALYs saved. We do it anyway. I fail to see how this is different, let people fight to live.
        3y ago
- HWR_14 3y ago
  Patients who are near the palliative-stage can try many drugs in the FDA approval process. The doctor has to get "permission", but that is granted over 99% of the time. IIRC, it mostly involves making sure the doctor has read up on the research, believes it is necessary to save the patient's life, and agrees to report back on the treatment to the FDA. If there really is a treatment that is significantly better than current treatments, have your doctors talked to you about this? It was codified into law about a decade ago, but that's not so new that they shouldn't be aware of the program.
- car 3y ago
  Sorry to read about your illness. Without knowing specifics, it is sometimes possible to get access to trial drugs via a compassionate use exemption[0]. You could find out which centers close to you are part of the trial, and contact them about getting access to treatment. I've previously contacted a drug manufacturers directly to inquire about access via a trial center. This was for a pancreatic cancer drug made by Halozyme. The trial was ultimately halted due to disappointing results. Please take into account that a drug still in trial may ultimately fail to meet its endpoints, as in the above case. [0]https://www.fda.gov/news-events/public-health-focus/expanded-access https://www.fda.gov/news-events/public-health-focus/expanded...
- sam2426679 3y ago
  What treatment is this? Atezolizumab? (I also have recurrent SCC of the tongue.)
  - jseliger 3y ago
    Moderna mRNA-4359: https://clinicaltrials.gov/ct2/show/NCT05533697 https://clinicaltrials.gov/ct2/show/NCT05533697. BioNTech has a similar treatment that's also been apparently slow to launch Phase III trials.
- taylodl 3y ago
  I understand where you're coming from, but as the parent of someone in the field of pharmaceutical research they have a different view. First, human beings aren't Guinea pigs. Yes, the FDA is slow - for damn good reasons. We didn't use to do things this way and then we changed it to fix problems. There are reasons things are the way they are and it's very well-understood in the medical field. Medicine is not a move fast and cause pain and suffering kind of field or move fast and kill people kind of field. They're very conservative. Two, since human beings aren't Guinea pigs when we do do experiments on them with drugs that have been through a very thorough and extensive pipeline already, they're looking for very specific things. This tends to make a very small population of patients eligible for a trial. Three, trials are expensive. These aren't drugs that have been scaled-out in production. The costs tend to be exceedingly exorbitant. The medical field is very well aware of the inelastic demand for their services and this opens up new avenues for the unscrupulous to prey on people. Like the used to do in the "good ol' days." Finally, the fact the treatment you would like to pursue is still "stuck" in clinical trials is indicative they're not convinced of the efficacy of the treatment. I can tell you lots of "promising" treatments never make it out of clinical trials. That's the nature of the beast. Most ideas are dead-ends. My advice? Don't chase unicorns. Sadly, I've watched too many people in my family die while chasing unicorns and getting obsessed with treatments that are in trial. There are always treatments in trial. Live your life and enjoy what time you have to the fullest.
  - WalterBright 3y ago
    The counter to this is Sam Pelzmann's "Regulation of Pharmaceutical Innovation" https://www.amazon.com/Regulation-Pharmaceutical-Innovation-Amendments-Evaluative/dp/0844731285/ https://www.amazon.com/Regulation-Pharmaceutical-Innovation-... where he shows, with statistics, that moving fast saves more lives than it costs.
    - taylodl 3y ago
      Given all the human pain and suffering economists have wrought may I suggest we insist they stay in their own wheelhouse? Also, it's easy to look back, with statistics, and say had we approved a successful drug/treatment earlier then we could have saved lives. That's survivor bias as it ignores all the treatments that were found to be ineffective or worse and what those effects would have been had they been administered to a wider group earlier.
- BrandoElFollito 3y ago
  I think that patients should be able to choose, but in reality the advantage will be for them only. Due to the lack of control groups them taking the pill does not make the science go forward (in the sense that it is an indication for the use). I believe however that they're is a great interest in the stopping effect: the evidence that the treatment is ultimately harmful. Still, this is a win-win: - if the patient gets better, good for them. Does not help the pharma company. - if the patient gets collateral negative effects, too bad for them (but they were very bad anyway). This helps the pharma company. Coupled with euthanasia, this would be a humanitarian solution for the extremely sick.
  - RealityVoid 3y ago
    I'm a bit puzzled why you couldn't extract useful information even _without_ a control group. Let's say we have a disease that we know that kills you. If you take the treatment and you don't die, we have pretty damn' positive evidence it works. The control group is the... You know... Many other people that don't take the medicine and die.
    - BrandoElFollito 3y ago
      This is probably a good indication, but you do not know if it is the pill that is making the effect. It may also be the placebo effect. It may also be that on day 6 you get better (no matter of you took the pill or not), and then worse on day 20, but much worse than without the pill. Still, this is a statistical wink so to speak (paraphrasing xkcd (https://xkcd.com/552/ https://xkcd.com/552/)). To be clear: I am all for patients experimenting on themselves when they do not have much to lose (and whenever they please, but they have to take their responsibilities then). Plus euthanasia if the experiment goes south.
- nitwit005 3y ago
  > They are risking essentially nothing. In some cases this is true, but people often want to risk their chance of survival with conventional treatments.
