[HN Gopher] Developing a cancer drug without Big Pharma: this ho...
___________________________________________________________________
Developing a cancer drug without Big Pharma: this hospital shows it
can be done
Author : yread
Score : 175 points
Date : 2024-11-27 21:35 UTC (1 days ago)
(HTM) web link (www.ftm.nl)
(TXT) w3m dump (www.ftm.nl)
| JSR_FDED wrote:
| Translated, unpaywalled:
|
| https://www-ftm-nl.translate.goog/artikelen/ruzie-tussen-zie...
| ALittleLight wrote:
| That's interesting. I was just reading about how high dose IV
| vitamin c can induce cell death in a wide variety of cancers, but
| somehow, despite this being known for decades, nobody has done
| rigorous research on it.
|
| https://www.cancer.gov/research/key-initiatives/ras/news-eve...
|
| From what I can tell there are several things like this - that
| have promising anti cancer effects, that just don't really get
| that much attention because there's not a patent possible.
|
| Really makes me think much less of medical science. Even if you
| couldn't patent any thing you'd think you could get fame and
| fortune by devising a useful therapy.
| ben_w wrote:
| IIRC medical research is _really expensive_ , hence money-
| seeking is to fund it within capitalism.
|
| Also IIRC the rewards are oversized compared to the costs, but
| that doesn't change that the costs are also huge. Does mean I'm
| generally in favour of getting every government to quadruple
| public spending on this though. Whatever the current spend is,
| we can do more.
| ALittleLight wrote:
| I don't see how something like high dose vitamin C IV is very
| expensive. I would assume a handful of oncologists could do
| the whole thing themselves. We get X patients a year, we
| randomly suggest the vitamin C IV to half, the half with
| vitamin C did better or worse by these metrics. Vitamin C is
| not expensive and they have to collect the outcome data for
| everyone involved anyway - so where is the expense coming
| from?
|
| If it has benefits then more doctors will start to do it and
| more data will become available. If not, onto the next thing.
| ericmay wrote:
| I'm not a physician and not in the medical field, but I
| would hazard a guess that a lot of the expense comes from
| just doing the work. What specific doctor will administer
| the vitamin C and monitor the patients? How do you isolate
| that the vitamin C dosage increase is effective? Who is
| going to create the vitamin C in the proper dosages? Who is
| going to write about it to make sure that it's legally
| approved? The human body is very sophisticated. The trials
| have to be done in a scientific way, following the
| established procedures of ethical medical treatment, peer
| reviewed, etc. And let's say you start giving vitamin C to
| some of these patients and they start having bad reactions
| and it makes their disease worse? Who covers the hospital
| stay? Who pays for their care?
|
| Just looking at a few things there I'm guessing that's a
| few million dollars _at the very least_.. and even so you
| have to look at opportunity cost. Is this the best and most
| promising path of research for the physicians and
| researchers? Are there more promising compounds? Etc.
| cen4 wrote:
| It happens already. You just have to find the docs who do
| it. Which usually means attending conferences which focus
| on specific diseases.
| andy_ppp wrote:
| You mean the sort of conferences that attract charlatans
| and conspiracy theorists?
| adamredwoods wrote:
| Rare diseases fund research through philanthropy. And let's
| not forget Biden's Cancer Moonshot program!
|
| https://www.whitehouse.gov/cancermoonshot/
| insane_dreamer wrote:
| Medical trials to prove its safety in human subjects -- pretty
| essential -- is a lengthy, multi-stage process that is
| extremely expensive to carry out.
| Panzer04 wrote:
| One must wonder if the therapy works if it's as trivial and
| simple as you say.
|
| Rarely are these things straightforward and clear cut.
|
| That being said, I recently broke my ankle, and found that the
| protocols still often include 6 weeks off it, despite modern
| evidence largely showing zero downsides (and some benefits,
| especially in terms of early recovery) to weight bearing
| immediately - Probably costing possibly billions of dollars in
| lost productivity and unnecessary PT every year.
|
| I probably shouldn't get too high on my horse about random
| unexplored therapies - plenty of things in medicine that are
| just done some way because that's how it's always been done.
| adamredwoods wrote:
| When my wife was alive, some people in her group tried it.
| There's not much evidence.
|
| >> that have promising anti cancer effects
|
| I don't know why people gravitate towards the "simple" remedies
| for cancer, or pose that money making is a barrier for these
| remedies. Remember, research costs money! DO the funding
| yourself if you think there's a miracle cure here. (hint:
| there's not.)
