[HN Gopher] I am dying of squamous cell carcinoma, and potential...
___________________________________________________________________
I am dying of squamous cell carcinoma, and potential treatments are
out of reach
Author : theoldlove
Score : 713 points
Date : 2023-07-22 16:11 UTC (6 hours ago)
(HTM) web link (jakeseliger.com)
(TXT) w3m dump (jakeseliger.com)
| rediguanayum wrote:
| (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".
| can16358p wrote:
| There should be a universal law in human rights stating anyone
| can take anything into their own bodies and governments can
| never, ever prevent them.
|
| Governments/regulators deciding what you can put into your body
| is beyond ridiculous: applies to all substances and drugs.
|
| Inform about the potential risks and effects: sure.
|
| Prevent: never.
| hotpotamus wrote:
| 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.
| can16358p wrote:
| Yeah.
|
| It should be legal too. I'm not defending the use of it in
| any way, this is not about drugs but a more fundamental
| problem: governments deciding what you can and cannot put
| into your own body.
|
| They should inform people about potential dangers and effects
| of substances, and try to prevent the underlying reasons for
| people to, say, do heroin or fentanyl.
|
| But if someone wants to do it anyway, making it illegal just
| makes things worse as people will be stigmatized socially
| where they should be welcome/accepted the most, and they'll
| obtain the substance illegally and dangerously (who-knows-
| what-it's-laced-with and exact actual dosage) anyway.
|
| So just inform and support the people but make it legal and
| relatively safer to consume for harm reduction.
|
| But if someone wants to OD and kill themselves, I mean, it's
| sad but it's their own body and their own life.
| SanderNL wrote:
| 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.
| serial_dev wrote:
| If buying, selling, and possessing are all illegal, it's
| illegal for all practical purposes.
| hotpotamus wrote:
| I suppose that's the goal, but it's one of the interesting
| aspects of US law to me that taking drugs/being high on
| them is not a crime.
| RangerScience wrote:
| 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.)
| knodi123 wrote:
| 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!
| bhhaskin wrote:
| If the person is mentally able to make that decision for them
| selfs, then why not?
| PostOnce wrote:
| Additionaly, medicine companies aren't going to waste money
| trying stuff they know is likely to fail (like the example
| "radium asbestos")
| Veserv wrote:
| 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".
| meristem wrote:
| Mentally able =/= intellectually sophisticated to parse the
| legalese in the offer
| Terr_ wrote:
| > 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?
| kromem wrote:
| 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.
| Dylan16807 wrote:
| > Not OP, but laws against distribution? Absolutely.
|
| > Laws against consumption? A terrible idea.
|
| When we're on the topic of experimental medicine, it's the
| laws around distribution that have 99% of the effect.
| serial_dev wrote:
| 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.
| can16358p wrote:
| 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.
| kromem wrote:
| 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.
| m3kw9 wrote:
| [flagged]
| dmd wrote:
| [flagged]
| 01100011 wrote:
| 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.
| darkclouds wrote:
| The US govt makes medical information available online
| perhaps to give a more informed decision.
|
| "IL-6 Activities in the Tumour Microenvironment. Part 1"
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765074/#:~:tex.
| ...
|
| "Serum Level of Interleukin-6 in Patients with Oral Tongue
| Squamous cell Carcinoma"
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461844/
|
| "Interleukin-6 role in head and neck squamous cell carcinoma
| progression"
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698512/
|
| I also know from Google Scholar, that copper increases IL-6,
| penicillin breaks down into penicillamine, used to treat
| Wilson Disease, a copper metabolism difference, and I also
| know that Omega 3's look promising for reducing IL6.
|
| https://pubmed.ncbi.nlm.nih.gov/29803716/
|
| And thats just an example of a cursory look into SCC.
|
| Socialised medical costs, isnt always a panacea, knowledge
| and honesty is the closest you will get to a panacea for
| medicine.
| lamontcg wrote:
| Bigger problem is lawsuits by relatives.
|
| And if you protect the drug companies and doctors against
| those lawsuits, then you open the door to them exploiting
| desperate people.
| preinheimer wrote:
| 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".
| jddj wrote:
| 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.
| tqi wrote:
| > 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.
| balderdash wrote:
| 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?
| fnord77 wrote:
| separate efficacy testing from safety testing
| swayvil wrote:
| There is a religion. In it, good people are wealthy. Bad people,
| less so.
|
| It's a popular religion among the well-to-do. As you might
| imagine.
| xk_id wrote:
| The reality of cancer is a bit paralysing to anyone who has had
| direct exposure to it and there is nothing really overstated
| about it in the common sense of culture. Everyone's fight is
| different, because there are so many paths to take and they keep
| changing as research advances, but the time available is limited.
| Besides being restricted, cancer drugs are also notoriously
| expensive, but for the more self-determined individual there is
| the option of off-shore pharmacies (many based out of India) and
| perhaps even Chinese chemical labs (anything on AliBaba must be
| assumed to be completely unreliable; however, some of the labs
| which are referenced by scientific papers as suppliers are
| actually happy to do business after only a little bit of social
| engineering). Unfortunately this approach is limited to
| relatively simple pharmacological interventions; anything that
| requires complex medical procedures (including palliative care)
| and has to happen in a hospital will require normal legal
| compliance and the cooperation of a doctor. There are stories of
| people who have gone far and beyond to enrol into cutting edge
| clinical trials [1] - usually with the energetic support of a
| loved one. In those cases, even with the consent of a doctor, the
| logistics and expenses aren't trivial. There is much to say in
| general about the questionable role of institutions who gate-keep
| access to medical procedures under the pretext of protecting
| reckless consumers - but it wouldn't feel right to steer the
| conversation too much away from cancer.
|
| > This makes it nearly impossible for patients to find an
| appropriate clinical trial, discouraging all but the most
| stubborn-people like Mike Hindt, and people like Stephanie
| Florence. By her own admission, Florence, 44, a photographer
| living in Lewiston, Idaho, had to "bulldoze" her way into a trial
| by being persistent to the point of obnoxiousness.
|
| > When she found out she was a candidate for a new trial, she
| also learned another hard truth: trials don't come to patients.
| Patients have to go to the trials.
|
| > In August, she and her husband drove from Raleigh to Boston,
| despite having no place to stay. After a week in a hotel room
| paid for by their daughter, they wrote about their circumstances
| on a community blog. Several people in the area offered the
| couple rent-free housing during Price's treatment. In order to
| pay for food and other expenses, the couple are trying to sell
| their home, and Price's husband, laid off from his job at IBM,
| took a couple of part-time shifts a week at the outdoor-apparel
| store REI.
|
| [1] https://time.com/4270345/immunotherapy-pembro-clinical-
| trial...
| formulathree wrote:
| [dead]
| chris_va wrote:
| Anyone more knowledgeable know why they can't file for a single
| patient IND, assuming the vaccine is even acquirable?
