[HN Gopher] When dying patients want unproven drugs
       ___________________________________________________________________
        
       When dying patients want unproven drugs
        
       Author : jseliger
       Score  : 82 points
       Date   : 2023-06-19 16:52 UTC (6 hours ago)
        
 (HTM) web link (www.newyorker.com)
 (TXT) w3m dump (www.newyorker.com)
        
       | Havoc wrote:
       | Sure. If we've got to test dangerous drugs on humans (which at
       | some point you must) - this is about as ethical as it gets I
       | think.
        
       | renewiltord wrote:
       | We appointed gatekeepers and gave them a gate. Now they keep the
       | gate, though our salvation is on the other side. It is the nature
       | of gatekeepers to keep gates. So we perish, our gates well-kept.
        
         | tdeck wrote:
         | The other side of the gate is Tijuana where you can spend your
         | family's life savings to die in a clinic offering some quack
         | treatment.
        
           | renewiltord wrote:
           | Haha, for others. Not for me. I do not constrain myself to
           | the law even here in the US, so I'm okay.
        
       | mynonameaccount wrote:
       | What else do they have to lose? The problem with the US health
       | care system is that everything is reliant on a medical
       | professional. Want a blood test, a medical professional has
       | generate it. Want a ultrasound, go to a medical professional
       | first. I am in charge of my health. I don't need no stinking
       | doctor who could give a shit what happens to me. They get paid no
       | matter. I should be able to schedule and pay for a full body scan
       | if I want.
        
         | pookah wrote:
         | [dead]
        
         | juve1996 wrote:
         | No, the problem is cost. The medical professional part is
         | secondary because no one wants to pay for hypochondriacs who
         | think their cough at 25 is stage 4 lung cancer based on webMD
         | research, because getting a full body scan is expensive. If it
         | was cheap then it wouldn't matter.
        
       | lacker wrote:
       | It seems like there's a lot of lower hanging fruit here. For
       | example, we could let people in the US take any drug that has
       | been approved in any of the EU, England, Canada, or Japan. A drug
       | isn't really "unproven" if one of the world's top-tier medical
       | establishments approves it.
       | 
       | The core problem is that our current drug approval process is
       | slow, expensive, and risk-averse. The medical establishment seems
       | very inward-focused, ignoring what happens in other countries,
       | even the countries that are just about as sophisticated as we
       | are.
        
         | tdeck wrote:
         | I'm not sure what the ultimate cost/benefit to this proposal
         | would be, but it's worth noting that thalidomide was approved
         | in many other countries but not the US.
        
         | hinkley wrote:
         | I've forgotten what drug but I recall a lot of people being
         | salty about five years back because there was a much more
         | effective treatment in Europe for some chronic condition and
         | the ETA for FDA approval was still multiple years. It's not
         | often such a large time lag that but sometimes the deck gets
         | stacked against you.
        
         | H8crilA wrote:
         | While you're at it please import the European payments system.
         | I was laughing when I heard that bank account number (or some
         | other number associated with the account, not sure about the
         | name) is secret. Switch to IBAN today! IBANs are public, and
         | payments between them usually cost significantly less than $1.
         | In some bad cases $5.
        
           | richiebful1 wrote:
           | Secret? Bank account numbers are written on the bottom of
           | personal checks
        
         | Spivak wrote:
         | I like this a lot and it would end my importing the good
         | sunscreen from Europe because the FDA is reeeeeally slow.
        
           | H8crilA wrote:
           | Are you sure it's good sunscreen, and not just a lie about
           | the SPF? There have been many of those around the world,
           | stuff that's N sold as 1.5*N.
        
             | Spivak wrote:
             | What I get is La Roche-Posay Anthelios UVmune 400 Invisible
             | Fluid. The American version doesn't protect as much against
             | UVA because the new fancy filters haven't been approved by
             | the FDA yet.
        
               | Topfi wrote:
               | A great choice, my favorite for daily wear, but Anthelios
               | is basically sold everywhere over here.
               | 
               | I have no dog in this fight, especially because as
               | someone who often finds themselves defending EU
               | regulations to people who grew up in the States, but I
               | have a hard time following why the FDA appears to drag
               | their heels on approving more advanced filters, whilst
               | Australian, South Korean and EU regulators are all far
               | quicker. Do these three major jurisdictions with
               | historically the highest standards for sunscreens have
               | more streamlined processes, are they willing to take more
               | risks, is the FDA simply underfunded to handle
               | throughput?
               | 
               | It's especially odd considering other parts of FDA
               | approval can often feel overly fast compared to other the
               | regulators jurisdictions, especially when it comes to
               | approving medical devices[0].
               | 
               | [0] https://www.tctmd.com/news/medical-devices-cleared-
               | faulty-pr...
        
             | [deleted]
        
       | 908B64B197 wrote:
       | Isn't the answer simply: My body my choice?
        
         | paxys wrote:
         | Do you agree with the existence of the FDA at all then? Their
         | entire job is to tell you what you can or cannot put in your
         | body.
        
           | randyrand wrote:
           | I thought it was primarily to ensure standardized testing,
           | labeling, etc.
        
           | JimtheCoder wrote:
           | "Their entire job is to tell you what you can or cannot put
           | in your body."
           | 
           | Isn't their job to tell businesses what they can or cannot
           | sell to you to put in your body? Sorta different...
        
             | paxys wrote:
             | And in this case they are telling a drug company that they
             | cannot sell an unapproved drug. Are you okay with that?
        
               | JimtheCoder wrote:
               | I'm not a fan of the FDA at all and the current clinical
               | trial process. I was just commenting that I thought your
               | statement as to what their responsibility was is
               | incorrect.
        
               | hanniabu wrote:
               | Offer it for free, problem solved
        
               | JimtheCoder wrote:
               | How many pages would that legal liability waiver have to
               | be...
        