| jdhendrickson wrote:
| I am sorry for your loss, you lived through my biggest fear.
| It must be so frustrating to read this kind of thing over and
| over.
| cyberax wrote:
| > That's interesting. I was just reading about how high dose IV
| vitamin c can induce cell death in a wide variety of cancers,
| but somehow, despite this being known for decades, nobody has
| done rigorous research on it.
|
| Sigh. Vitamin C quackery again.
|
| Vitamin C at high doses is cytotoxic, so it works against
| rapidly dividing cells. Cancer cells also preferentially
| concentrate vitamin C because they are under oxidative stress.
|
| However, just like with most of other generally cytotoxic
| treatments, cancer cells quickly evolve resistance to it. And
| the overall toxicity of vitamin C makes it uninteresting as a
| treatment.
| akoboldfrying wrote:
| Thanks for providing a plausible explanation. Do you know of
| any links (ideally peer- reviewed research) supporting the
| quick evolution of resistance to vitamin C? If not I'll
| google around.
| cyberax wrote:
| That's a generic cancer resistance mechanism. That's why
| most of cancer treatments fail eventually, the cancer cells
| evolve to tolerate the levels of chemotherapy agents that
| are lethal to regular cells.
|
| In the articles linked in this thread, large-dose vitamin C
| prolonged survival, but didn't clear the cancer. It's
| exactly what you'd expect from a chemo treatment.
| mahkeiro wrote:
| This was just published by UI showing a potent effect of high
| dose vitamin C + chemotherapy:
| https://medicine.uiowa.edu/content/high-dose-iv-vitamin-c-
| pl... and https://www.sciencedirect.com/science/article/pii/S
| 221323172...
| cyberax wrote:
| That's actually pretty interesting. Pancreatic cancer is
| one of the most aggressive cancers, and without many
| therapeutic options. Vitamin C is basically another drug to
| complement the existing standard-of-care drugs. Not a
| silver bullet, but definitely helpful.
| pfdietz wrote:
| There is evidence that high doses of antioxidants can make
| cancer _worse_ , probably because cancer cells are under
| oxidative stress.
|
| https://www.cancer.gov/news-events/cancer-currents-
| blog/2015...
|
| https://pubmed.ncbi.nlm.nih.gov/8127329/
| cyberax wrote:
| Vitamin C in large doses becomes a pro-oxidant because it
| reduces metal ions, and they in turn then become catalysts
| for oxidative reactions or even directly oxidize stuff.
| shepherdjerred wrote:
| It's pretty unlikely that this is true for a few reasons:
|
| - Doctors want the best outcomes for their patients. They'll
| use whatever treatment is most effective
|
| - Doctors want the best outcomes for themselves. If they've
| found an effective treatment that others are overlooking then
| they'll seek to publish
|
| - Patients want the best outcomes for themselves. If there is
| an overlooked treatment then they'll communicate it to their
| doctor
|
| it's unlikely for an effective treatment to exist and be
| ignored by the medical community for decades just because
| something can't be patented
| DrScientist wrote:
| > Doctors want the best outcomes for themselves. If they've
| found an effective treatment that others are overlooking then
| they'll seek to publish
|
| However often the work required to prove something is
| effective is beyond a capacity of a single Doctor. Also in
| terms of wanting the best outcome for themselves - sometimes
| that involves not putting their career at risk by trying
| unproven treatments on patients ( you are focussing on the
| outcome when it works, not the more likely outcome and
| consequence of it not working ).
|
| So sure 'miracle' cures are unlikely to lay undiscovered -
| but most improvements in medicine are incremental, rather
| than miraculous.
| shepherdjerred wrote:
| I don't disagree with anything you're saying. But it sounds
| like the parent said there's a miracle treatment that the
| medical community is ignoring for lack of a financial
| incentive (and they then go on to mention a financial
| incentive?)
| NotGMan wrote:
| >> If there is an overlooked treatment then they'll
| communicate it to their doctor
|
| Hah sure.
|
| Try this and tell me how the egomanical "gods in white"
| react.
|
| Go through some stuff the RFK says about vaccines etc... and
| you'll see that in real life it's the opposite.
| shepherdjerred wrote:
| I'm not saying all doctors are perfect or even good, but
| surely there would be at least some occasions where a
| patient tries this supposedly very effective treatment,
| gets better, and the doctor is left curious.