| gumby wrote:
| This quote sounds like self interest in the article, but there is
| more to it:
|
| > If anything goes wrong," he argued, "think how bad it will look
| that we approved the drug so quickly"
|
| People who take an approved drug are relying on the result and
| authority of a scientific process -- across all drugs. Some scary
| results and people may start to fear the process, which may end
| up killing more people.
|
| That said I'm sympathetic to his plight and think that he sounds
| like a candidate for the compassionate use program. Any result
| would not help approval as who in such a program would volunteer
| to be randomized into a placebo arm? They'd just plead in a prior
| human administration disclosure section of any NDA.
|
| (Also, pragmatically, immunotherapy grate nets are customized and
| extremely expensive. Who will underwrite it? Not the drug company
| who would have nothing to gain, not the insurance company, and I
| doubt the patient could afford it).
|
| It's a sad story all around.
| notme1234 wrote:
| 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
| tux3 wrote:
| 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.
| msteffen wrote:
| 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.
| grammers wrote:
| > 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.
| atmosx wrote:
| > 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."
| haldujai wrote:
| > 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.
| tux3 wrote:
| >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.
| haldujai wrote:
| > 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.
| tux3 wrote:
| >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.
| haldujai wrote:
| > 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".
| riffraff wrote:
| I remember at least three instances in my country where the
| authorities were forced to allow people to use experimental
| treatments due to media clamor.
|
| In all three instances, the result was that the treatments were
| snake oil and people died that might have lived otherwise.
|
| It's easy to say "people who have no other options should get
| access to experimental treatments" but the problem is that
| people who have other options want those too, because nobody
| wants to go through chemotherapy or whatever.
|
| Medical authorities have a shitty job.
| justinclift wrote:
| > In all three instances, the result was that the treatments
| were snake oil and people died that might have lived
| otherwise.
|
| It seems like you're claiming that people who were given
| medical treatment after media attention _weren 't_ down to
| their last option(s)?
|
| If they were down to their last options, then they made their
| choice and it didn't work out.
| dannyobrien wrote:
| Maybe the fact that these are the ones you remember is an
| indication of the problem, rather than evidence that it is
| wrong.
| valine wrote:
| 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.
| jfk13 wrote:
| And how do we assess whether "someone understands the
| risk"? Often, I suspect _nobody_ really "understands" the
| risk of some minimally-tested, experimental treatment.
| MostlyStable wrote:
| This is a fully generalized argument against personal
| autonomy.
| jfk13 wrote:
| 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.
| Waterluvian wrote:
| I guess the FDA has a role in minimizing the market for snake
| oil.
| netsharc wrote:
| 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?
| exmadscientist wrote:
| 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.
| [deleted]
| thechao wrote:
| 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.
| joak wrote:
| 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)
| citruscomputing wrote:
| It should also be free after it's approved by the FDA.
| chroma wrote:
| How would that work? Would the government use money from
| taxes to pay the drug companies for their costs, plus
| some profit margin?
| joak wrote:
| 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)
| themitigating wrote:
| _This is a crime, but it 's very very hard to prove_
|
| Then how do you know it's prevalent?
| exmadscientist wrote:
| > Then how do you know it's prevalent?
|
| 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....
| civilitty wrote:
| _> 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._
|
| Like Steve Jobs.
|
| Fruit juice kills people.
| inconceivable wrote:
| clarification: fruit juice is basically pure fructose
| which cancer loves and your organs can't handle.
|
| actual fruit has fiber and you're unlikely to eat enough
| to cause harm.
| civilitty wrote:
| _woosh_
|
| 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.
| jonhohle wrote:
| 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.
| lacrimacida wrote:
| 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.
| realitygrill wrote:
| Would you email me? I'm really interested in learning about
| this. I have similar intuitions about places to avoid.
| londons_explore wrote:
| 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.
| krisoft wrote:
| > 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.
| Veserv wrote:
| 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.
| bialpio wrote:
| 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).
| krisoft wrote:
| > 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.
| K0balt wrote:
| 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.
| Google234 wrote:
| I don't think these people would be useful. Pharma needs
| controlled double blind studies to actually tell if the
| therapies work.
| CogitoCogito wrote:
| > 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.
| krisoft wrote:
| > 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?
| tremon wrote:
| 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?
| seqizz wrote:
| > 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.
| takinola wrote:
| 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.
| throwaway894345 wrote:
| 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.
| takinola wrote:
| 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.
| 7e wrote:
| 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.
| echelon wrote:
| 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.
| londons_explore wrote:
| 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.
| darkclouds wrote:
| >A simple way to stem most snake oil is to put all
| payments for snake oil treatments into escrow till the
| treatment is approved.
|
| It should be a escrow release when a patient is cured.
| Let the science and knowledge speak for itself instead of
| statistic doing the talking.
|
| The problem is these drugs companies are the stealth
| chemical weapons development program for the military.
| Broken_Hippo wrote:
| _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.
| darkclouds wrote:
| 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?
| CogitoCogito wrote:
| > 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.
| eggy wrote:
| 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.
| moralestapia wrote:
| >but the problem is that people who have other options want
| those too
|
| So, why can't one go through its own choice of treatment?
| Disregarding if its a good choice or a bad one.
| mcherm wrote:
| 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.
| dionidium wrote:
| > _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.
| lucianbr wrote:
| 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.
| MostlyStable wrote:
| 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.
| Given_47 wrote:
| 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
| lucianbr wrote:
| 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.
| Klinky wrote:
| 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.
| emodendroket wrote:
| Yes, and the FDA often does get pressured into approving
| treatments of dubious efficacy:
| https://arstechnica.com/science/2021/06/a-disgraceful-
| decisi...
|
| It's easy to understand the logic of desperate patients who
| will try anything but it doesn't seem right to allow
| manufacturers to profit hand over fist selling treatments
| that may not even do anything, or worse, outright cause harm.
| nine_k wrote:
| 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.
| yladiz wrote:
| C'mon, it's extremely disingenuous to compare abortion and
| contraception with untested treatment.
| toomuchtodo wrote:
| Assisted suicide and euthanasia are better examples. If
| you have autonomy to die, you should have autonomy to die
| trying not to.
| jfk13 wrote:
| Well, those are pretty controversial topics, so I'm not
| sure how much the analogy helps.
| nine_k wrote:
| It helps underline the hypocrisy of the current moral
| norms.
| peyton wrote:
| 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.
| nine_k wrote:
| I agree: not completely untested, but not tested
| sufficiently to get an FDA approval. They show early
| promising results.
|
| BTW people picking such experimental treatments would
| provide important data points.
| ejstronge wrote:
| > The FDA could work with sponsors to come up with a
| range of risk profiles and expand access.
|
| They indeed do this and have various avenues for
| treatments to be approved on expedited timelines.
| newaccount74 wrote:
| My friends mom bought a fancy light for 2000EUR 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.
| mustacheemperor wrote:
| 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.
| newZWhoDis wrote:
| If I'm terminal and my doctor and I want to try the
| treatment, who are the feds to tell me no?
|
| Screw 'em
| joshuamorton wrote:
| We are all, in some sense, terminal. At what number of
| months or years left to live does your terminality become
| sufficient to let you try whatever?