           | derefr wrote:
           | Technically, the FDA regulates precisely one thing:
           | labelling. They regulate what can be _marketed as_ a name
           | with a conventional meaning ( "cheese" or "beef") or what
           | claims can be made about a product in its marketing ("treats
           | headaches", etc.)
           | 
           | The FDA audit for adulteration because e.g. "beef with high
           | levels of thyroid hormone in it" isn't what people expect to
           | be getting if they buy something called "beef." If you _label
           | the product as_ "beef with high levels of thyroid hormone in
           | it", then it's fine! (Same reason "Cheez Whiz" isn't legally
           | able to market itself as "cheese" -- it doesn't contain what
           | people expect "cheese" to conventionally contain.)
           | 
           | The FDA audit for drug safety and efficacy because you can't
           | say "makes your headache go away" if it actually doesn't; and
           | you can't _leave out_ "causes cancer in 1/10th of people who
           | take it" if it _does_. (And for a novel substance, you can 't
           | know _what_ claims you 're able to make or leave out, without
           | first doing a trial; so any claims you make are considered
           | invalid by default without such a trial.)
           | 
           | If you don't make any claims, you don't have to prove safety
           | or efficacy. Supplements are just drugs that don't make any
           | claims.
           | 
           | This is also why there are products on the market that
           | contain the active ingredients of prescription-only drugs,
           | but are freely purchasable -- these aren't _marketed as
           | being_ for human consumption. (GBL, a recreational drug
           | related to GHB, is sold on the open market as a  "brake-drum
           | cleaning fluid." And it actually _does work_ as a brake-drum
           | cleaning fluid, so it 's not like the FDA can challenge
           | that.)
           | 
           | If you're wondering about making drugs illegal: the FDA
           | doesn't (and can't) do that. The DEA does that.
           | 
           | If you're wondering about making drugs "controlled
           | substances": Congress does that. Then the DEA and the FDA
           | both enforce those rules -- the DEA by preventing
           | importation; and the FDA by preventing drugs from being
           | marketed for sale that contain that active ingredient --
           | basically treating it as an adulterant regardless of
           | labelling. (Note that these are both _commercial trade_
           | activities that are being restricted. Any chemical, no matter
           | its controlled status, can be created, possessed, handled,
           | _and consumed_ within the confines of a secure facility --
           | "secure" meaning that the facility takes measures to ensure
           | that the substances won't leave the premises. This is how
           | e.g. MDMA trials are able to continue at some universities,
           | despite MDMA being a controlled substance.)
           | 
           | If you're wondering about making drugs prescription-only: the
           | FDA _does_ determine this, but only kinda. More like, the Act
           | of Congress that defines the FDA into existence, also defines
           | the rules for whether a drug should be prescription-only.
           | Drug companies are aware of the rules, and so they usually
           | just make the drug prescription-only when it should be. The
           | FDA is charged with catching violations, where a drug that
           | _should_ be prescription-only was marketed OTC. (What is the
           | rule itself? It basically boils down to  "if the necessary
           | claims made by the drug are arcane and/or subtle enough, that
           | a non-medically-trained lay-person couldn't reasonably be
           | expected to evaluate their own safety in taking the drug,
           | without a medical professional to act as an interpreter --
           | then lay-people should only be able to access the drug
           | through a scrip from such a qualified medical interpreter."
           | It's still fundamentally about claims and labelling!)
        
         | bequanna wrote:
         | Right, but consider that this is a group of people that is
         | vulnerable and desperate. They are ripe for being taken
         | advantage of.
        
           | pixl97 wrote:
           | Hold up, you're forgetting the whole libertarian model... "My
           | body, my choice, except when you take advantage of me and
           | then I turn the full strength of the taxpayer funded law
           | enforcement apparatus against you"
        
         | Zigurd wrote:
         | No. For the simple reason that there are both legitimate
         | investigative drugs and treatments, and there are quacks and
         | hucksters preying on the desperate.
         | 
         | Your body is not your choice when it gives quacks publicity,
         | never mind revenue, to victimize others and spread
         | disinformation.
         | 
         | There is a lot to be dissatisfied with re conventional pharma
         | and medical practice. But opening the door to cranks is not an
         | improvement. You might be asking "How can you tell which is
         | which?" One of these has publications, has trials planned, etc.
         | The other has the usual signs of quackery.
        
         | nitwit005 wrote:
         | The problem tends to be the giant army of people and businesses
         | that will happily lie to people about medical treatments.
         | 
         | People believe the lies, get ill or die, and the swindlers walk
         | away richer. There's a long, sad history of it.
         | 
         | If you do have a terminal illness though, the government agrees
         | with your premise: https://research.uci.edu/human-research-
         | protections/clinical...
        
         | civilitty wrote:
         | Your body, your cutting edge personal pharmaceutical
         | manufacturing facility - then yes, your choice.
         | 
         | The FDA regulates the manufacturing and distribution of the
         | drugs, not what you put in your body.
        
         | ilc wrote:
         | If you have good information, and your facilities to make a
         | good decision... yes.
         | 
         | Alas, the FDA and friends exist for a reason. Snake Oil, or
         | even things that are downright harmful are out there, that
         | people will sell as cures, or great things.
         | 
         | To strawman: People say all natural is great. I remind them
         | hemlock is all natural, but you probably don't want to digest
         | it.
        
           | ChainOfFools wrote:
           | cancer is all natural too, as are influenza and literally
           | every biological pathogen.
        
           | Spivak wrote:
           | And if the FDA played an advisory role certifying products
           | but not outlawing unapproved goods and informed consent was
           | required for an MD to dispense unapproved drugs I really
           | don't see how we're worse off.
        
         | krick wrote:
         | It should be. It isn't. The usual situation.
        
           | asdfman123 wrote:
           | One complexity is that patients might not be in a good place
           | to evaluate whether a drug is truly viable or it's what they
           | actually want, and they might face pressure from doctors or
           | drug companies.
           | 
           | But I generally agree that it should be the patient's choice.
        
             | Spivak wrote:
             | We already have a process for this called informed consent.
             | 
             | * Medication must be prescribed by and supervised by an MD.
             | 
             | * Doctor has to give you paperwork explaining everything
             | about the drug, that it's not approved and experimental,
             | what the known side effects are _and personally go through
             | it with you allowing you to ask questions._
             | 
             | It's not currently required but you could also mandate a
             | short cooling off period to avoid rash decisions.
             | 
             | In an odd twist of fate the political faction that would
             | love to eliminate the FDA also wants to eliminate informed
             | consent because people are getting medical care they don't
             | approve of. How dare the FDA tell you what you can and
             | can't do with your body -- only we should be allowed to do
             | that lololol
        
             | zhivota wrote:
             | Right, also the state has a vested interest here, because
             | patients bankrupting themselves on snake oil will result in
             | more public money being spent on treatment.
        
         | Jun8 wrote:
         | Very interesting question, touched on famously in The
         | Hitchiker's Guide
         | (https://hitchhikers.fandom.com/wiki/Ameglian_Major_Cow). Some
         | thoughts to consider:
         | 
         | * the person giving consent may not be fully aware of
         | consequence or may not have the faculties to make an informed
         | decision
         | 
         | * even if they are, they may be forced by circumstances, eg. a
         | father selling his kidney for his son's education
         | 
         | * even if the above two are satisfied, the act may be morally
         | deplorable to (parts of) society, eg.
         | https://en.m.wikipedia.org/wiki/The_Ones_Who_Walk_Away_from_...
         | (however, note that society is generally Ok with bodily
         | sacrifice in wars)
        
           | hinkley wrote:
           | The negative consequences of their choices impact all their
           | loved ones or everyone in their social circle.
           | 
           | Also if you work in the hospital you may have to deal with
           | some very disturbing shit if things go badly. People don't
           | just turn into smoke when they die, and anyone who lived
           | through the Pandemic should remember what a horror show a not
           | dead patient can be.
           | 
           | I had a running argument with a friend who was terrible at
           | money management who got very grumpy when anyone addressed
           | the issue of money. It was his choice and none of our
           | business. Except group activities are affected by one party
           | being broke all the time and bringing up money problems.
           | People who care about you are affected by your decisions. You
           | getting defensive about it is all about you, not us. See also
           | our friend with health problems who would stay up late the
           | night before or not eat well/prepare for an event and result
           | in us having to manage them or bail out in the middle. That
           | gets old really fuckin quickly.
        
       | jseliger wrote:
       | In my view, patients should have a "right to try," which is part
       | of fundamental freedom--and this is particularly true for
       | palliative-stage patients without a route to a cure anyway. They
       | are risking essentially nothing.
       | 
       | The FDA is too slow and that's costing lives:
       | https://marginalrevolution.com/marginalrevolution/2021/08/th....
       | The issue is personal for me, too, because I have a squamous cell
       | carcinoma (SCC) recurrence in the tongue, and the treatment that
       | is most likely to cure it is still stuck in clinical trials. In
       | other words, there's a reasonable shot I perish because the FDA
       | is slow, in which case I'll wind up in the "invisible graveyard"
       | that Tabarrok discusses.
        