| wat10000 wrote:
| The only thing you should take away from the stuff RFK says
| about vaccines is that RFK is a complete kook.
| dennis_jeeves2 wrote:
| Very wrong on all 3. It's an extremely naive world view.
| triceratops wrote:
| Please explain to us all why glory and survival aren't more
| effective motivators than the money to be made from
| patenting something.
| dennis_jeeves2 wrote:
| Things simply don't work that way. It cannot be
| explained, it has to be experienced.
| triceratops wrote:
| I was speaking from experience.
| dennis_jeeves2 wrote:
| No, not your personal experience, but the experiences of
| the others. For example look up Linus Pauling's writings
| on the subject, and the writings of his detractors. Spend
| atleast 50 hours on it.
|
| Also see my post on the same thread:
| https://news.ycombinator.com/item?id=42266462
| shepherdjerred wrote:
| What do you think is correct instead?
| dennis_jeeves2 wrote:
| > - Doctors want the best outcomes for their patients.
| They'll use whatever treatment is most effective.
|
| They will often do what make them the most money. Also
| remember that is doctor is subject to rules and
| regulations. He risks loosing his license if he does not
| toe the line. Your average medical student is about half
| a million dollars in debt when he/she graduates.
|
| > - Doctors want the best outcomes for themselves. If
| they've found an effective treatment that others are
| overlooking then they'll seek to publish.
|
| Doctors do want the best outcomes for themselves, but if
| you manged to become a doctor, it means that you have
| never learned to question authority. Many doctors believe
| that what they are taught is Gospel. A doctor or a
| medical student who questions authority, will either not
| make it through medical college, or will have a license
| revoked.
|
| >- Patients want the best outcomes for themselves. If
| there is an overlooked treatment then they'll communicate
| it to their doctor.
|
| A patient is generally ridiculed, or ignored by the
| doctor if he suggests something that he thinks is better.
|
| It goes without saying that there are exceptions both
| among doctors and patients.
| jamieplex wrote:
| Either you are not from the USA, are trolling, or don't
| really know the U.S. medical system. Yes, maybe a few
| private practice doctors are greedy, but generally,
| doctors "in the system" don't personally generate more
| funds by doing things different, prescribing more drugs,
| etc. They are on salary. As far as other types of doctors
| (eg. chiropractors), they DEFINITELY drive home more
| money by prescribing more, requiring return visits, etc.
| But I call them doctors only by the loosest of
| definitions.
|
| I am baffled by your second paragraph. It is just plainly
| illogical.
|
| The third paragraph tells me that you ARE possibly from
| outside the USA, or that you have only seen a few doctors
| and they were proud or rude. We (personally) have seen
| private doctors, hospital doctors, country doctors, etc.
| over 50 years (at least 50-60 different ones). And the
| preponderance of our evidence shows you are either
| misinformed, or you are a patient who wants to self
| prescribe treatments that are medically unsound or
| 'fringe'. And, yes, those WILL be ignored by any average
| doctor. But then you could always fly to Mexico and get
| those useless treatments for low cost...
| dennis_jeeves2 wrote:
| All I will say is this: We have different assessments of
| the situation. And yes I do live in US.
|
| Some of what you point out is correct: Most doctors are
| on salary, but they are often (implicitly) required to
| bring in more business by the organization they work for.
| If they don't, they risk loosing their license/job on
| some pretext. In totality what I said overall hold true.
| These are statements from the renegade doctors
| themselves. Of course you are going to dismiss them as
| fringe, quacks etc.
|
| Labeling someone is a fringe and easy way to dismiss
| them, it does not involve any work. What time have you
| spend listening to these fringe MDs? What time have you
| spent examining their patient outcomes/reports? Any yes,
| it goes without saying one has to be discerning even
| among the fringe MDs.
| alphan0n wrote:
| Bullets can induce cell death in a wide variety of cancers as
| well.
|
| https://xkcd.com/1217/
| pjc50 wrote:
| This dates back to Linus Pauling:
| https://lpi.oregonstate.edu/mic/vitamins/vitamin-C/pauling-r...
|
| It seems that once you exceed a certain level the body just
| dumps it, making megadoses unviable.
| pfdietz wrote:
| You get nicely expensive urine, though.