| hotpotamus wrote:
| 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.
| nextos wrote:
| 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.
| adamredwoods wrote:
| Keytruda, and other PD-1 blockers, have good science behind
| it. Many oncologists believe this is the true path to
| defeating many cancers.
|
| While PD-1 blockers may cause the immune system to attack
| another part of a patient's body, we have quite a few ways
| to treat those autoimmune issues.
| [deleted]
| dakial1 wrote:
| 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.
| Retric wrote:
| 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.
| eilertokyo wrote:
| Your comment makes something that happens quite rarely
| (1-5% based on agent, and not quickly) seem like it
| happens quite frequently.
| Retric wrote:
| Some of these trials had double digit percentage deaths
| within 30 days.
| adamredwoods wrote:
| Because the trials sometimes take on people with very
| little time left.
| Retric wrote:
| That's the estimate for number of people killed by the
| treatment not the number of people who died in total.
|
| You should be careful not to exclude trials cancelled
| early when considering how risky trials are.
| aantix wrote:
| 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.
| vore wrote:
| 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?
| sleight42 wrote:
| 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.
| melling wrote:
| This has been a common complaint for decades. We always want to
| try rush experimental drugs/procedures that "show promise".
|
| How often do these drugs, etc turn out to effective? 25 years
| ago we wanted to rush gene therapy and that didn't turn out
| well. Someone died. It probably set back gene therapy:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/
|
| I think the solution is to invest more into medical research
| now, then when we, or someone we know, eventually ends up with
| some horrible disease, (cancer(s), Alzheimer's, Parkinson's,
| etc) we'll know that we at least we made significant effort,
| and gave everyone a better chance, rather than settle for a
| "Hail Mary" drug near the end.
| appplication wrote:
| > 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.
| matteoraso wrote:
| >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.
| jasode wrote:
| _> 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.
| mlyle wrote:
| 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.
| jasode wrote:
| _> 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.
| haldujai wrote:
| 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.
| mlyle wrote:
| > 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.
| haldujai wrote:
| > 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.
| mlyle wrote:
| He may not be too far along from the standpoint of
| inclusion criteria; rather he believes he is likely to
| die before he is able to join the study.
| haldujai wrote:
| 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.
| fallingknife wrote:
| 3 years ago we wanted to rush the COVID vaccine and it
| probably saved millions.
|
| I don't understand why we can't let people make risk reward
| judgments. Yes probably more people will die, but they were
| not forced.
| inhumantsar wrote:
| I agree with you but I also understand the argument that
| being given the choice between certain death and uncertain
| death is a form of coercion
| fallingknife wrote:
| And I'm sure that those people dying are saying to
| themselves "well at least I wasn't coerced"
| lucianbr wrote:
| 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.
| torstenvl wrote:
| I agree. Dying in anguish at the hands of your own
| government is far worse than dying having tried everything
| you could.
| EatingWithForks wrote:
| 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.
| EA-3167 wrote:
| 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.
| causality0 wrote:
| 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?
| civilitty wrote:
| _> 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.
| thedragonline wrote:
| 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_.
| EA-3167 wrote:
| 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.
| EA-3167 wrote:
| 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.
|
| There is a difference in kind.
| causality0 wrote:
| _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.
| EA-3167 wrote:
| 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.
| tux3 wrote:
| 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.)
| haldujai wrote:
| 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.
| tux3 wrote:
| 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.
| haldujai wrote:
| > 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.
| tux3 wrote:
| 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.
| haldujai wrote:
| 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.
| tux3 wrote:
| 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.
| haldujai wrote:
| 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.
| tux3 wrote:
| Thank you. I really appreciate your patience and your
| careful replies, as well.
| haldujai wrote:
| 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.
| sleight42 wrote:
| Just "invest more"?
|
| Who does the investing? Not "The Market". The incentive isn't
| to cure but to treat. The Market wants (repeat) customers.
|
| The government? At least, in the US, we've been dismantling
| the government's ability to do this since at least Reagan.
| Even our so-called Liberals aren't pushing hard here. You'd
| have to look to the "fringe" Progressives within the
| Democratic Party to even come close.
|
| And why? Because "fuck you, I've got mine" may as well be the
| national motto of the USA at this point.
|
| People will bristle at this, certainly. Look at Biden: he's
| done so much!
|
| Biden is no FDR. We need a real social safety net in this
| country. And, yes, we need a "right to try", even if it means
| waiving malpractice rights in those cases.
| nine_k wrote:
| 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.
| GuB-42 wrote:
| > 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.
| sleight42 wrote:
| Vaccines aren't a cure. They require repeat customers.
| You're making my argument for me.
| haldujai wrote:
| Most vaccines only require 1-3 injections.
|
| 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.
| haldujai wrote:
| 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.
| User23 wrote:
| Gilead's hepatitis cure is a real example of this[1], so
| it's not some hypothetical. The sales plummeted and wall
| street dinged them for it.
|
| [1] https://www.investors.com/news/technology/can-gilead-
| withsta...
| GuB-42 wrote:
| Just read the article until the end.
|
| > 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.
| haldujai wrote:
| 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.
| thrashh wrote:
| Is there really a growing sentiment?
|
| If you have a system without problems, I'd be more worried.
|
| Edge cases like OP's can't be solved by any system. All systems
| have problems with things falling through the cracks.
|
| That's why lobbying exists. So people like OP can bring
| attention to a specific problem and lobby for it.
|
| Taking about changing the system is missing the point.
| lr4444lr wrote:
| 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.
| robbintt wrote:
| 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.
| adrr wrote:
| 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.
| [deleted]
| zaroth wrote:
| Clinical trials are, I think _always_ , free for the
| patient. The company developing the drug foots the bill.
| peyton wrote:
| That's just not true.
| DennisP wrote:
| Not always, but it's usually true.
|
| > 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.
|
| https://www.mskcc.org/cancer-care/clinical-
| trials/frequently...
| duxup wrote:
| One issue is, who pays for it?
|
| Experimental treatments often are very expensive, I believe
| require a lot of study of the patient and so on ...
|
| It's not like a magical pill(s) you take an go home and live or
| don't and everyone says "well he consented so he took his
| chances". The entire process of experimental treatments is
| hugely expensive.
| chroma wrote:
| For those who are curious, the term was coined on this blog
| post[1]:
|
| > The Copenhagen Interpretation of quantum mechanics says that
| you can have a particle spinning clockwise and counterclockwise
| at the same time - until you look at it, at which point it
| definitely becomes one or the other. The theory claims that
| observing reality fundamentally changes it.
|
| > The Copenhagen Interpretation of Ethics says that when you
| observe or interact with a problem in any way, you can be
| blamed for it. At the very least, you are to blame for not
| doing more. Even if you don't make the problem worse, even if
| you make it slightly better, the ethical burden of the problem
| falls on you as soon as you observe it. In particular, if you
| interact with a problem and benefit from it, you are a complete
| monster. I don't subscribe to this school of thought, but it
| seems pretty popular.