- megaman821 3y ago
  Since any unproven treatment has a chance to produce immense suffering, you would need to pair this with a right to end your life too. That isn't right that exists in too many places now.
- deleted 3y ago
  [deleted]
- P_I_Staker 3y ago
  IMO opinion this is an even bigger issue with other medications. Doctors shouldn't get to decide that you should live in pain, or be trapped in a prison of your mind. In our current society, a doctor has the unilateral decision whether to end a patients life (in so far as they are able to thrive in our society). Access to stimulant and opioid medication should be a right for patients with these conditions. We don't need a doctor to baby us, when they would certainly have access for themselves and their children. The majority of doctors would not give up their career, move in with their parents, or tell their kids that college is not for them.
908B64B197 3y ago
Isn't the answer simply: My body my choice?
- krick 3y ago
  It should be. It isn't. The usual situation.
  - asdfman123 3y ago
    One complexity is that patients might not be in a good place to evaluate whether a drug is truly viable or it's what they actually want, and they might face pressure from doctors or drug companies. But I generally agree that it should be the patient's choice.
    - zhivota 3y ago
      Right, also the state has a vested interest here, because patients bankrupting themselves on snake oil will result in more public money being spent on treatment.
    - Spivak 3y ago
      We already have a process for this called informed consent. * Medication must be prescribed by and supervised by an MD. * Doctor has to give you paperwork explaining everything about the drug, that it's not approved and experimental, what the known side effects are and personally go through it with you allowing you to ask questions. It's not currently required but you could also mandate a short cooling off period to avoid rash decisions. In an odd twist of fate the political faction that would love to eliminate the FDA also wants to eliminate informed consent because people are getting medical care they don't approve of. How dare the FDA tell you what you can and can't do with your body -- only we should be allowed to do that lololol
- bequanna 3y ago
  Right, but consider that this is a group of people that is vulnerable and desperate. They are ripe for being taken advantage of.
renewiltord 3y ago
We appointed gatekeepers and gave them a gate. Now they keep the gate, though our salvation is on the other side. It is the nature of gatekeepers to keep gates. So we perish, our gates well-kept.
- tdeck 3y ago
  The other side of the gate is Tijuana where you can spend your family's life savings to die in a clinic offering some quack treatment.
  - renewiltord 3y ago
    Haha, for others. Not for me. I do not constrain myself to the law even here in the US, so I'm okay.
hobotime 3y ago
My dad willingly tried an experimental drug. It killed him, but he would have died a week or two later. We now know that the drug doesn't work as well as we all would like. His death was valuable, and moved our scientific knowledge forward.
- VirusNewbie 3y ago
  Sorry to hear. I do agree, that was a noble death. Respect to your father for the choice he made.
angry_moose 3y ago
I'm in medical and one major issue with Compassionate Use programs [1] is there often just isn't the supply yet to divert doses/devices to non-trial patients. By definition they are pre-release treatments, which means manufacturing is still ramping up and is often only available in small quantities. We would love to be able to provide access to our device to everyone (its quite promising), but we are barely able to meet demand for the clinical trial. With those restrictions, the call was made that we had to end compassionate use treatments for the foreseeable future - with limited supply they had to be devoted solely to the clinical trial, which is designed to give the maximum possible data about efficacy, not just anyone it might help. 1) https://www.fda.gov/news-events/public-health-focus/expanded-access https://www.fda.gov/news-events/public-health-focus/expanded... - The FDA is actually pretty good about allowing these treatments
- hinkley 3y ago
  Sounds a lot like Mythical Man Month territory as well. More patients means more techs and more doctors to offer advice/test for side effects, and you can’t just wave a wand and get those. You have to invest in people to roll out a product.
  - civilitty 3y ago
    Exactly. Patient selection in clinical trials is already notoriously difficult even with phase I trials where it's a few dozen healthy people at most. Finding the right patients so your control and test groups don't have a lot of confounding factors is a field unto itself. Doing so with terminal patients, who often have a lot of things going on including just the psychology of dying, is even more so. Almost everyone hires out to contract research organizations that have entire departments dedicated to the process with years long relationships with major hospitals and patient groups that serve as "sales funnels" for their clinical trials.
- spoonfeeder006 3y ago
  Could they increase supply in anticipation of dying people wanting to use them? Might be harder to estimate than a normally released product though
lacker 3y ago
It seems like there's a lot of lower hanging fruit here. For example, we could let people in the US take any drug that has been approved in any of the EU, England, Canada, or Japan. A drug isn't really "unproven" if one of the world's top-tier medical establishments approves it. The core problem is that our current drug approval process is slow, expensive, and risk-averse. The medical establishment seems very inward-focused, ignoring what happens in other countries, even the countries that are just about as sophisticated as we are.
- tdeck 3y ago
  I'm not sure what the ultimate cost/benefit to this proposal would be, but it's worth noting that thalidomide was approved in many other countries but not the US.
- hinkley 3y ago