         | paulpauper wrote:
         | _and the treatment that is most likely to cure it is still
         | stuck in clinical trials._
         | 
         | it seems like you are contradicting yourself. if it's likely to
         | cure, then that would be borne out by the trial? And then it
         | would be rushed for approval. The vast, vast majority of clinal
         | trials for cancer are unsuccessful. A 'successful' drug may add
         | a few months of life vs placebo at a cost of $10k or more per
         | month.
        
           | Mattasher wrote:
           | > if it's likely to cure, then that would be borne out by the
           | trial? And then it would be rushed for approval.
           | 
           | I'm not sure you know how long these things take, even when
           | they work well.
           | 
           | Also, the failure to show a positive clinical effect in a
           | trial mean one doesn't exist, especially at the individual
           | level.
        
         | nitwit005 wrote:
         | > They are risking essentially nothing.
         | 
         | In some cases this is true, but people often want to risk their
         | chance of survival with conventional treatments.
        
         | sam2426679 wrote:
         | What treatment is this? Atezolizumab? (I also have recurrent
         | SCC of the tongue.)
        
           | jseliger wrote:
           | Moderna mRNA-4359:
           | https://clinicaltrials.gov/ct2/show/NCT05533697.
           | 
           | BioNTech has a similar treatment that's also been apparently
           | slow to launch Phase III trials.
        
         | car wrote:
         | Sorry to read about your illness. Without knowing specifics, it
         | is sometimes possible to get access to trial drugs via a
         | compassionate use exemption[0].
         | 
         | You could find out which centers close to you are part of the
         | trial, and contact them about getting access to treatment.
         | 
         | I've previously contacted a drug manufacturers directly to
         | inquire about access via a trial center. This was for a
         | pancreatic cancer drug made by Halozyme. The trial was
         | ultimately halted due to disappointing results.
         | 
         | Please take into account that a drug still in trial may
         | ultimately fail to meet its endpoints, as in the above case.
         | 
         | [0]https://www.fda.gov/news-events/public-health-
         | focus/expanded...
        
         | treeman79 wrote:
         | Went through this for an autoimmune condition with extreme
         | nerve pain. Support forums are full of people that say LDN is a
         | fantastic drug and works wonders. I was on opioids begging
         | doctors to let me try LDN so I could get off the opids. All
         | Refused since they weren't familiar with LDN.
         | 
         | I was finally able to get it online. I no longer take pain
         | medication. Life is basically back to normal.
        
         | jahnu wrote:
         | On this topic here is an excellent examination of it
         | 
         | https://timharford.com/2020/06/cautionary-tales-the-spreadsh...
        
         | taylodl wrote:
         | I understand where you're coming from, but as the parent of
         | someone in the field of pharmaceutical research they have a
         | different view.
         | 
         | First, human beings aren't Guinea pigs. Yes, the FDA is slow -
         | for damn good reasons. We didn't use to do things this way and
         | then we changed it to fix problems. There are reasons things
         | are the way they are and it's very well-understood in the
         | medical field. Medicine is not a move fast and cause pain and
         | suffering kind of field or move fast and kill people kind of
         | field. They're very conservative.
         | 
         | Two, since human beings aren't Guinea pigs when we _do_ do
         | experiments on them with drugs that have been through a very
         | thorough and extensive pipeline already, they 're looking for
         | very specific things. This tends to make a very small
         | population of patients eligible for a trial.
         | 
         | Three, trials are expensive. These aren't drugs that have been
         | scaled-out in production. The costs tend to be exceedingly
         | exorbitant. The medical field is very well aware of the
         | inelastic demand for their services and this opens up new
         | avenues for the unscrupulous to prey on people. Like the used
         | to do in the "good ol' days."
         | 
         | Finally, the fact the treatment you would like to pursue is
         | still "stuck" in clinical trials is indicative they're not
         | convinced of the efficacy of the treatment. I can tell you lots
         | of "promising" treatments never make it out of clinical trials.
         | That's the nature of the beast. Most ideas are dead-ends.
         | 
         | My advice? Don't chase unicorns. Sadly, I've watched too many
         | people in my family die while chasing unicorns and getting
         | obsessed with treatments that are in trial. There are _always_
         | treatments in trial. Live your life and enjoy what time you
         | have to the fullest.
        
           | WalterBright wrote:
           | The counter to this is Sam Pelzmann's "Regulation of
           | Pharmaceutical Innovation" https://www.amazon.com/Regulation-
           | Pharmaceutical-Innovation-...
           | 
           | where he shows, with statistics, that moving fast saves more
           | lives than it costs.
        
           | idopmstuff wrote:
           | > First, human beings aren't Guinea pigs. Yes, the FDA is
           | slow - for damn good reasons. We didn't use to do things this
           | way and then we changed it to fix problems. There are reasons
           | things are the way they are and it's very well-understood in
           | the medical field. Medicine is not a move fast and cause pain
           | and suffering kind of field or move fast and kill people kind
           | of field. They're very conservative.
           | 
           | The problem with this is that they don't appear to be
           | optimizing for the minimization of harm, which seems very
           | obviously to be what they should be optimizing for. Instead,
           | they're optimizing for the minimization of harm caused by new
           | drugs/treatments/etc., while ignoring the harm caused by
           | disease. It's all well and good to not cause suffering
           | through your actions, but suffering caused by inaction (or
           | slow action) is still very much suffering that's caused by
           | your decisions.
        
           | jseliger wrote:
           | My advice to you is that if that's your view, don't take
           | advanced drugs, but get out of my way if I want or need to,
           | and get out of the way of others. You can pursue your path
           | and I will pursue mine.
        
         | msla wrote:
         | Right to try is a cruel scam:
         | 
         | https://sciencebasedmedicine.org/the-cruel-sham-of-right-to-...
         | 
         | > So-called "right-to-try" is a cruel sham that holds out the
         | false hope of survival to terminally ill patients and their
         | families. In return, all they have to give up is patient
         | protections and agree to pay to be guinea pigs to test a drug
         | company's product. The product of an ideology that uses the
         | terminally ill as shields to hide the ideological motives
         | behind the law, which are to hobble the FDA, right-to-try is a
         | terrible idea.
        
           | AbrahamParangi wrote:
           | Wild to say this to someone with everything to gain and
           | little to lose. What is the terrible fate you're protecting
           | terminally ill patients from? Is it worse than death?
        
             | HWR_14 wrote:
             | There are things worse than death. And then there are
             | things that are bad when added to deaths. In the first
             | category might be "scammers who absorb so much cash that
             | they prevent real cures from being researched". In the
             | second might be "people who squander their family's
             | financial future on magic beans in futile attempt to live,
             | but die anyway".
             | 
             | No one would opt into volunteer to be in the second group.
             | But, I can see a lot of, e.g. 50-year-olds, taking a risk
             | thinking they can refill the college-education funds and
             | retirement funds by just working longer than they intended.
             | 
             | I would imagine when dying one of the comforting thoughts
             | is that your estate will continue being able to care for
             | loved ones after you are gone.
        
               | AbrahamParangi wrote:
               | I mean, end of life medical care is already incredibly
               | expensive with very, very little benefit in terms of
               | QALYs saved. We do it anyway. I fail to see how this is
               | different, let people fight to live.
        