|
| The post provides real life examples of government programs,
| nonprofits, and individuals being criticized for helping in the
| "wrong" way.
|
| 1.
| https://web.archive.org/web/20210125231725/https://blog.jaib...
| noduerme wrote:
| 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?
| peteradio wrote:
| 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.
| unglaublich wrote:
| So, you would flip the railroad switch to kill only 1 instead
| of 5 helpless people?
| roflc0ptic wrote:
| the math checks out
| pjot wrote:
| MIT recreated this thought experiment to research the
| "morality" in autonomous vehicles.
|
| https://www.moralmachine.net/
| bandyaboot wrote:
| 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.
| dtech wrote:
| It explicitly states the passengers will be killed
| bandyaboot wrote:
| Never has my lack of attention to detail cost so many
| lives.
| lettergram wrote:
| 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.
| npsomaratna wrote:
| 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.
| [deleted]
| WalterBright wrote:
| Sam Peltzman goes into this and the statistics in his book
| Regulation of Pharmaceutical Innovation:
|
| https://www.amazon.com/Regulation-Pharmaceutical-Innovation-...
| agumonkey wrote:
| 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.
| alpineidyll3 wrote:
| 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.
| stared wrote:
| I call it Pontius Pilate's Ethics.
|
| It is (a very rational) approach for administrative workers,
| who get little credit for getting things better, but are at
| risk when they can be taken accountable for something terrible.
|
| That way, for example, in Germany, there was a halt on the
| Astra-Zeneca vaccine after a few cases of thrombosis per
| million. For comparison, it is one in six for COVID. The halt,
| most likely, caused many deaths. Yet, these deaths "have
| happened". If there were a death because an administrative
| organ didn't take action - the organ would be considered
| responsible.
|
| For the matter, Pontius Pilate was an administrative worker.
| And his incentives were aligned accordingly.
|
| In the language of the Trolley Problem, it is doing nothing (no
| matter how many are there on the tracks) or (even better)
| finding a way to pass the lever to someone else.
| yieldcrv wrote:
| > 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.
| blcknight wrote:
| Off label prescriptions are legal and very common.
| yieldcrv wrote:
| huh thats exactly what google says.
|
| 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
| batch12 wrote:
| > 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?
| y-curious wrote:
| 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?
| Kamq wrote:
| 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.
| abecedarius wrote:
| 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.
| Kamq wrote:
| > So what you're asking for is very not radical.
|
| Shame. Radical seems to be all the rage these days.
|
| Maybe I can brand it as radically conventional.
| devwastaken wrote:
| 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.
| ayewo wrote:
| Jake, even in the face of declining health, don't despair. I know
| it's difficult but please, don't lose hope.
| changoplatanero wrote:
| I get that the FDA is bad but how come there is no country
| anywhere on earth where these treatments are legal and available?
| etothepii wrote:
| 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.
| adventured wrote:
| 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.
| WarOnPrivacy wrote:
| > Why are medicines regulated federally? As I understand it
| (and IANAL) doctors, pharmacists and nurses are regulated on
| a state by state basis.
|
| Dr's typically practice in ~1 state while drugs are available
| in all states simultaneously.
|
| Fifty states - of varying ability - trying to independently
| qualify all available drugs would be a nightmare of
| redundancy.
| adventured wrote:
| Because the mRNA vaccine approach is just about as cutting edge
| as it gets right now and only a few countries on the planet are
| any good at it.
|
| The same is true for a lot of cutting edge treatments.
|
| It quite strictly limits where such treatments are likely to be
| available.
| Arainach wrote:
| 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.
| shuckles wrote:
| 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.
| qbrass wrote:
| 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.
| balls187 wrote:
| 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.
| A_D_E_P_T wrote:
| There's a very easy regulatory solution: Roll the drug approval
| process back to the way things were done prior to 1962. Back
| then, safety testing was all that was required. Efficacy testing
| -- which is difficult, expensive, arguably unethical in itself,
| and in some cases effectively impossible -- was not required.
| Drugs cost ~20-50x less to bring to market, and were brought to
| market faster. Indeed the 40s and 50s are still known as the
| pharmaceutical industry's "Golden Age." And it wasn't only
| because of low-hanging fruit.
|
| Pair this paradigm with extensive postmarketing surveillance and
| periodic reviews for efficacy in a patient population. These
| could be done at two years, five years, and eight years -- and
| approval automatically rescinded if safety issues arise or
| efficacy is close to null.
|
| Give people with fatal diseases a "right to try" drugs that
| haven't passed safety testing -- and use that data.
|
| Ban drug advertising in public-facing media.
|
| Simple as.
| nathan_compton wrote:
| Apparently there is already a Right to Try:
|
| https://www.fda.gov/patients/learn-about-expanded-access-and...
| sheeshkebab wrote:
| Get rid of prescription requirement too - who needs to see a
| doc for extra $500 when I can go and pick my own med, and
| possibly better one.
| tgv wrote:
| I remember Softenon.
|
| > it wasn't only because of low-hanging fruit.
|
| Yeah, right. They had such advanced cancer medication back
| then.
|
| > Give people with fatal diseases a "right to try" drugs that
| haven't passed safety testing -- and use that data.
|
| That data is practically worthless.
|
| I'm in favor of having people try out medication, but it will
| need to be heavily regulated. And we know what happens to
| regulation: a party comes along that doesn't like regulation,
| or gets bribed, and the regulation goes out the window. It's a
| good way to start another opium crisis.
| RangerScience wrote:
| My brother had an excellent metaphor:
|
| > Say you're a runner. In the beginning of your competitive
| career, you get the most gains by becoming a better runner.
| And then at some point, you get more gains by shooting (or
| bribing) the ref.
| A_D_E_P_T wrote:
| > "B-but Thalidomide!"
|
| This is the reflexive response to every common-sense proposal
| to roll back the regulatory burden.
|
| I'd raise a couple of points in response:
|
| First, Thalidomide was never approved in the USA -- for
| safety reasons. The mechanisms that were in place at the time
| did their job.
|
| Second, the response to Thalidomide was overblown and indeed
| downright hysterical. "Better to let 100,000 people die of
| neglect than allow one person to suffer an awful drug
| reaction" is not rational policy.
|
| > That data is practically worthless.
|
| Enough "practically" worthless data, and you get somewhere.
| It's a matter of quantity. Obtaining "hiqh quality" data is
| often unethical in medical practice.
| TheRealPomax wrote:
| The world "simple" is doing so much heavy lifting here, it
| might as well be written as ______ instead.
| throw9away6 wrote:
| I'm fine with that as long as insurance does not pay for any
| drugs without efficacy testing. Also no advertising of any
| sort.
| fnord77 wrote:
| insurance already gets away with not paying for some highly
| efficacious drugs, so I don't think this will be a problem
| sterlind wrote:
| generally, insurance companies do require efficacy. many of
| them have decided not to cover aducanumab for that very
| reason. though this also gives insurance an additional excuse
| to deny stratospherically-expensive gene therapies and other
| life-saving new treatments, since even the most effective new
| drugs won't have e.g. 10 year survival rates until they're a
| decade old.