  I’ve forgotten what drug but I recall a lot of people being salty about five years back because there was a much more effective treatment in Europe for some chronic condition and the ETA for FDA approval was still multiple years. It’s not often such a large time lag that but sometimes the deck gets stacked against you.
- Spivak 3y ago
  I like this a lot and it would end my importing the good sunscreen from Europe because the FDA is reeeeeally slow.
  - H8crilA 3y ago
    Are you sure it's good sunscreen, and not just a lie about the SPF? There have been many of those around the world, stuff that's N sold as 1.5*N.
    - Spivak 3y ago
      What I get is La Roche-Posay Anthelios UVmune 400 Invisible Fluid. The American version doesn't protect as much against UVA because the new fancy filters haven't been approved by the FDA yet.
Simulacra 3y ago
Right to try should be absolutely fundamental. If patients want to try unproven drugs, give it to them, it's their body, their lives. Especially if they're terminal. I see absolutely no downside. The government really has no business telling us how to manage our healthcare, but dammit they try!
paxys 3y ago
Lipitor was formulated in 1985, went through an expensive and exhaustive trials process which concluded in 1994, and hit the market in 1996. Today it is one of the best selling drugs in the world, has revolutionized heart health, and saves tens of thousands of lives in the US annually. So was Lipitor’s development and approval process a failure? If you ask some patients and their families who were stuck in the early 90s with hope but no access to the drug, they would probably say so. And I understand the emotions involved, but the truth is that if human civilization has existed without a lifesaving treatment for hundreds of thousands of years, delaying it for a couple more to better under its effectiveness is the right decision for the public good.
- xxpor 3y ago
  >dthe truth is that if human civilization has existed without a lifesaving treatment for hundreds of thousands of years, delaying it for a couple more to better under its effectiveness is the right decision for the public good. I don't understand how that's the counterfactual though. Let's say the patents we're talking about are ones that in the early 90s had a 90%+ chance of dying without Lipitor. Not giving them the drug simply to have a control group is just as morally fraught as giving people completely untested drugs that kills them. To suggest otherwise is just status quo bias. It's clearly a complex issue where you draw the line, but we should be able to have an intelligent conversation as a society about probabilities and tradeoffs.
  - paxys 3y ago
    People who don’t get a drug while it is under development aren’t in a control group. People in a clinical trial who don’t get the drug are in the control group. Yes it is a morally tricky situation, but the people who signed up are aware of it. Everyone else simply doesn’t get the drug because the drug hasn’t been approved yet.
    - AbrahamParangi 3y ago
      The point that people are making is that it's the trolley problem. Yes you actively kill one person by making a drug available prematurely but you kill 5 people through inaction otherwise.
Glench 3y ago
I'd also love to see psychedelic-assisted therapy approved for therapeutic use in dying patients. The outcome studies for exactly this scenario have been really good from my understanding.
- P_I_Staker 3y ago
  I'm not throwing stones, but I think many people don't realize how hated these molecules are in the mental health community. If you were to tell your psych that you're taking psychedelics it could permanently limit your medical options, even outside of mental health... most therapists aren't much better.
  - Glench 3y ago
    Ooh I really welcome your perspective! That sucks. Most of the therapists and doctors I know are really interested in their therapeutic use —wary, but open if rigorous studies show benefits. Hopefully there will be less stigma as their supervised use begins penetrating our culture.
    - P_I_Staker 3y ago
      I'm not really saying that they're all against research, but I just find it interesting how few people seem to realize that the mental health community is insanely anti-drug. It's like a purity cult. Also, it seems to strangely follow cultural tendencies. So cigs are unhealthy but okay, you can drink a little, have your coffee and now some cannabis is okay, but no psychedelics, stimulants, etc... they really seem to be pulling bullshit out of their ass. I get the reason why drugs are viewed as such a problem, but I think it's crazy that people aren't considering mass discrimination and stigmatization by the medical community as a problem in mental health and drug addiction... it's wild. I haven't heard a single mention of this, and I follow this issue. So many people acting like doctors are part of the solution when they're one of the biggest parts of the problem. One of the most dangerous things you can do is talk your doctor if you have an issue with mental health or substance.
Am4TIfIsER0ppos 3y ago
If it will make them better there is no problem. If it won't make them better it might be a scam. If it will make them worse just call it euthanasia.
mynonameaccount 3y ago
What else do they have to lose? The problem with the US health care system is that everything is reliant on a medical professional. Want a blood test, a medical professional has generate it. Want a ultrasound, go to a medical professional first. I am in charge of my health. I don't need no stinking doctor who could give a shit what happens to me. They get paid no matter. I should be able to schedule and pay for a full body scan if I want.
- pookah 3y ago
  [dead]
- juve1996 3y ago
  No, the problem is cost. The medical professional part is secondary because no one wants to pay for hypochondriacs who think their cough at 25 is stage 4 lung cancer based on webMD research, because getting a full body scan is expensive. If it was cheap then it wouldn't matter.
  - edgan 3y ago
    You could argue that it will stay expensive, because the medical industry is acting as gatekeepers. The prime example of this is hearing aids.
Havoc 3y ago
Sure. If we've got to test dangerous drugs on humans (which at some point you must) - this is about as ethical as it gets I think.