| dennis_jeeves2 wrote:
| >That's interesting. I was just reading about how high dose IV
| vitamin c can induce cell death in a wide variety of cancers,
| but somehow, despite this being known for decades, nobody has
| done rigorous research on it
|
| Linus Pauling (of the Nobel Laureate fame) working along with
| some physicians did do 'rigorous' research on it, and I think
| had published a book on it. You should be able to check the
| Linus Pauling Institute and find literature on it. I probably
| did it over a decade back. Predictably he was ridiculed (IMO
| wrongfully) for it by people who did a very shoddy job of
| looking into the nuances.
|
| The last I checked in the US the Riordan clinic offers Vit C
| for Cancer. There are probably several other practitioners who
| will not publicize that they treat patients for cancer (and
| several other chronic conditions) for obvious reasons.
| ALittleLight wrote:
| Deeply disappointed by the comments replying to this. I would
| reply to each individually, but feel like I'd get throttled by
| hackernews, so I'll just reply to everyone here.
|
| ---
|
| shepherdjerred writes that this is unlikely because doctors
| want what is best for their patients and would notice a cure
| were it available.
|
| This is kind of true. Some doctors do know about and prescribe
| vitamin c with typical therapy. Here is an umbrella review of
| hundreds of such cases documenting positive results from using
| vitamin C.
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC8812486/
|
| The issue is not whether doctors will prescribe it - I expect
| anyone could ask their doctor for it. Vitamin C is safe, well
| tolerated, and shown to mitigate symptoms of chemotherapy.
| Doctors can and do prescribe it.
|
| The issue is why an apparently promising therapy isn't getting
| better testing to establish whether or not it is effective
| despite it being known for decades.
|
| ---
|
| adamredwoods writes that while his wife was still alive people
| in her group tried it.
|
| I'd love to know more - especially type of cancer and whether
| the vitamin c was administered orally (no effect expected) or
| by IV (depending on type of cancer possible effect expected)
| and at what dosage.
|
| Here's a randomized controlled trial showing substantial
| benefits of high dose IV vitamin C for patients with advanced
| pancreatic cancer - they live longer, the cancer progresses
| slower, and their quality of life is generally better.
|
| https://pubmed.ncbi.nlm.nih.gov/39369582/
|
| Adam goes on to suggest I should do the funding myself if I
| think there is a miracle cure here.
|
| There are a couple ideas here. If I or a loved one ever develop
| cancer - then of course (depending on type of cancer) I would
| take high dose IV vitamin C, along with similar therapies that
| are well established as safe and potentially useful.
|
| As far as "Doing the research myself" - honestly, I might. My
| path would be to construct a website compiling the research,
| explaining why people with cancer should try this, explaining
| how you can get your doctor to prescribe it to you (or, since
| you don't need a prescription to take vitamin c, how you can
| DIY), and have functionality to support people registering that
| they are a cancer patient who has decided to take vitamin c (or
| not) and give updates.
|
| The hope with the website would be that it could compile enough
| raw data to become compelling to medical professionals.
|
| ---
|
| Panzer04 asks "if the therapy works if it's as trivial and
| simple as you say" - why isn't it being done?
|
| Vitamin C _is_ sometimes used. That 's why we have hundreds of
| case studies and, in some cases, randomized controlled trials
| and other experiments documenting its use and efficacy.
|
| My comments here aren't based on what I say or think - my
| original source was an article explaining the research on
| cancer.gov. Vitamin C (again: high dose and IV administered) is
| known to have potential benefits for cancer patients.
|
| ---
|
| cyberax says "Sigh. Vitamin C quackery again" and then offers a
| partial explanation of the mechanism for how vitamin C causes
| cell death in cancer cells - which is better explained in the
| link I originally provided.
|
| cyberax then claims, without evidence, that cancer cells
| quickly evolve resistance to it. I don't believe there is any
| such evidence, having read several papers on this and never
| seeing it mentioned - nor, by my understanding, is it plausible
| that cancer cells could fundamentally change how they work to
| get immunity to this. Perhaps I'm wrong though and cyberax
| could supply some evidence.
|
| I notice in the replies to cyberax pfdietz says "There is
| evidence that high doses of antioxidants can make cancer worse"
| - and then links 2 papers exploring the use of vitamin E as a
| cancer treatment. Vitamin E, despite sharing quite a few
| letters with Vitamin C, is a different thing.
|
| ---
|
| dennis_jeeves2 writes that "Linus Pauling (of the Nobel
| Laureate fame) working along with some physicians did do
| 'rigorous' research on it".