               | HWR_14 wrote:
               | No one is arguing people shouldn't be able to fight to
               | live. In fact, the post you are responding to was only
               | talking about if things are "worse than death".
               | 
               | But in general for the larger point, we should make sure
               | that people can fight to live, but that assholes aren't
               | stealing from them by selling magic beans.
        
               | omg_ponies wrote:
               | You're displaying a serious lack of reading
               | comprehension. End of life care provided by palliative
               | specialists is completely different to "scammers who
               | absorb so much cash that they prevent real cures from
               | being researched" and "people who squander their family's
               | financial future on magic beans in futile attempt to
               | live, but die anyway".
        
             | shadowgovt wrote:
             | Historically, the protection was against death and
             | destitution of the family when it was discovered that dad
             | dying of consumption had mortgaged the house to the hilt to
             | afford the overpriced opium.
             | 
             | With the modern social safety net, perhaps the traditional
             | protections can be relaxed.
        
             | juve1996 wrote:
             | > Is it worse than death?
             | 
             | Sure, why couldn't it be? Maybe it has severe, painful side
             | effects. There's a reason many people with stage 4 cancer
             | and low chance of survival decide not to go back on chemo.
             | Maybe it kills them earlier than expected. Then what?
        
             | msla wrote:
             | It's a way for Big Pharma to get cheap research by dangling
             | false hope in front of the desperate.
             | 
             | Of course some here would view that as a positive.
        
         | megaman821 wrote:
         | Since any unproven treatment has a chance to produce immense
         | suffering, you would need to pair this with a right to end your
         | life too. That isn't right that exists in too many places now.
        
         | seanmcdirmid wrote:
         | They had this debate in China recently and the problem was
         | conflict of interest (lots of pricey snake oil for dying
         | patients who can come up with the money). The market has to be
         | regulated even for dying people, if only to prevent scams.
        
           | RobotToaster wrote:
           | Which is why there needs to be a process to approve
           | experimental drugs as at least scientifically plausible.
           | 
           | There's a difference between something that works at least in
           | a petri dish or mice, and something with no plausible
           | mechanism of action like homoeopathy.
        
           | akira2501 wrote:
           | That seems like a claims and marketing issue, which is
           | entirely separate from merely producing a drug and selling it
           | when asked. I think it's fine that the FDA regulates
           | advertising, I don't think it's fine that they act as
           | gatekeepers to pharmaceutical products.
        
             | sacrosancty wrote:
             | [dead]
        
           | AlexAndScripts wrote:
           | Perhaps you can just restrict it to companies with a history
           | of bringing drugs to market with FDA approval? A little
           | regulatory-capture, but probably worth it for the greater
           | good.
        
           | varelse wrote:
           | [dead]
        
           | mitthrowaway2 wrote:
           | Perhaps the patients should be allowed to use experimental
           | treatments only under the condition that it is offered for
           | free; the upside for the company is that if it works, they
           | get the evidence of efficacy.
        
             | rafark wrote:
             | This should be the solution. If they're trials for an
             | unproven solution, why should they pay anything at all. I'm
             | any case, it should be the other way around; it's the
             | companies who should pay the person for subjecting them to
             | something very likely to be dangerous and painful.
             | 
             | In any case, I agree with the sentiment here. People should
             | have the right to choose.
        
             | ramraj07 wrote:
             | This is how it already works - this is what a clinical
             | trial is. If you want to include the data point of a
             | medicine working well as admissible, then you better have
             | more than one patient try it at a time. Unless of course
             | your drug is so good at curing patients who are absolutely
             | terminal (like ibrutinib was). But most meds are not that
             | much of a blockbuster. Thus you don't know if a single
             | patient survived if it's because this medicine was very
             | effective or if it was just as good as any other available
             | treatment regimen.
        
               | iskander wrote:
               | >This is how it already works - this is what a clinical
               | trial is.
               | 
               | That's not at all how clinical trials work. If and when
               | someone decides to advance a drug to the next stage of
               | development, it's done because they think there's a
               | sufficiently profitable market at the end of the road. So
               | lots of extremely promising drugs stall out if the
               | numbers don't make sense. Furthermore, the trial
               | enrollment process itself is cumbersome and often your
               | only entrypoint is email "trials@pharmacompany.com" and
               | hope you can a response and can navigate their arbitrary
               | screening process. Speaking of screening: trials are full
               | of exclusion criteria. They can get copy-pasted between
               | trial protocols and often have no real reason excluding
               | you. What's the washout period for your last line of
               | chemo? Ever had any kind of immunotherapy? &c &c From the
               | point of view of whoever is trying to get a drug approved
               | it's better to be safe than sorry wrt any kind of
               | uncertainty in a patient's medical status or treatment
               | history. But that means that there might be a drug that
               | looks extremely promising from previous trials but the
               | only current trial excludes you for a small reason.
        
               | ryanwaggoner wrote:
               | I assume they meant that clinical trials are already free
               | for the patient, as suggested by the comment they were
               | responding to.
        
               | Freebytes wrote:
               | The problem with clinical trials is that they are looking
               | for specific patients, though. And they will exclude
               | patients that introduce confounding variables. Some
               | studies exclude patients that are closest to death
               | because they will interfere with the trial as well.
        
             | Wowfunhappy wrote:
             | > the upside for the company is that if it works, they get
             | the evidence of efficacy.
             | 
             | They don't, though. They need a control group.
        
               | farseer wrote:
               | They can then apply to launch formal clinical trials with
               | a control group. This initial evidence of efficacy is of-
               | course anecdotal evidence with more traceability.
        
               | threatofrain wrote:
               | I think it's common practice to give life saving
               | treatment to the control group after there is some
               | measure of confidence that the drug works.
        
               | seanmcdirmid wrote:
               | They don't exactly need a control group if the chance of
               | living N weeks is effectively zero. They would need it
               | for something like living N weeks and living N+1 weeks,
               | but any kind of change from an individual expected
               | outcome would be useful signal for maybe more rigorous
               | testing.
        
               | caeril wrote:
               | There is a standard of evidence above guesswork and below
               | controlled trials, that is still useful: you accumulate
               | enough survival rate data of whatever specific terminal
               | condition you're hoping to treat, and compare it to the
               | baseline untreated survival rate, which is already known.
               | 
               | Any statistically significant difference there can then
               | incentivize a drug research company to invest in the
               | (expensive) clinical controlled trial process.
               | 
               | It's strange that people here are actually saying it's
               | better to waste perfectly good research opportunities and
               | watch patients die, than to risk having anything less
               | than perfect evidence of efficacy.
        
               | mitthrowaway2 wrote:
               | The people who have already died to-date of your terminal
               | illness aren't a good enough control group to tell that
               | your cure works? This is the absurdity of frequentist
               | statistics. If you can't tell the difference between
               | recovering from the treatment and recovering by natural
               | luck, then either the treatment is barely effective at
               | all, or the doctor had no basis to tell you in the first
               | place that you had a terminal illness.
        
               | jostmey wrote:
               | That is correct, the people that have already died are
               | unable to act as effective controls. To establish the
               | medicine causes the disease to go away, you have to use
               | something like a randomized trial. Otherwise, causation
               | is not established. It's a very difficult problem and a
               | lot of smart people have try to come up with better
               | systems.
        