103 points by jseliger 3y ago

In my view, patients should have a "right to try," which is part of fundamental freedom—and this is particularly true for palliative-stage patients without a route to a cure anyway. They are risking essentially nothing. The FDA is too slow and that's costing lives: https://marginalrevolution.com/marginalrevolution/2021/08/the-fda-is-still-much-too-strict.html https://marginalrevolution.com/marginalrevolution/2021/08/th.... The issue is personal for me, too, because I have a squamous cell carcinoma (SCC) recurrence in the tongue, and the treatment that is most likely to cure it is still stuck in clinical trials. In other words, there's a reasonable shot I perish because the FDA is slow, in which case I'll wind up in the "invisible graveyard" that Tabarrok discusses.

paulpauper 3y ago
and the treatment that is most likely to cure it is still stuck in clinical trials. it seems like you are contradicting yourself. if it's likely to cure, then that would be borne out by the trial? And then it would be rushed for approval. The vast, vast majority of clinal trials for cancer are unsuccessful. A 'successful' drug may add a few months of life vs placebo at a cost of $10k or more per month.
- Mattasher 3y ago
  > if it's likely to cure, then that would be borne out by the trial? And then it would be rushed for approval. I'm not sure you know how long these things take, even when they work well. Also, the failure to show a positive clinical effect in a trial mean one doesn't exist, especially at the individual level.
seanmcdirmid 3y ago
They had this debate in China recently and the problem was conflict of interest (lots of pricey snake oil for dying patients who can come up with the money). The market has to be regulated even for dying people, if only to prevent scams.
- warent 3y ago
  Did the Chinese government ultimately regulate the market to protect people and prevent this kind of corruption?
  - DiscourseFan 3y ago
    The regulation is approval by a governmental agency through clinical trials
  - dspillett 3y ago
    IIRC it did, though the cynic in me would suggest that by “this kind of corruption” what it prevents is the kind of corruption that government officials don't benefit from. I trust the Chinese government less than I trust my own with regard to doing the right thing (just because it is the right thing or indeed at all), and that is a pretty low bar…
  - seanmcdirmid 3y ago
    This wiki article is probably the best place to start: https://en.m.wikipedia.org/wiki/Death_of_Wei_Zexi https://en.m.wikipedia.org/wiki/Death_of_Wei_Zexi Then there was some movement on the issue in 2019: https://www.bloomberg.com/news/features/2019-12-10/cancer-treatment-china-mulls-looser-experimental-therapy-rules https://www.bloomberg.com/news/features/2019-12-10/cancer-tr... I’m not sure where they ended up due to COVID happening next.
- mitthrowaway2 3y ago
  Perhaps the patients should be allowed to use experimental treatments only under the condition that it is offered for free; the upside for the company is that if it works, they get the evidence of efficacy.
  - rafark 3y ago
    This should be the solution. If they’re trials for an unproven solution, why should they pay anything at all. I’m any case, it should be the other way around; it’s the companies who should pay the person for subjecting them to something very likely to be dangerous and painful. In any case, I agree with the sentiment here. People should have the right to choose.
deleted 3y ago
[deleted]
jahnu 3y ago
On this topic here is an excellent examination of it https://timharford.com/2020/06/cautionary-tales-the-spreadsheet-of-life-and-death/ https://timharford.com/2020/06/cautionary-tales-the-spreadsh...
Veserv 3y ago
The link you posted has a addendum which links to this: https://astralcodexten.substack.com/p/details-of-the-infant-fish-oil-story https://astralcodexten.substack.com/p/details-of-the-infant-... In the more well researched followup by the same person, the author of Astral Codex, we see that the FDA did not block or slow the approval. It was that the manufacturer had no interest in even submitting a application. In fact, the FDA regularly granted usage exemptions, granted a broad exemption for research, and even directly funded one of the first trials even though they are not primarily a funding body. The actual moral of the story maybe is that we should let third partys submit applications? It seems like there would be little risk of bad outcomes as they still need to do the approval process. It aligns incentives better as the people ultimately at risk can deploy resources comparable to their QoL improvement instead of the expected increased sales volume at current prices. There is a obvious problem that the production process is inextricably linked to the final output so a non-manufacturer has limited control and insight into a core component that introduces the possibility of regression, but it seems relatively doable to develop protocols for handling that if they do not already exist. edit: To be fair, once the application was submitted it still took 6 years for approval. There are likely large procedural costs in doing the exemptions and testing that make inaction preferable. So, in some sense exemptions and lacking interest in approval may be problems of their own creation, but on net the overall outcome seems fairly reasonable. Actual improvements in procedural matters are likely too nuanced for a random layperson like myself to comment on.