|
| agreed on advertising though.
| indrora wrote:
| Ah yes, let's go back to the days of Thalidomide.
|
| For those that don't know, the 1962 change is the Kefauver-
| Harris Amendment, which was a response to one of, if not the,
| largest overall global crisis of conscience in the medical
| field. From Wikipedia: "When first released, thalidomide was
| promoted for anxiety, trouble sleeping, "tension", and morning
| sickness." After some time it became increasing obvious that
| while it worked, it caused birth defects in pregnant or soon to
| be pregnant women, with its manufacturers actively trying to
| quash the information about such cases; again, from Wikipedia:
| "Use of thalidomide in pregnancy can cause fetal abnormalities
| such as phocomelia (malformation of the limbs). In males who
| are taking the medication, contraception is essential if a
| partner could become pregnant."
|
| Thalidomide disfigurements were disturbing. Children born with
| these disfigurements were not linked to Thalidomide until much
| later. Thalidomide was in fact not allowed a safety regulation
| by the FDA initially. It wasn't until the company producing it,
| Grunenthal, 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. Grunenthal'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 Grunenthal 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".)
| pitaj wrote:
| Everything you said has absolutely nothing to do with what GP
| said.
| abecedarius wrote:
| None of that has anything to do with the proposal you're
| replying to, which is about the efficacy requirement, not
| safety.
| abecedarius wrote:
| It's far from a full solution, but it'd be progress.
| rebeccaskinner wrote:
| 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.
| pengaru wrote:
| According to wikipedia, many types of squamous cell carcinomas
| are associated with HPV infection. [0]
|
| Another area where the US has lagged which would prevent a lot of
| these cancers from ever developing in the first place is HPV
| vaccination. Last I heard it was only females who were being
| routinely vaccinated, and relatively recently at that. We should
| really be prioritizing eradication of HPV.
|
| [0]
| https://en.wikipedia.org/wiki/Squamous_cell_carcinoma#By_bod...
| gilbertmpanga12 wrote:
| [dead]
| Sinidir wrote:
| Must feel especially shitty to have your freedom curtailed like
| this, looking at the probable end of your life.
| tb_technical wrote:
| 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?!
| YZF wrote:
| 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.
| dashmeet wrote:
| 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
| m3kw9 wrote:
| 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
| anjel wrote:
| 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.
| tekla wrote:
| > USA rubber stamps probably safe food items. Europe goes WTF
| how dare they think its safe.
|
| > USA refuses to accept rubber stamp European experimental
| medication. Europe _pikachu face_
| LordShredda wrote:
| Because they might make mistakes? See: thalidomide
| Latty wrote:
| 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.
| maxbond wrote:
| Thalidomide was widely approved, and I'm glad the FDA didn't
| rubber stamp it.
| arrosenberg wrote:
| 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.
| wbl wrote:
| The FDA can approve a new drug in under a year as we saw with
| covid vaccines. Every time an effective drug is made and they
| don't people die waiting.
| maxbond wrote:
| 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.
| wbl wrote:
| Why doesn't it mean that?
| maxbond wrote:
| 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.
| wbl wrote:
| 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.
| maxbond wrote:
| > If this is a resource problem then the case for
| increasing the budget is clear.
|
| Agreed.
| theflyingelvis wrote:
| I take a derivative, Lenalidomide, for cancer maintenance. I
| am very glad the FDA approved it.
| chroma wrote:
| 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.
| maxbond wrote:
| 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.
| dghughes wrote:
| > thalidomide, a deadly and basically worthless
| medication,
|
| Thalidomide is what is used to treat erythema nodosum
| leprosum (ENL) better known as just leprosy.
| morelisp wrote:
| It's not been recommended in decades.
| maxbond wrote:
| 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."
| nradov wrote:
| [flagged]
| [deleted]
| tux3 wrote:
| 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).
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413435/
| chroma wrote:
| 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.
|
| 1. https://www.nytimes.com/1982/02/02/science/new-class-
| of-drug...
| maxbond wrote:
| It's one thing to say they should approve drugs faster
| and another thing to say they should rubber stamp
| anything that Europe and Canada approve.
| chroma wrote:
| 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.
|
| 1. https://astralcodexten.substack.com/p/adumbrations-of-
| aducan...
| maxbond wrote:
| 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.
| chroma wrote:
| 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.
| maxbond wrote:
| 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.
| chroma wrote:
| 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.
| maxbond wrote:
| > Your response to _any_ criticism of the FDA or _any_
| proposed fix is to say that we need to make the FDA more
| competent... [Emphasis added]
|
| You've only proposed one fix. I'm only opposed to one
| idea.
|
| You aren't under any obligation to try and convince me of
| anything, but surely you don't have to put words into my
| mouth.
| chroma wrote:
| What hypothetical evidence would cause you to change your
| mind about allowing American doctors to prescribe drugs
| approved by the EU?
| maxbond wrote:
| 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.
| [deleted]
| Glawen wrote:
| 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
| baggy_trough wrote:
| Sounds great, where do I sign up?
| YZF wrote:
| 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).
| dkasper wrote:
| 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.
| [deleted]
| gabea wrote:
| 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?
| Google234 wrote:
| 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
| banana_feather wrote:
| 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.
| amanaplanacanal wrote:
| It appears that he is in New York, which doesn't have a right
| to try law on the books.
| arbuge wrote:
| If that is the reason, perhaps temporarily moving to another
| state might help? The author appears to still be mobile.
| codexjourneys wrote:
| Absolutely, the closest state to NY with a "right to try"
| law is Connecticut. Pennsylvania also has one.
| https://righttotry.org/in-your-state/
|
| Edit: Also, the federal law applies regardless of location:
| https://righttotry.org/rtt-faq/
|
| "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."
| [deleted]
| abhaynayar wrote:
| 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.
| skilled wrote:
| Why'd you be so pessimistic when there's plenty of evidence
| that there is.
|
| Or are you saying that billions of Buddhists and Hinduists are
| delusional?
| learplant wrote:
| It's not that they are delusional, it's that they can't prove
| it. They don't have evidence, they have faith.
| hattmall wrote:
| Oh, you know, it's just someone that thinks everyone except
| them is wrong!
| skilled wrote:
| Doesn't really add anything to the conversation though
| jacquesm wrote:
| 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.
| m3kw9 wrote:
| We all find out
| swayvil wrote:
| Our salvation is in psychedelic drugs. I'm serious.
|
| There is no cheaper way to turn swine into gentlemen.
|
| Now we just need to trick them into eating the stuff.
| kortex wrote:
| 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.
| I_Byte wrote:
| 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.
| kortex wrote:
| 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,
| scoofy wrote:
| 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.
| HPMOR wrote:
| 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.
| scoofy wrote:
| 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.
| jacquesm wrote:
| > I DO NOT want the cessation of experience.
|
| 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.
| abhaynayar wrote:
| 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.
| scoofy wrote:
| 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.