               | mitthrowaway2 wrote:
               | With all due respect, why? This seems fallaciously wrong.
               | 
               | It is rather akin to saying that I can't tell whether
               | seatbelts reduce car-crash fatalities simply by comparing
               | collision fatalities from 1967 seatbelt-lacking car
               | models with otherwise-identical 1968 seatbelt-equipped
               | models; I would need to actually randomly and secretly
               | sabotage a certain percentage of the seatbelts from
               | 1968-model cars, while deliberately ignoring everything I
               | know about prior fatality statistics. Even if every
               | automobile collision without seatbelts was fatal, and
               | every collision after seatbelts became mandatory was
               | survived, even if nothing about the cars or driving
               | conditions had changed, you're implying that it wouldn't
               | provide any evidence of the efficacy of seatbelts, unless
               | we conducted a new trial from scratch with a randomized
               | control group as though we had no prior data?
               | 
               | What is the actual difference, in terms of causal
               | evidence, between someone who died of the same disease
               | before the study officially begins, and someone in the
               | "control group" who dies after the study begins?
        
               | shadowgovt wrote:
               | Almost nothing about medicine operates nearly as cleanly
               | as that example; that's one of the major challenges with
               | medical science. The seatbelt analogy breaks down in this
               | context because the hypothetical of "Even if every
               | automobile collision without seatbelts was fatal, and
               | every collision after seatbelts became mandatory was
               | survived, even if nothing about the cars or driving
               | conditions had changed" doesn't reflect medical reality
               | (and in the rare instances where it does, i.e. when
               | improvement for the test group becomes obvious,
               | immediate, and apparently side-effect free, it _can_
               | become morally imperative to discontinue the control
               | group).
               | 
               | In medicine, you get confounding factors like change in
               | standard of care year-to-year and facility-to-facility.
               | You almost never get the kind of "clean-room" trials you
               | get in mechanical engineering (and, indeed, the processes
               | to create them would often themselves be unethical). So
               | the best you usually get is trying to reason around (to
               | torture the analogy a bit) "Well we introduced seatbelts
               | three years ago and relative to the year prior to that,
               | fatalities went way down... Oh wait, but COVID also
               | happened the same year we introduced seatbelts and
               | everyone stopped driving" if you compare a current trial
               | to past non-trial standard care as the control group.
        
               | mitthrowaway2 wrote:
               | Isn't this just the standard challenge of separation of
               | signal and noise that exists in all disciplines, though?
               | It seems that it would be better dealt with by general
               | Bayesian methods than by strict adherence to a
               | controlled-trial process that requires ignoring or even
               | _discarding_ large quantities of data (including every
               | patient who ever had the disease prior to the start of
               | the trial, which for rare diseases, might even be the
               | _majority_ of the data!)
        
               | shadowgovt wrote:
               | > It seems that it would be better dealt with by general
               | Bayesian methods than by strict adherence to a
               | controlled-trial process that requires ignoring or even
               | discarding large quantities of data
               | 
               | What is the Bayesian prior on "After receiving the COVID
               | vaccination, patient died when they were struck by
               | lightning?"
               | 
               | This is what I mean when I say the 'clean room' practices
               | that are standard for most other fields of science would
               | be considered unethical for medical trials. You can't,
               | generally, lock people in a box for months to eliminate
               | other confounding factors when trialing medicine; the
               | best approach we have, therefore, is to minimize
               | confounding factors by minimizing variables in space,
               | time, &c. Yes, if we could lab-rat humans, keep them in
               | controlled environments perpetually, we could use the
               | previous in-a-box state as a comparison to the current
               | state, _probably._ That 's obviously a non-starter.
               | 
               | (There are some categories of medical research where
               | time-variance has been used; it's just not generally an
               | acceptable signal source, IIUC, for drug and therapy
               | trials. If for no other reason than not nearly enough
               | information has been captured about unrelated past
               | patients to be compared to a current trial because
               | relevant information to monitor was not known when
               | monitoring past patients).
        
               | mitthrowaway2 wrote:
               | > What is the Bayesian prior on "After receiving the
               | COVID vaccination, patient died when they were struck by
               | lightning?"
               | 
               | Mathematically not difficult to deal with, which is why
               | you intuitively know the answer already, because it's
               | approximately the same way your brain works naturally.
               | The chance of dying when you are struck by lightning is
               | about 10%,[1] which completely overwhelms the chance of
               | the vaccine coincidentally killing you at the same moment
               | by several orders of magnitude; while you could use the
               | this datapoint if you want, Bayesian analysis will still
               | confirm that it has approximately zero evidence
               | supporting (or refuting) that the vaccine causes death,
               | so Bayes' theorem effectively drops that patient out of
               | the analysis. Which is the same thing you'd probably have
               | done intuitively, unless some kind of formal controlled-
               | test study rule prevented you from doing what would
               | normally be the correct procedure. (Or worse, forced you
               | to subject an unvaccinated control-group patient to a
               | lightning strike, just to maintain control...?)
               | 
               | But, since your patient died from the lightning strike
               | rather than surviving it, there is a small signal present
               | that points towards "the vaccine increased the chance of
               | the lightning strike being fatal", which is a postulate
               | that deserves a high initial skepticism until someone can
               | propose a mechanism. But if you notice that multiple
               | people die from lightning strikes after getting
               | vaccinated, such that their lightning-strike survival
               | rate is below the unvaccinated population's, you can
               | start to update on that, and if it keeps happening, it
               | becomes worth your time to investigate a potential
               | mechanistic explanation. Like, the vaccination causing
               | people to be less sweaty somehow.
               | 
               | [1] https://www.britannica.com/one-good-fact/what-are-
               | the-odds-o...
        
               | shadowgovt wrote:
               | ... or the unvaccinated population tends to cluster, for
               | sociopolitical reasons, in a region of the country, where
               | lightning strikes are unusually powerful. IRL confounding
               | factors abound.
               | 
               | Sweatiness is a good example of the sort of thing that
               | would be hard to determine by comparing to past sample
               | groups, since it's a rarely recorded piece of data.
        
               | nick__m wrote:
               | If a disease at a certain well defined stage has a 100%
               | fatality rate after 6 months, why would you need a double
               | blind trial if some patients are still alive 1 year after
               | taking your drug ?
               | 
               | The causality is pretty clear and while you might not
               | claim that it double the life expectancy it would IMHO be
               | immoral not to fast track the approval of that drug.
        
               | Zak wrote:
               | People who already died are _less_ effective controls
               | than double-blind controls getting a placebo, but they
               | 're not _ineffective_.
               | 
               | Given a treatment with a large effect size like
               | penicillin, a causal link will be very easy to establish
               | even with a suboptimal control group.
        
               | [deleted]
        
               | londons_explore wrote:
               | And that is why you shouldn't be able to ask for the
               | experimental treatment... You should be able to ask to be
               | part of a trial of the experimental treatment.
               | 
               | Remember that if 10 treatments are being tried at once,
               | you can divide the pool of participants so that only a
               | smallish percentage are part of the control group.
        
               | zo1 wrote:
               | I have no better words: that is evil.
        
               | [deleted]
        
               | shadowgovt wrote:
               | Can you clarify why that is evil? Are you referring to
               | the use of control groups or the division of the test
               | group into several overlapping trial compounds?
        
               | captaincrisp wrote:
               | I bet it's control groups.
               | 
               | The FDA thinks similarly. In late 2021, they canceled
               | trials of Paxlovid because it was immoral to have a
               | control group. They did not then _waive the trial
               | requirement_, meaning Paxlovid was both too proven to
               | deny but too unproven to be administered.
        