- civilitty 3y ago
  > The actual moral of the story maybe is that we should let third partys submit applications? The application isn't a single page form, it's hundreds to thousands of pages detailing everything about the clinical trials ranging from the success criteria for each phase, the doctors and hospitals involved in the trials, and even tiny details like how much blood is going to be drawn, when it will be drawn, and how it's going to be tested. They're impossible to write without the participation of almost everyone involved in the process since a significant part of premarketing approval is quality control of the final drug manufacturing process.
  - 3y ago
treeman79 3y ago
Went through this for an autoimmune condition with extreme nerve pain. Support forums are full of people that say LDN is a fantastic drug and works wonders. I was on opioids begging doctors to let me try LDN so I could get off the opids. All Refused since they weren’t familiar with LDN. I was finally able to get it online. I no longer take pain medication. Life is basically back to normal.
msla 3y ago
Right to try is a cruel scam: https://sciencebasedmedicine.org/the-cruel-sham-of-right-to-try-takes-a-giant-step-towards-becoming-federal-law/ https://sciencebasedmedicine.org/the-cruel-sham-of-right-to-... > So-called “right-to-try” is a cruel sham that holds out the false hope of survival to terminally ill patients and their families. In return, all they have to give up is patient protections and agree to pay to be guinea pigs to test a drug company’s product. The product of an ideology that uses the terminally ill as shields to hide the ideological motives behind the law, which are to hobble the FDA, right-to-try is a terrible idea.
- AbrahamParangi 3y ago
  Wild to say this to someone with everything to gain and little to lose. What is the terrible fate you're protecting terminally ill patients from? Is it worse than death?
  - HWR_14 3y ago
    There are things worse than death. And then there are things that are bad when added to deaths. In the first category might be "scammers who absorb so much cash that they prevent real cures from being researched". In the second might be "people who squander their family's financial future on magic beans in futile attempt to live, but die anyway". No one would opt into volunteer to be in the second group. But, I can see a lot of, e.g. 50-year-olds, taking a risk thinking they can refill the college-education funds and retirement funds by just working longer than they intended. I would imagine when dying one of the comforting thoughts is that your estate will continue being able to care for loved ones after you are gone.
    - AbrahamParangi 3y ago
      I mean, end of life medical care is already incredibly expensive with very, very little benefit in terms of QALYs saved. We do it anyway. I fail to see how this is different, let people fight to live.
      - 3y ago
HWR_14 3y ago
Patients who are near the palliative-stage can try many drugs in the FDA approval process. The doctor has to get "permission", but that is granted over 99% of the time. IIRC, it mostly involves making sure the doctor has read up on the research, believes it is necessary to save the patient's life, and agrees to report back on the treatment to the FDA. If there really is a treatment that is significantly better than current treatments, have your doctors talked to you about this? It was codified into law about a decade ago, but that's not so new that they shouldn't be aware of the program.
car 3y ago
Sorry to read about your illness. Without knowing specifics, it is sometimes possible to get access to trial drugs via a compassionate use exemption[0]. You could find out which centers close to you are part of the trial, and contact them about getting access to treatment. I've previously contacted a drug manufacturers directly to inquire about access via a trial center. This was for a pancreatic cancer drug made by Halozyme. The trial was ultimately halted due to disappointing results. Please take into account that a drug still in trial may ultimately fail to meet its endpoints, as in the above case. [0]https://www.fda.gov/news-events/public-health-focus/expanded-access https://www.fda.gov/news-events/public-health-focus/expanded...
sam2426679 3y ago
What treatment is this? Atezolizumab? (I also have recurrent SCC of the tongue.)
- jseliger 3y ago
  Moderna mRNA-4359: https://clinicaltrials.gov/ct2/show/NCT05533697 https://clinicaltrials.gov/ct2/show/NCT05533697. BioNTech has a similar treatment that's also been apparently slow to launch Phase III trials.
taylodl 3y ago