| colordrops wrote:
| I'm not scared of death. I'm scared of an extended painful
| exit.
| grrdotcloud wrote:
| 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?
| [deleted]
| woodpanel wrote:
| 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.
| dr_dshiv wrote:
| I really sympathize with the author and feel his position has
| great moral clarity.
|
| Wish there was some country or state where you could try more
| freely.
| [deleted]
| HWR_14 wrote:
| I would hate to ask the author this, as it seems cruel, but is
| the FDA denying him access? As he points out, Moderna has two
| drug trials going. The FDA "right to try" page[0] clearly spells
| out that Moderna _could_ give him unproven medicine currently in
| a clinical trial under the right to try laws. So Moderna could
| let him into one of the two studies, or give him the medicine
| under the right to try laws if it rejects him.
|
| Likely, Moderna doesn't want him to take the drugs because they
| will probably be ineffective this late in the cancer stage. It
| doesn't want its treatment to be associated with his death.
|
| [0]https://www.fda.gov/patients/learn-about-expanded-access-
| and...
| adamredwoods wrote:
| I believe the oncologist has to present the case to Moderna for
| use. If insurance is involved, insurance will deny it.
| CogitoCogito wrote:
| 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.
| haldujai wrote:
| 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.
| HWR_14 wrote:
| 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.
| haldujai wrote:
| 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.
| adamredwoods wrote:
| For the record, FDA has fast track / breakthrough therapy
| options:
|
| https://www.fda.gov/patients/learn-about-drug-and-device-app...
|
| Biden's Moonshot program is trying to drive money to support new
| innovations:
|
| https://www.whitehouse.gov/cancermoonshot/
| pstuart wrote:
| This could change if there was enough political pressure. Easier
| said then done, but it should be done.
| jstummbillig wrote:
| This seems bad. Help me understand.
|
| In what ways does _always_ letting individuals choose to take an
| experimental drug not work, if we make sure they know what is
| known and what is not? They are desperate, and that 's a horrible
| place from where to make a decision, but dying is a really bad
| alternative.
|
| What are the pitfalls that would allow for this to not always be
| the option? How would this go more horribly wrong than just
| letting these people die?
| HWR_14 wrote:
| 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.
| jstummbillig wrote:
| 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.
| HWR_14 wrote:
| 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.
| tlb wrote:
| 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.
| [deleted]
| dghughes wrote:
| 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.
| adamredwoods wrote:
| I don't think the metformin trials prove much, but I agree, it
| could have been worth a try.
|
| In moments like this, I think it is appropriate to find a
| second opinion, sometimes just to attempt something new.
| anonuser123456 wrote:
| >My Dad's doctor wouldn't even discuss it and dismissed it
| outright.
|
| Given metformins safety and cost profile, your dads doctor
| sucked. They should put it in the water of the 60+ crowd.
| serial_dev wrote:
| Anecdotal. When "quack" * science helped.
|
| After COVID (both the disease and the vaxx), I got heart
| arrhythmia, I had around 5000 irregular heart beats a day (PVCs
| and PACs mainly), and those all happen in a matter of hours, so
| when they happen, it's pretty debilitating.
|
| After a while, I invested in a Bluetooth stethoscope and ECG
| watches, the doctors finally believed I have something.
| However, the cardiologist's advice was to learn to live with
| it, because it's completely harmless and in young people,
| ablation, beta blockers are not worth the risk.
|
| Having these irregular heart beats is a very uncomfortable
| feeling, so I was looking for articles about the root causes
| and potential treatments.
|
| After trying a couple of things (both pills and lifestyle
| changes), I found an article that says arginine and taurine
| reduced the number of irregular heart beats in their
| experiment. I tried it out and I have basically 20-50 irregular
| heart beats a day. When I stop taking them, the irregular heart
| beats come back.
|
| Now, I know I'm doing something that is potentially risky, but
| to me it is worth it (and I reduced my dosage, and I try to
| quit using them every couple of months).
|
| * it's not really quack science as the science is real, just
| that me applying it in my situation was not recommended by a
| doctor
| datori wrote:
| 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.
| user_7832 wrote:
| I wonder - both in this specific case, and in general - if anyone
| here on HN has enough media/political reach to spread this
| message.
|
| This case reminds me a lot of the FAA realizing that safety
| restrictions for toddlers would _increase_ deaths as more people
| would drive.
| (https://www.ntsb.gov/news/events/Documents/child_safety-Clau...,
| https://www.ucsf.edu/news/2003/10/97119/airline-infant-safet...)
| latchkey wrote:
| If we block someones ability to try novel procedures, how is that
| any different from blocking their right to assisted suicide?
| amelius wrote:
| Because access to novel procedures gives us valuable data.
| lr4444lr wrote:
| 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.
| kif wrote:
| I think guaranteed death is much more different than potential
| death and potential cure.
|
| It's a tough line to walk on, still.
| latchkey wrote:
| The only guarantee in life, is death.
| _Algernon_ wrote:
| ...and taxes.
| tekla wrote:
| The difference is in how painful and how long that death
| will be
| zer8k wrote:
| But we allow physician assisted suicide.
|
| Strange isn't it? Almost sounds like soylent green. Maybe I'll
| skip McDonald's this week.
| [deleted]
| eilertokyo wrote:
| 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.
| abecedarius wrote:
| 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.
| balls187 wrote:
| 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.
| kepler1 wrote:
| 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.
| jojobaskins wrote:
| 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...
| tpmoney wrote:
| >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.
| sam537 wrote:
| You should also try immunotherapy (pembrolizumab) with chemo if
| your CPS is >1% before experimental early phase trials.
| technick wrote:
| 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.
| A_D_E_P_T wrote:
| > 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.)
| [deleted]
| prmoustache wrote:
| 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.
| janeway wrote:
| 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.
| peter422 wrote:
| 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.
| timmytokyo wrote:
| 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%.
| Arainach wrote:
| The probability of a more painful death is also greater than
| 0%. So it the probability that something could go wrong and
| cause publicity which would interfere with the testing or
| approval of the drug and affect other people's access in the
| future*. There are always tradeoffs.
|
| *this person takes the drug. Two days later they die of a
| heart attack. Was it caused by the drug? How many resources
| should be spent to determine that? Should that death be
| listed in the potential side effects? What if the news story
| publishes an article and scares people off from the trial?
| What if it's later proven that the drug had no effect on the
| heart attack but the distraction from it delayed 10,000
| people's access to the drug?
|
| The world is complicated.
| Dylan16807 wrote:
| The heart attack thing isn't a tradeoff. Whether they test
| now or test later it has basically the same chance of
| happening.
| mft_ wrote:
| > 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.
| HWR_14 wrote:
| In serious (esp. life-threatening) situations, the placebo is,
| or is supplemented with, the normal course of medicine, not
| sugar water.
| prmoustache wrote:
| Butnot habing access to normal course of medicine is not what
| the author is complaining about
| Nifty3929 wrote:
| The greater good argument is repugnant in this case. He is
| going to die, and deserves an opportunity to do whatever is
| possible to save himself, including new and little-tested, and
| likely ineffective treatments. He literally had nothings to
| lose.