               | Wowfunhappy wrote:
               | ...I think that's basically how it works? If the company
               | is running a trial, you can enroll in the trial. AFAIK
               | being in a trial is free for participants.
               | 
               | Of course, there are any number of reasons someone may be
               | rejected from the trial. If that happens, the company
               | isn't going to just freely give them the drug anyway,
               | because it wouldn't provide scientifically valid data.
               | Also, no one would enroll in a trial (which carries the
               | potential of getting the placebo) if they could get the
               | treatment outside the trial.
        
               | starkparker wrote:
               | The drug itself might be paid for, as well as tests under
               | the scope of the study (which might be narrow), but
               | services to administer the drug, and tests or treatment
               | for effects not in the scope of the study, aren't always
               | covered. Or, in the stupidest cases, approval gets bogged
               | down by the drug company, patient, or administering
               | clinic/practitioner trying to get the patient's insurance
               | to cover whatever's not covered by the trial for so long
               | that the patient no longer qualifies (or is dead) by the
               | time insurance relents and agrees to pay.
        
               | torstenvl wrote:
               | > _They don 't [get evidence of efficacy], though. They
               | need a control group._
               | 
               | This is false. Control groups, preferably in double-blind
               | studies, are an essential part of best practices.
               | However, the bar for what constitutes _evidence_ is much
               | lower than that.
               | 
               | Evidence is any fact that makes a relevant conclusion
               | more or less likely. Evidence need not be conclusive in
               | and of itself. Over time, the cumulative effects of less-
               | strong evidence can form the basis for a reasonable
               | inductive conclusion. Sorry to be trite, but as an
               | example, a person can have evidence that their romantic
               | partner loves them without the use of an identical twin.
               | 
               | Insisting on gold standard medical evidence before
               | _allowing_ someone to undergo life-saving treatment--when
               | the preponderance of the evidence that does exist
               | supports that treatment--is, to be blunt, the very
               | definition of depraved heart murder. It demonstrates a
               | wanton disregard toward human life in the face of the
               | known likelihood that it will result in some number of
               | deaths.
               | 
               | More broadly, however, it is an extremely poor policy, in
               | that this meme both weakens society's critical thinking
               | generally and--among those who see through the elitist
               | charade--significantly weakens the respect of those
               | scientists who make the claim.
        
               | A_D_E_P_T wrote:
               | > Control groups, preferably in double-blind studies, are
               | an essential part of best practices.
               | 
               | I wouldn't go that far. I think that a paradigm built
               | upon a broader evidence base -- e.g. with far more
               | extensive postmarketing surveillance of drugs -- would be
               | more ethical, of more benefit to society, and ultimately
               | more effective.
               | 
               | Double-blinded studies can miss, can be confounded by
               | placebo effects, can easily be confounded by crooked
               | researchers, and are frequently just plain unethical from
               | first principles. I don't think that they should be
               | considered "essential."
        
               | random78965 wrote:
               | I think all your criticisms of randomized controlled
               | trials (apart from the ethical one) apply to your
               | suggested approach, no?
               | 
               | RCTs are the gold standard for demonstrating efficacy
               | precisely because of the controls. I agree that they're
               | not going to give you enough info about potential side-
               | effects - a thorough monitoring program is definitely
               | necessary for that.
               | 
               | But without RCTs, showing that a drug works would be much
               | harder. How would you weed out the snake oil?
        
               | [deleted]
        
               | TylerE wrote:
               | Not always. In some cases, like rabies, the control group
               | is 100% rate of death.
        
             | londons_explore wrote:
             | This sounds like the best way to do it.
             | 
             | The company would still need a blinded control group to be
             | able to demonstrate the effectiveness of any treatment.
             | 
             | However patients should be allowed to enroll for free into
             | multiple treatment trials at the same time. For a given
             | number of people and treatments, enrolling in multiple
             | trials simultaneously gives more science output, _and_ more
             | chance of success for the participants, if you assume that
             | ineffective treatments rarely are very harmful.
        
               | hutzlibu wrote:
               | "However patients should be allowed to enroll for free
               | into multiple treatment trials at the same time."
               | 
               | But this would likely mess up any data, you can get. How
               | can you tie the cure or the bad sideeffects to any drug
               | then?
               | 
               | Apart from that, sure, I think patients should have the
               | right to try anything.
        
               | londons_explore wrote:
               | Bad side effects caused by participating in other trials
               | would happen with equal frequencies in the control group.
        
               | mitthrowaway2 wrote:
               | You just end up with a matrix of treatments. Whatever
               | results you observe from someone undergoing treatments X
               | & Y goes in the "X&Y" box, not the X box and the Y box.
        
             | civilitty wrote:
             | That would be the bare minimum in practice. That's already
             | the case: without premarketing approval (clinical trials),
             | companies are not allowed to charge anything for medicine
             | or medical devices. They're not even legally allowed to
             | ship them interstate until the premarketing application is
             | accepted.
        
           | citizenpaul wrote:
           | I was going to make this point. People at EOL by default
           | often have estates, investments, retirement accounts. In
           | other words huge chunks of money/wealth that unscrupulous
           | people may wish to get their hands on. Combine that with the
           | desperation of a dying person and you have the perfect
           | condition to create a very profitable scammer market for
           | worthless treatments.
           | 
           | This also harms eveyone because all the money pouring into a
           | treatment that was a scam from day one is oppertunitu y lost.
        
             | throwuwu wrote:
             | I think the argument is to loosen the regulation on human
             | trials, not to drop all regulation on drug companies. They
             | should still have to prove that they're doing legitimate
             | research and have had some success before opening it up to
             | humans who are terminally ill. They should still be legally
             | culpable for negligence and fraud.
        
               | TeMPOraL wrote:
               | Keep in mind that it's not the pharma companies that are
               | the only, or even most notorious, scammers that would
               | benefit. _Families_ of the dying one are a major risk
               | factor. The difficult[0] truth is, plenty of families
               | would accelerate the demise of a terminally ill or
               | elderly[1] if it were possible. Like with euthanasia, any
               | elective experimental treatment that carries increased
               | risk of death, could become something the patients get
               | pressured or manipulated into by their families.
               | 
               | --
               | 
               | [0] - The situations can be ethically and emotionally
               | complex, so I'm not passing any generalized judgement,
               | other that this is something a person might be concerned
               | about when contemplating the possibility of ending up in
               | this situation in the future.
               | 
               | [1] - Arguably the same thing, but that's another topic.
        
             | ChainOfFools wrote:
             | As a general principle, any set of circumstances which
             | results in net increased influence of people who are
             | demonstrably amoral with regard to the public welfare,
             | should have as many barriers as possible put up to obstruct
             | the success of such people.
             | 
             | Bad money chases out good, increasing the fraction of money
             | in bad hands by billions or tens of billions is going to
             | have a palpable effect on the stability of the world.
        
             | civilitty wrote:
             | _> This also harms eveyone because all the money pouring
             | into a treatment that was a scam from day one is
             | oppertunitu y lost._
             | 
             | You guys remember Theranos? When Safeway announced their
             | deal with Theranos in 2012, a bunch of companies working in
             | blood diagnostics folded because they couldn't raise money
             | or because their investors clawed back entire rounds.
             | 
             | A couple of friends had just raised a series B round to
             | commercialize their surface plasmon resonance blood testing
             | device, which would have _actually done what Theranos
             | promised_ with onsite blood testing (except with proper
             | blood draw, not a finger prick). They were getting the
             | product ready for golden standard testing with a CRO when
             | investors decided it wasn't worth trying to compete with a
             | Theranos already in the pocket of major pharmacies and
             | pulled the series B funding.
             | 
             | Patents ended up getting sold to some patent troll shortly
             | before the news broke that Theranos was a scam.
             | 
             | The people who funded Theranos weren't even desperate, just
             | greedy. Imagine what fingers they'll put on the scales when
             | they're actually staring death right in the face? It'll be
             | a disaster.
        