I understand where you're coming from, but as the parent of someone in the field of pharmaceutical research they have a different view. First, human beings aren't Guinea pigs. Yes, the FDA is slow - for damn good reasons. We didn't use to do things this way and then we changed it to fix problems. There are reasons things are the way they are and it's very well-understood in the medical field. Medicine is not a move fast and cause pain and suffering kind of field or move fast and kill people kind of field. They're very conservative. Two, since human beings aren't Guinea pigs when we do do experiments on them with drugs that have been through a very thorough and extensive pipeline already, they're looking for very specific things. This tends to make a very small population of patients eligible for a trial. Three, trials are expensive. These aren't drugs that have been scaled-out in production. The costs tend to be exceedingly exorbitant. The medical field is very well aware of the inelastic demand for their services and this opens up new avenues for the unscrupulous to prey on people. Like the used to do in the "good ol' days." Finally, the fact the treatment you would like to pursue is still "stuck" in clinical trials is indicative they're not convinced of the efficacy of the treatment. I can tell you lots of "promising" treatments never make it out of clinical trials. That's the nature of the beast. Most ideas are dead-ends. My advice? Don't chase unicorns. Sadly, I've watched too many people in my family die while chasing unicorns and getting obsessed with treatments that are in trial. There are always treatments in trial. Live your life and enjoy what time you have to the fullest.
- WalterBright 3y ago
  The counter to this is Sam Pelzmann's "Regulation of Pharmaceutical Innovation" https://www.amazon.com/Regulation-Pharmaceutical-Innovation-Amendments-Evaluative/dp/0844731285/ https://www.amazon.com/Regulation-Pharmaceutical-Innovation-... where he shows, with statistics, that moving fast saves more lives than it costs.
  - taylodl 3y ago
    Given all the human pain and suffering economists have wrought may I suggest we insist they stay in their own wheelhouse? Also, it's easy to look back, with statistics, and say had we approved a successful drug/treatment earlier then we could have saved lives. That's survivor bias as it ignores all the treatments that were found to be ineffective or worse and what those effects would have been had they been administered to a wider group earlier.
BrandoElFollito 3y ago
I think that patients should be able to choose, but in reality the advantage will be for them only. Due to the lack of control groups them taking the pill does not make the science go forward (in the sense that it is an indication for the use). I believe however that they're is a great interest in the stopping effect: the evidence that the treatment is ultimately harmful. Still, this is a win-win: - if the patient gets better, good for them. Does not help the pharma company. - if the patient gets collateral negative effects, too bad for them (but they were very bad anyway). This helps the pharma company. Coupled with euthanasia, this would be a humanitarian solution for the extremely sick.
- RealityVoid 3y ago
  I'm a bit puzzled why you couldn't extract useful information even _without_ a control group. Let's say we have a disease that we know that kills you. If you take the treatment and you don't die, we have pretty damn' positive evidence it works. The control group is the... You know... Many other people that don't take the medicine and die.
  - BrandoElFollito 3y ago
    This is probably a good indication, but you do not know if it is the pill that is making the effect. It may also be the placebo effect. It may also be that on day 6 you get better (no matter of you took the pill or not), and then worse on day 20, but much worse than without the pill. Still, this is a statistical wink so to speak (paraphrasing xkcd (https://xkcd.com/552/ https://xkcd.com/552/)). To be clear: I am all for patients experimenting on themselves when they do not have much to lose (and whenever they please, but they have to take their responsibilities then). Plus euthanasia if the experiment goes south.
nitwit005 3y ago
> They are risking essentially nothing. In some cases this is true, but people often want to risk their chance of survival with conventional treatments.
megaman821 3y ago
Since any unproven treatment has a chance to produce immense suffering, you would need to pair this with a right to end your life too. That isn't right that exists in too many places now.
deleted 3y ago
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P_I_Staker 3y ago
IMO opinion this is an even bigger issue with other medications. Doctors shouldn't get to decide that you should live in pain, or be trapped in a prison of your mind. In our current society, a doctor has the unilateral decision whether to end a patients life (in so far as they are able to thrive in our society). Access to stimulant and opioid medication should be a right for patients with these conditions. We don't need a doctor to baby us, when they would certainly have access for themselves and their children. The majority of doctors would not give up their career, move in with their parents, or tell their kids that college is not for them.