|
| And in this case he would be actively helping humanity as well
| by being a test case. We would all gain knowledges and
| information from his treatment, if he could get it.
|
| This policy hurts all of us.
| sgseliger23 wrote:
| This is my brother. I love you.
|
| Anyone who has suffered through this disease or has a loved one
| that experienced it knows the feeling of helplessness.
|
| More on Jake's story below, and a link to the fundraiser to
| support him and his wife: https://www.gofundme.com/f/help-the-
| fight-against-cancer-wit...
|
| Be kind and good to your loved ones. Life is short and no one
| knows how much time we have left. While the FDA's antiquated
| bureaucracy does no good, the true enemy is the disease itself. I
| believe in science and I hope that someday no one else will
| needlessly suffer as my brother has.
|
| You be good. I love you.
| Mizoguchi wrote:
| 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.
| thumbuddy wrote:
| This is the real reminder for young people. Every single one of
| us is one tiny cellular mishap away from an untreatable,
| agonizing demise. Be KIND to one another, because when it is
| your turn to die, you will have wanted to have had a positive
| impact on the world and those around you.
|
| Stabbing backs to maybe get a pay raise will mean nothing to
| you or your family. It's just one more person who won't honor
| your temporary existence.
|
| Be KIND.
| ayewo wrote:
| The surname is very familiar. I checked and Jake is in fact a
| long-standing member of this community as jseliger [1].
|
| I'm sorry for the very difficult times your brother is going
| through. I hope and pray that his situation improves.
|
| 1: https://news.ycombinator.com/user?id=jseliger
| croisillon wrote:
| more specifically, this topic has been brought here
| https://news.ycombinator.com/item?id=36393383
| sam2426679 wrote:
| I'm sorry this is happening to you. Thank you for fighting to
| improve SCC outcomes for yourself and others. Please keep us
| updated with your progress.
| gburt wrote:
| Regulators are, in general, too sheltered and disconnected from
| the impact of their actions.
|
| Incentives matter. When you get to make decisions that impact
| others, but not feel any of the costs associated with that, you
| do not have the correct incentives. I hope the staff of FDA read
| this and can't sleep tonight. We can hope they feel some
| emotional pain, even if it is only some small subset of the pain
| they have and continue to cause to others.
|
| _FDA delenda est._
| janeway wrote:
| 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.
| gburt wrote:
| 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.
| Arainach wrote:
| 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
| gburt wrote:
| 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.
| ilamont wrote:
| How horrible and frustrating. There is a fast-track approval
| procedure described here, I wonder why it doesn't apply to these
| treatments?
|
| https://www.fda.gov/patients/fast-track-breakthrough-therapy...
|
| There is some important context for the following comment:
|
| _"If anything goes wrong," he argued, "think how bad it will
| look that we approved the drug so quickly."_
|
| In the 1980s, when the comment was made, there were still people
| at the FDA who remembered the Thalidomide disaster, which would
| have been a lot worse had the FDA approved the drug. In the U.S.
| several thousand women took thalidomide during the clinical
| trials, and some doctors took it, too:
|
| _In one case, a doctor had been using thalidomide himself and
| prescribing it to his wife. In addition to the wife's loss of
| vision, the doctor mentioned peripheral neuritis, nerve pain that
| is a side effect of thalidomide.
|
| The other report is even more alarming -- a nurse had given birth
| to a baby without arms or legs and, as a registered nurse, "she
| may have had access to the item."_ (1)
|
| Other countries including Canada, Taiwan, Japan, and West Germany
| _did_ approve the drug or allowed it to be sold.
|
| _On December 2 1961, the drug was taken of the German and
| British markets, after several doctors brought up concerns as it
| appeared more and more plausible that thalidomide, when taken by
| pregnant women, was responsible for severe birth defects. Thought
| the Government of Canada was informed of these suspicions about
| the possible teratogenic effects of thalidomide, we had to wait
| until March 2 1962 for the Canadian authorities to react and, in
| their turn, withdraw thalidomide from the market. As unbelievable
| as it can appear, thalidomide was legally available in Canada for
| three full months after being withdrawn from its origin country._
| (2)
|
| 1. https://www.nytimes.com/2020/03/23/health/thalidomide-fda-
| do...
|
| 2. https://thalidomide.ca/en/the-canadian-tragedy/
| [deleted]
| oaktrout wrote:
| Hopefully he makes it into a clinical trial. In case anyone is
| interested in reading what trial options are available for this
| type of cancer you can find the trials here:
| https://www.clinicaltrials.gov/search?cond=Squamous%20Cell%2...
| HWR_14 wrote:
| 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.
| youssefabdelm wrote:
| There was a drug called Rapamycin discussed in this Radiolab
| episode https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub
|
| The drug supposedly helped delay the doctor's cancer and extend
| his lifespan until he stopped taking it, then it came back "with
| a vengeance" and he passed away. He wanted to stop taking it to
| verify whether it was actually working or not.
|
| I wonder if it might help this person? He might have to be on it
| for life though.
|
| Don't take my word for it though, this is FAR from my field of
| expertise.
| adamredwoods wrote:
| This is an mTOR inhibitor, I believe there are others already
| in clinical trials. I know PIK3 inhibitors are used to block
| some cancers. Most inhibitors stop cancer for "a while" but
| cancer cells have the ability to circumvent pathway
| disruptions.
|
| https://en.wikipedia.org/wiki/Sirolimus
|
| https://en.wikipedia.org/wiki/MTOR_inhibitors
| xk_id wrote:
| PI3K inhibitors only work if the tumour tests positive for
| that special mutation.
| donall wrote:
| 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!]
| nradov wrote:
| 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.
| strangescript wrote:
| 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".
| baggy_trough wrote:
| [flagged]
| can16358p wrote:
| Couldn't agree more. There is literally nothing to lose, and
| potential to save a life.
|
| Blocking this is effectively murder.
| CogitoCogito wrote:
| 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.
| bruce343434 wrote:
| ...why?
| baggy_trough wrote:
| [flagged]
| bruce343434 wrote:
| You are enabling quack doctors
| baggy_trough wrote:
| You are killing people under the guise of helping them.
| kortex wrote:
| 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.
| dang wrote:
| 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.
|
| If you wouldn't mind reviewing
| https://news.ycombinator.com/newsguidelines.html and
| taking the intended spirit of the site more to heart,
| we'd be grateful.
| xk_id wrote:
| Holy christ how did AI make it even in this conversation!?!
| [deleted]
| rdl wrote:
| 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.
| denhaus wrote:
| two questions:
|
| - where do you go, and why?
|
| - how do you get your US insurance to cover/work with providers
| outside the US? does it just automatically work or...?
| rdl wrote:
| 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/departmen
| ts/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.)
| balls187 wrote:
| I don't know why, but this was heart breaking to read. I don't
| think it was meant to be.
| olliej wrote:
| 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.
| orzig wrote:
| Read the rest of his blog; it's wonderful and I'm devastated that
| someone I followed for years is going to vanish.