           | rajanaccros wrote:
           | I guess it would depend on the reason for denial to a
           | patient. If it is solely because it isn't regulatory approved
           | _yet_ then that doesn 't seem sufficient. If the drug was
           | provided for free from the pharma company it would be a
           | faster path to a human trial which would be a win/win for all
           | involved with the only possible negative for a person who
           | doesn't have anything to lose.
        
           | short_throw wrote:
           | There are tradeoffs here, but the current approach seems to
           | protect people's inheritances better than people's lives.
           | 
           | Selling straight up snake oil is still fraud, and letting
           | money be thrown at overhyped but ineffective treatments is a
           | smaller tragedy than forcing people to die when treatments
           | exist.
        
           | nohuck13 wrote:
           | If they can come up with the money then who cares?
           | 
           | It would be a much better case for regulating if there were
           | some external payer.
        
             | seanmcdirmid wrote:
             | Their parents and/or kids come up with money. It is
             | basically theft. If you are ok with theft, fine, otherwise
             | we shouldn't exempt it just because of the false hope it
             | provides.
        
           | jccalhoun wrote:
           | Ahhh. This answers a question I've had: I'm in the USA and
           | one of my senators has been banging the drum for allowing
           | patients access to experimental drugs for a few years. I have
           | wondered why this was an issue for him. Maybe I'm cynical but
           | this and easy PR win for him seems like good reasons why.
        
           | warent wrote:
           | Did the Chinese government ultimately regulate the market to
           | protect people and prevent this kind of corruption?
        
             | DiscourseFan wrote:
             | The regulation is approval by a governmental agency through
             | clinical trials
        
             | dspillett wrote:
             | IIRC it did, though the cynic in me would suggest that by
             | "this kind of corruption" what it prevents is the kind of
             | corruption that government officials don't benefit from.
             | 
             | I trust the Chinese government less than I trust my own
             | with regard to doing the right thing (just because it is
             | the right thing or indeed at all), and that is a pretty low
             | bar...
        
             | seanmcdirmid wrote:
             | This wiki article is probably the best place to start:
             | 
             | https://en.m.wikipedia.org/wiki/Death_of_Wei_Zexi
             | 
             | Then there was some movement on the issue in 2019:
             | 
             | https://www.bloomberg.com/news/features/2019-12-10/cancer-
             | tr...
             | 
             | I'm not sure where they ended up due to COVID happening
             | next.
        
           | aeternum wrote:
           | This is a very weak excuse. If preventing scams is the main
           | concern then old people should also be banned from purchasing
           | real estate, timeshares, large donations, perhaps even
           | giftcards in certain quantities.
           | 
           | You can't have freedom without some chance of people making
           | bad choices.
        
             | seanmcdirmid wrote:
             | Dad asks me for a lot of money to help him buy a time
             | share, I'll feel ok saying no.
             | 
             | Dad asks me for a lot of money for a snake oil cure that
             | might prevent him from dying from bile duct cancer in a
             | month or two...how am I going to say no to that?
        
         | Veserv wrote:
         | The link you posted has a addendum which links to this:
         | https://astralcodexten.substack.com/p/details-of-the-infant-...
         | 
         | In the more well researched followup by the same person, the
         | author of Astral Codex, we see that the FDA did not block or
         | slow the approval. It was that the manufacturer had no interest
         | in even submitting a application. In fact, the FDA regularly
         | granted usage exemptions, granted a broad exemption for
         | research, and even directly funded one of the first trials even
         | though they are not primarily a funding body.
         | 
         | The actual moral of the story maybe is that we should let third
         | partys submit applications? It seems like there would be little
         | risk of bad outcomes as they still need to do the approval
         | process. It aligns incentives better as the people ultimately
         | at risk can deploy resources comparable to their QoL
         | improvement instead of the expected increased sales volume at
         | current prices. There is a obvious problem that the production
         | process is inextricably linked to the final output so a non-
         | manufacturer has limited control and insight into a core
         | component that introduces the possibility of regression, but it
         | seems relatively doable to develop protocols for handling that
         | if they do not already exist.
         | 
         | edit: To be fair, once the application was submitted it still
         | took 6 years for approval. There are likely large procedural
         | costs in doing the exemptions and testing that make inaction
         | preferable. So, in some sense exemptions and lacking interest
         | in approval may be problems of their own creation, but on net
         | the overall outcome seems fairly reasonable. Actual
         | improvements in procedural matters are likely too nuanced for a
         | random layperson like myself to comment on.
        
           | civilitty wrote:
           | _> The actual moral of the story maybe is that we should let
           | third partys submit applications?_
           | 
           | The application isn't a single page form, it's hundreds to
           | thousands of pages detailing everything about the clinical
           | trials ranging from the success criteria for each phase, the
           | doctors and hospitals involved in the trials, and even tiny
           | details like how much blood is going to be drawn, when it
           | will be drawn, and how it's going to be tested.
           | 
           | They're impossible to write without the participation of
           | almost everyone involved in the process since a significant
           | part of premarketing approval is quality control of the final
           | drug manufacturing process.
        
             | Veserv wrote:
             | Yes? I meant they should be allowed to run independent
             | clinical trials and then submit for approval.
             | 
             | I also did point out that the integral nature of the
             | manufacturing process is a obvious potential problem. It,
             | however, does not seem like a insurmountable problem. The
             | specifications on sourced components and the quality
             | control processes applied to them is already integral to
             | the drug manufacturing process. This would just move it one
             | level further up where the final drug produced by some
             | existing production process is a "component". They also
             | already approve drugs for different uses and evaluate
             | existing drugs for new uses, so it does not seem that
             | qualitatively different from some existing approval
             | procedures. I am not sure of the exact details and am not
             | proposing a specific solution, but it certainly does not
             | seem to be a deal breaker.
        
               | [deleted]
        
             | Faaak wrote:
             | Not at all in the field, but are there standardized
             | clinical trial "frameworks" that can be used in order to
             | simplify the process ?
        
               | civilitty wrote:
               | Designing clinical trials from scratch is a very
               | difficult and time consuming process so almost all of
               | them are modeled after previous successful trials
               | targeting the same class of medicine - as specific to the
               | new drug as possible.
               | 
               | There's a lot of copy pasting followed by customization -
               | often by "contract research organization" consultants who
               | specialize in different types of clinical trials - but
               | there are no "frameworks" as we would understand it in
               | software engineering.
        
         | BrandoElFollito wrote:
         | I think that patients should be able to choose, but in reality
         | the advantage will be for them only.
         | 
         | Due to the lack of control groups them taking the pill does not
         | make the science go _forward_ (in the sense that it is an
         | indication for the use).
         | 
         | I believe however that they're is a great interest in the
         | _stopping_ effect: the evidence that the treatment is
         | ultimately harmful.
         | 
         | Still, this is a win-win:
         | 
         | - if the patient gets better, good for them. Does not help the
         | pharma company.
         | 
         | - if the patient gets collateral negative effects, too bad for
         | them (but they were very bad anyway). This helps the pharma
         | company.
         | 
         | Coupled with euthanasia, this would be a humanitarian solution
         | for the extremely sick.
        