908B64B197 3y ago

Isn't the answer simply: My body my choice?

krick 3y ago
It should be. It isn't. The usual situation.
- asdfman123 3y ago
  One complexity is that patients might not be in a good place to evaluate whether a drug is truly viable or it's what they actually want, and they might face pressure from doctors or drug companies. But I generally agree that it should be the patient's choice.
  - zhivota 3y ago
    Right, also the state has a vested interest here, because patients bankrupting themselves on snake oil will result in more public money being spent on treatment.
  - Spivak 3y ago
    We already have a process for this called informed consent. * Medication must be prescribed by and supervised by an MD. * Doctor has to give you paperwork explaining everything about the drug, that it's not approved and experimental, what the known side effects are and personally go through it with you allowing you to ask questions. It's not currently required but you could also mandate a short cooling off period to avoid rash decisions. In an odd twist of fate the political faction that would love to eliminate the FDA also wants to eliminate informed consent because people are getting medical care they don't approve of. How dare the FDA tell you what you can and can't do with your body -- only we should be allowed to do that lololol
bequanna 3y ago
Right, but consider that this is a group of people that is vulnerable and desperate. They are ripe for being taken advantage of.

renewiltord 3y ago

We appointed gatekeepers and gave them a gate. Now they keep the gate, though our salvation is on the other side. It is the nature of gatekeepers to keep gates. So we perish, our gates well-kept.

tdeck 3y ago
The other side of the gate is Tijuana where you can spend your family's life savings to die in a clinic offering some quack treatment.
- renewiltord 3y ago
  Haha, for others. Not for me. I do not constrain myself to the law even here in the US, so I'm okay.

hobotime 3y ago

My dad willingly tried an experimental drug. It killed him, but he would have died a week or two later. We now know that the drug doesn't work as well as we all would like. His death was valuable, and moved our scientific knowledge forward.

VirusNewbie 3y ago
Sorry to hear. I do agree, that was a noble death. Respect to your father for the choice he made.

angry_moose 3y ago

I'm in medical and one major issue with Compassionate Use programs [1] is there often just isn't the supply yet to divert doses/devices to non-trial patients. By definition they are pre-release treatments, which means manufacturing is still ramping up and is often only available in small quantities. We would love to be able to provide access to our device to everyone (its quite promising), but we are barely able to meet demand for the clinical trial. With those restrictions, the call was made that we had to end compassionate use treatments for the foreseeable future - with limited supply they had to be devoted solely to the clinical trial, which is designed to give the maximum possible data about efficacy, not just anyone it might help. 1) https://www.fda.gov/news-events/public-health-focus/expanded-access https://www.fda.gov/news-events/public-health-focus/expanded... - The FDA is actually pretty good about allowing these treatments

hinkley 3y ago
Sounds a lot like Mythical Man Month territory as well. More patients means more techs and more doctors to offer advice/test for side effects, and you can’t just wave a wand and get those. You have to invest in people to roll out a product.
- civilitty 3y ago
  Exactly. Patient selection in clinical trials is already notoriously difficult even with phase I trials where it's a few dozen healthy people at most. Finding the right patients so your control and test groups don't have a lot of confounding factors is a field unto itself. Doing so with terminal patients, who often have a lot of things going on including just the psychology of dying, is even more so. Almost everyone hires out to contract research organizations that have entire departments dedicated to the process with years long relationships with major hospitals and patient groups that serve as "sales funnels" for their clinical trials.
spoonfeeder006 3y ago
Could they increase supply in anticipation of dying people wanting to use them? Might be harder to estimate than a normally released product though

lacker 3y ago

It seems like there's a lot of lower hanging fruit here. For example, we could let people in the US take any drug that has been approved in any of the EU, England, Canada, or Japan. A drug isn't really "unproven" if one of the world's top-tier medical establishments approves it. The core problem is that our current drug approval process is slow, expensive, and risk-averse. The medical establishment seems very inward-focused, ignoring what happens in other countries, even the countries that are just about as sophisticated as we are.

tdeck 3y ago
I'm not sure what the ultimate cost/benefit to this proposal would be, but it's worth noting that thalidomide was approved in many other countries but not the US.
hinkley 3y ago
I’ve forgotten what drug but I recall a lot of people being salty about five years back because there was a much more effective treatment in Europe for some chronic condition and the ETA for FDA approval was still multiple years. It’s not often such a large time lag that but sometimes the deck gets stacked against you.
Spivak 3y ago
I like this a lot and it would end my importing the good sunscreen from Europe because the FDA is reeeeeally slow.
- H8crilA 3y ago
  Are you sure it's good sunscreen, and not just a lie about the SPF? There have been many of those around the world, stuff that's N sold as 1.5*N.
  - Spivak 3y ago
    What I get is La Roche-Posay Anthelios UVmune 400 Invisible Fluid. The American version doesn't protect as much against UVA because the new fancy filters haven't been approved by the FDA yet.