|
| Thank you for giving us all some of your time on this earth.
| jbullock35 wrote:
| Highly relevant: research on ways to accelerate the medical-trial
| process. Here is one example from JASA:
| https://doi.org/10.1198/016214504000001790.
| kepler1 wrote:
| 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.
| robomartin wrote:
| Trump got a federal Right to Try experimental drugs act passed in
| 2018:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309195/
|
| Not sure how this intersects with the author's reality. It is sad
| to see article after article spewing nothing but hatred towards
| Trump --almost purely from an ideological perspective-- when
| something like this could help so many.
|
| This, in more ways than one, demonstrates how difficult of a
| problem this is. When people's lives become game pieces in
| political battles, the people lose and politicians, well, use
| them to score points towards their own career objectives.
|
| I read in a comment that the author lives in NY, where,
| apparently, Right to Try isn't available. If find this
| interesting when a federal law has been in place since 2018.
|
| This is one of the things that can be perplexing about the US
| system of government. Here we have a state preventing people from
| having access to treatments that could materially affect their
| illness when federal laws allow it.
|
| While I do understand the many advantages of the independence
| granted to states by the US constitution, sometimes it feels like
| the US has devolved into a fifty regions pretending to be united
| as a nation when they are actually not and, as a result, end-up
| conspiring to damage the very societies they claim to protect.
|
| Education is another example of this. All nations with excellent
| systems of education (and the results to prove it) have national-
| level planning, management and standards. In the US, not only is
| our system of education fragmented at the State level. Our
| schools are run by fucking unions organized as districts, each
| with their own axe to grind. It is no surprise the results are
| what they are.
|
| We somehow manage to extend some of this "excellence" (sarcasm)
| into every level of healthcare.
| snitty wrote:
| 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.
| [deleted]
| light_hue_1 wrote:
| Blaming the FDA is popular but the problem is not the FDA itself.
| Drug manufacturers are part of the problem.
|
| 1. When the FDA has fast-tracked drugs, drug makers have taken
| advantage of this to hide data, lie, and refuse to comply with
| timelines for proving those drugs work.
| https://www.npr.org/sections/health-shots/2022/07/22/1110830...
|
| 2. When these accelerated drugs are found to not work or cause
| harm, the manufacturers continue to push for them and the FDA has
| tremendous trouble trying to their approval revoked.
| https://apnews.com/article/science-health-medication-busines...
|
| 3. Accelerated drug approval gets mired in advertising. The
| general public has no idea how to judge if a drug works or not.
| Plenty of people believe that homeopathy works. The FDA gets
| massive pushback when trying to take a drug that is worthless
| away, because people think it works. This hurts us all and
| creates an incentive for companies to hide data and deceive
| customers.
|
| 4. The FDA is as fast or faster than the Canadian or EU
| equivalents. The FDA is not specifically slow, bureaucracy
| everywhere has become much slower because there are no incentives
| to be fast but countless incentives to be slow.
|
| 5. Lawsuits. It's easy to say "I'm hurting, I'll take anything".
| But, then, there are rights you cannot give away. If a drug harms
| you, you will sue. If it kills you, your family will sue. The
| whole system is bogged down by lawsuits with massive
| disproportionate payouts. The early biotech companies and
| scientists involved often cannot deal with even a mistaken
| lawsuit.
|
| We need a much more comprehensive overhaul of the system,
| starting with open access laws to all data pertaining to any
| drugs that are on the market (no manufacturer can keep anything
| secret for a drug that people take), an FDA that has much more
| authority and much less industry capture, medical tort reform, to
| create a system where in exchange it actually makes sense to
| provide fast tracked approval.
| zer8k wrote:
| 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.
| light_hue_1 wrote:
| Huh? I literally said that.
|
| But that's not the main problem here. You would expect the
| FDA to approve everything by that theory.
| foobarbecue wrote:
| 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
| kortex wrote:
| Why don't we just have a schedule/tier system?
|
| Category A - approved by the FDA, basically what we have right
| now
|
| Category B - approved by some other established regulatory body
| (EU). Comes with all the warnings, doctors can write it off-
| label, insurance companies may not cover it but doctors can ask
| for a variance
|
| Category C - approved by some non-OECD body. Insurance companies
| under no obligation to cover
|
| Category D - experimental, this is stuff maybe still only in
| animal models, but pharmacies can still order and dispense it
|
| Category E - experimental and basically limited run from
| pharmaceutical companies. These essentially need to be tailor-
| made or produced by a GMP kilo lab. There are plenty of drugs in
| this category - I worked on them - and the intended recipients
| are entirely animals, QA, and regulatory agencies. But maybe if
| some crazy S.R. Hadden type (billionaire in Contact) wants to
| guinea pig themselves, let em.
|
| The latter category also opens the door for custom therapies
| (gene/mRNA) that you basically can't test the active
| pharmaceutical ingredient for efficacy on.
| haldujai wrote:
| > 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.
| porejide wrote:
| > This sounds like a recipe for killing people.
|
| Do you know what else sounds like a recipe for killing
| people? Not allowing people to access therapeutics that might
| save their life because it hasn't yet gone through regulatory
| approval yet for whatever reason (delays, too expensive to
| submit), etc.
|
| > There's very little that's approved by a non-US body and
| approved by the EU or non-OECD body that warrants clinical
| use, and if it is it gets reviewed quickly
|
| LOL. What are you talking about. There are so many examples.
|
| One of the most tragic is amisulpride. Amisulpride is an
| antipsychotic medication used to treat schizophrenia and
| other psychiatric conditions. Some key notes about its
| regulatory status:
|
| - Amisulpride was first approved in France in the 1980s and
| is widely used in Europe.
|
| - It was never approved by the FDA for use in the United
| States, and at this point there's not organization that can
| afford to go through the approval process because there's no
| patent.
|
| - The reason often cited is that the manufacturer did not
| apply for approval with the FDA. It was likely not considered
| commercially viable for the US market at the time.
|
| - Amisulpride is believed to have comparable efficacy to
| other second-generation antipsychotics like olanzapine and
| risperidone, but with a lower side effect burden according to
| some studies.
|
| - In Europe, amisulpride is considered a first-line treatment
| option for schizophrenia, but American psychiatrists do not
| have access to it. According to some sources, it is literally
| recommended as the best antipsychotic in other countries.
| abeppu wrote:
| > 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."
| haldujai wrote:
| > 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.
| haldujai wrote:
| > 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).
|
| [0] https://www.cochranelibrary.com/cdsr/doi/10.1002/146518
| 58.CD...
| porejide wrote:
| The issue with antipsychotics tends to be the side
| effects, not the efficacy
|
| Amisulpride, for a lot of people, would be one of the
| best antipsychotics.
|
| Antipsychotics are incredibly important medications for a
| lot of people. It really matters that amisulpride is not
| available.
|
| https://psychnews.psychiatryonline.org/doi/full/10.1176/a
| ppi...
|
| "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."
| haldujai wrote:
| > 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.
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