           | RealityVoid wrote:
           | I'm a bit puzzled why you couldn't extract useful information
           | even _without_ a control group. Let's say we have a disease
           | that we know that kills you. If you take the treatment and
           | you don't die, we have pretty damn' positive evidence it
           | works. The control group is the... You know... Many other
           | people that don't take the medicine and die.
        
             | BrandoElFollito wrote:
             | This is probably a good indication, but you do not know if
             | it is the pill that is making the effect. It may also be
             | the placebo effect.
             | 
             | It may also be that on day 6 you get better (no matter of
             | you took the pill or not), and then worse on day 20, but
             | much worse than without the pill.
             | 
             | Still, this is a statistical wink so to speak (paraphrasing
             | xkcd (https://xkcd.com/552/)).
             | 
             | To be clear: I am all for patients experimenting on
             | themselves when they do not have much to lose (and whenever
             | they please, but they have to take their responsibilities
             | then). Plus euthanasia if the experiment goes south.
        
         | [deleted]
        
         | HWR_14 wrote:
         | Patients who are near the palliative-stage can try many drugs
         | in the FDA approval process. The doctor has to get
         | "permission", but that is granted over 99% of the time. IIRC,
         | it mostly involves making sure the doctor has read up on the
         | research, believes it is necessary to save the patient's life,
         | and agrees to report back on the treatment to the FDA.
         | 
         | If there really is a treatment that is significantly better
         | than current treatments, have your doctors talked to you about
         | this? It was codified into law about a decade ago, but that's
         | not so new that they shouldn't be aware of the program.
        
       | paxys wrote:
       | Lipitor was formulated in 1985, went through an expensive and
       | exhaustive trials process which concluded in 1994, and hit the
       | market in 1996. Today it is one of the best selling drugs in the
       | world, has revolutionized heart health, and saves tens of
       | thousands of lives in the US annually.
       | 
       | So was Lipitor's development and approval process a failure? If
       | you ask some patients and their families who were stuck in the
       | early 90s with hope but no access to the drug, they would
       | probably say so. And I understand the emotions involved, but the
       | truth is that if human civilization has existed without a
       | lifesaving treatment for hundreds of thousands of years, delaying
       | it for a couple more to better under its effectiveness is the
       | right decision for the public good.
        
         | chiefalchemist wrote:
         | Yes, that's a great example of a success story. However, other
         | drugs have gone through the same process and were eventually
         | found to not be as effective as during the trial; or worse,
         | they were found to be dangerous.
         | 
         | Aside from the threat to the patients, there's the opportunity
         | cost of such "misfires."
         | 
         | In the US, we can upon death donate our organs to others in
         | need. We can also, again upon death, donate our bodies to
         | science. Yet while alive, we can't decide to help ourselves,
         | and ideally others as well? That doesn't make sense.
        
         | xxpor wrote:
         | >dthe truth is that if human civilization has existed without a
         | lifesaving treatment for hundreds of thousands of years,
         | delaying it for a couple more to better under its effectiveness
         | is the right decision for the public good.
         | 
         | I don't understand how that's the counterfactual though. Let's
         | say the patents we're talking about are ones that in the early
         | 90s had a 90%+ chance of dying without Lipitor. Not giving them
         | the drug simply to have a control group is just as morally
         | fraught as giving people completely untested drugs that kills
         | them. To suggest otherwise is just status quo bias.
         | 
         | It's clearly a complex issue where you draw the line, but we
         | should be able to have an intelligent conversation as a society
         | about probabilities and tradeoffs.
        
           | paxys wrote:
           | People who don't get a drug while it is under development
           | aren't in a control group. People in a _clinical trial_ who
           | don't get the drug are in the control group. Yes it is a
           | morally tricky situation, but the people who signed up are
           | aware of it. Everyone else simply doesn't get the drug
           | because the drug hasn't been approved yet.
        
             | AbrahamParangi wrote:
             | The point that people are making is that it's the trolley
             | problem. Yes you actively kill one person by making a drug
             | available prematurely but you kill 5 people through
             | inaction otherwise.
        
               | paxys wrote:
               | More like - you kill 5 people through inaction or kill
               | tens of thousands because the drug wasn't able to be
               | studied correctly before release.
        
               | AbrahamParangi wrote:
               | You claim a specific belief here about the odds ratios,
               | but hypothetically if the odds ratio were more similar to
               | what I claimed than what you claimed, would you change
               | your opinion?
        
               | juve1996 wrote:
               | It's not the trolley problem because in the trolley
               | problem both outcomes are clear to the decider.
        
       | Am4TIfIsER0ppos wrote:
       | If it will make them better there is no problem. If it won't make
       | them better it might be a scam. If it will make them worse just
       | call it euthanasia.
        
       | angry_moose wrote:
       | I'm in medical and one major issue with Compassionate Use
       | programs [1] is there often just isn't the supply yet to divert
       | doses/devices to non-trial patients. By definition they are pre-
       | release treatments, which means manufacturing is still ramping up
       | and is often only available in small quantities.
       | 
       | We would love to be able to provide access to our device to
       | everyone (its quite promising), but we are barely able to meet
       | demand for the clinical trial.
       | 
       | With those restrictions, the call was made that we had to end
       | compassionate use treatments for the foreseeable future - with
       | limited supply they had to be devoted solely to the clinical
       | trial, which is designed to give the maximum possible data about
       | efficacy, not just anyone it might help.
       | 
       | 1) https://www.fda.gov/news-events/public-health-
       | focus/expanded... - The FDA is actually pretty good about
       | allowing these treatments
        
         | hinkley wrote:
         | Sounds a lot like Mythical Man Month territory as well. More
         | patients means more techs and more doctors to offer advice/test
         | for side effects, and you can't just wave a wand and get those.
         | You have to invest in people to roll out a product.
        
           | civilitty wrote:
           | Exactly. Patient selection in clinical trials is already
           | _notoriously_ difficult even with phase I trials where it 's
           | a few dozen healthy people at most. Finding the right
           | patients so your control and test groups don't have a lot of
           | confounding factors is a field unto itself. Doing so with
           | terminal patients, who often have a lot of things going on
           | including just the psychology of dying, is even more so.
           | 
           | Almost everyone hires out to contract research organizations
           | that have entire departments dedicated to the process with
           | years long relationships with major hospitals and patient
           | groups that serve as "sales funnels" for their clinical
           | trials.
        
       | hobotime wrote:
       | My dad willingly tried an experimental drug. It killed him, but
       | he would have died a week or two later. We now know that the drug
       | doesn't work as well as we all would like.
       | 
       | His death was valuable, and moved our scientific knowledge
       | forward.
        
         | VirusNewbie wrote:
         | Sorry to hear. I do agree, that was a noble death. Respect to
         | your father for the choice he made.
        
       | Glench wrote:
       | I'd also love to see psychedelic-assisted therapy approved for
       | therapeutic use in dying patients. The outcome studies for
       | exactly this scenario have been really good from my
       | understanding.
        
       | Simulacra wrote:
       | Right to try should be absolutely fundamental. If patients want
       | to try unproven drugs, give it to them, it's their body, their
       | lives. Especially if they're terminal. I see absolutely no
       | downside. The government really has no business telling us how to
       | manage our healthcare, but dammit they try!
        
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