4 ms·

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 ro

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.

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.