Simulacra 3y ago

Right to try should be absolutely fundamental. If patients want to try unproven drugs, give it to them, it's their body, their lives. Especially if they're terminal. I see absolutely no downside. The government really has no business telling us how to manage our healthcare, but dammit they try!

paxys 3y ago

Lipitor was formulated in 1985, went through an expensive and exhaustive trials process which concluded in 1994, and hit the market in 1996. Today it is one of the best selling drugs in the world, has revolutionized heart health, and saves tens of thousands of lives in the US annually. So was Lipitor’s development and approval process a failure? If you ask some patients and their families who were stuck in the early 90s with hope but no access to the drug, they would probably say so. And I understand the emotions involved, but the truth is that if human civilization has existed without a lifesaving treatment for hundreds of thousands of years, delaying it for a couple more to better under its effectiveness is the right decision for the public good.

xxpor 3y ago
>dthe truth is that if human civilization has existed without a lifesaving treatment for hundreds of thousands of years, delaying it for a couple more to better under its effectiveness is the right decision for the public good. I don't understand how that's the counterfactual though. Let's say the patents we're talking about are ones that in the early 90s had a 90%+ chance of dying without Lipitor. Not giving them the drug simply to have a control group is just as morally fraught as giving people completely untested drugs that kills them. To suggest otherwise is just status quo bias. It's clearly a complex issue where you draw the line, but we should be able to have an intelligent conversation as a society about probabilities and tradeoffs.
- paxys 3y ago
  People who don’t get a drug while it is under development aren’t in a control group. People in a clinical trial who don’t get the drug are in the control group. Yes it is a morally tricky situation, but the people who signed up are aware of it. Everyone else simply doesn’t get the drug because the drug hasn’t been approved yet.
  - AbrahamParangi 3y ago
    The point that people are making is that it's the trolley problem. Yes you actively kill one person by making a drug available prematurely but you kill 5 people through inaction otherwise.

Glench 3y ago

I'd also love to see psychedelic-assisted therapy approved for therapeutic use in dying patients. The outcome studies for exactly this scenario have been really good from my understanding.

P_I_Staker 3y ago
I'm not throwing stones, but I think many people don't realize how hated these molecules are in the mental health community. If you were to tell your psych that you're taking psychedelics it could permanently limit your medical options, even outside of mental health... most therapists aren't much better.
- Glench 3y ago
  Ooh I really welcome your perspective! That sucks. Most of the therapists and doctors I know are really interested in their therapeutic use —wary, but open if rigorous studies show benefits. Hopefully there will be less stigma as their supervised use begins penetrating our culture.
  - P_I_Staker 3y ago
    I'm not really saying that they're all against research, but I just find it interesting how few people seem to realize that the mental health community is insanely anti-drug. It's like a purity cult. Also, it seems to strangely follow cultural tendencies. So cigs are unhealthy but okay, you can drink a little, have your coffee and now some cannabis is okay, but no psychedelics, stimulants, etc... they really seem to be pulling bullshit out of their ass. I get the reason why drugs are viewed as such a problem, but I think it's crazy that people aren't considering mass discrimination and stigmatization by the medical community as a problem in mental health and drug addiction... it's wild. I haven't heard a single mention of this, and I follow this issue. So many people acting like doctors are part of the solution when they're one of the biggest parts of the problem. One of the most dangerous things you can do is talk your doctor if you have an issue with mental health or substance.

Am4TIfIsER0ppos 3y ago

If it will make them better there is no problem. If it won't make them better it might be a scam. If it will make them worse just call it euthanasia.

mynonameaccount 3y ago

What else do they have to lose? The problem with the US health care system is that everything is reliant on a medical professional. Want a blood test, a medical professional has generate it. Want a ultrasound, go to a medical professional first. I am in charge of my health. I don't need no stinking doctor who could give a shit what happens to me. They get paid no matter. I should be able to schedule and pay for a full body scan if I want.

pookah 3y ago
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juve1996 3y ago
No, the problem is cost. The medical professional part is secondary because no one wants to pay for hypochondriacs who think their cough at 25 is stage 4 lung cancer based on webMD research, because getting a full body scan is expensive. If it was cheap then it wouldn't matter.
- edgan 3y ago
  You could argue that it will stay expensive, because the medical industry is acting as gatekeepers. The prime example of this is hearing aids.

Havoc 3y ago

Sure. If we've got to test dangerous drugs on humans (which at some point you must) - this is about as ethical as it gets I think.