|
| This is not correct and explained in the first few paragraphs
| of my original link. Linus Pauling used _orally_ administered
| vitamin C which results in weaker blood concentrations and
| therefore less impact on cancer. The modern method uses _IV
| administered_ high dose Vitamin C (which I was careful to write
| in my comment).
|
| While Pauling's method shows little effect in randomized
| controlled trials, high dose IV Vitamin C does show benefits.
|
| ---
|
| insane_dreamer writes that "Medical trials to prove its safety
| in human subjects -- pretty essential -- is a lengthy, multi-
| stage process that is extremely expensive to carry out."
|
| Pretty meaningless comment. The safety of vitamin C is already
| well established.
|
| ---
|
| pjc50 also cites Linus Pauling - which, again, is explained in
| the first couple paragraphs of the link I originally posted.
| High dose orally administered vitamin C doesn't work - there
| are limits on how much you can increase blood concentration
| through oral administration, so most of the high dose is lost.
|
| That's why, as explained in my original comment/link, the
| modern protocol uses IV administered vitamin C.
|
| ---
|
| alphan0n quotes an XKCD strip saying "Bullets can induce cell
| death in a wide variety of cancers as well."
|
| A bad comment because the tests I've been linked to have been
| in vivo, and my original link explains why this kills cancer
| cells and not healthy cells.
|
| ---
|
| That's my review of the comments. I would characterize them as
| exceptionally uninformed - which is odd. Why would people feel
| the need to comment on a subject they don't know about and
| simultaneously refuse to read the outline I originally linked
| which answers all the questions and criticisms posted here?
| southernplaces7 wrote:
| This is what I call a cogent, measured and robust rebuttal to
| several opposing viewpoints. I don't have much to add as a
| response of my own on the specifics but just want to mention
| that what your comment tacitly points out repeatedly is very
| common in the comments on this site, for many subjects and
| especially those that seem to provoke a certain popular hive-
| mind response:
|
| People writing completely half-baked, often deeply ignorant
| opinions on complex, nuanced subjects out of mostly emotional
| disdain, but phrasing their responses in such a way as to
| easily fool someone who doesn't know said subject well that
| they at all know what they're talking about and are thus
| arguing rationally.
| baranul wrote:
| Case in point, Cuba's lung cancer vaccine[1]. Which a company has
| brought to the U.S. as CIMAvax-EGF[2].
|
| [1]: https://www.usatoday.com/story/news/world/2018/01/09/cuba-
| ha...
|
| [2]: https://www.roswellpark.org/cimavax
| adamredwoods wrote:
| https://aacrjournals.org/clincancerres/article/22/15/3782/79...
| onionisafruit wrote:
| As an aside, what makes this a vaccine vs a treatment?
| spondylosaurus wrote:
| > Neither of the vaccines prevents cancer; rather, they are a
| kind of immunotherapy that prompts the body's immune system
| to battle the disease in patients with non-small cell lung
| cancer.
|
| Not 100% sure, because I've only heard about vaccines in
| preventative contexts before, but based on this description
| my guess would be that "anything that tells your immune
| system to Do Stuff" counts as a vaccine. Versus something
| like Herceptin, which also treats cancer, just with ready-
| made antibodies that were grown in a lab.
| pfdietz wrote:
| There are also immune modulators that aren't vaccines.
| Interferon, for example, or more recently the famous
| checkpoint inhibitors that take the brakes off immune
| attack of cancer cells.
| quantumwoke wrote:
| My wife (MD) tells me that vaccine refers to anything that
| induces an immune response against a pathogen or disease. In
| this case the vaccine causes anti-EGFR antibody production
| JPLeRouzic wrote:
| > _In this case the vaccine causes anti-EGFR antibody
| production_
|
| English is not my native tongue so I have some problem to
| parse your sentence. I prefer the writing in the
| publication cited above [0] even if it's probably the same
| meaning:
|
| " _CIMAvax-EGF is a therapeutic cancer vaccine composed of
| human recombinant EGF_ "
|
| [0] https://aacrjournals.org/clincancerres/article/22/15/37
| 82/79...
| quietbritishjim wrote:
| It parses fine to me, but then I'm a native English
| speaker (and I don't claim to know whether its content is
| actually true). Strictly speaking, there should be a
| comma after "case", which may have helped you but is
| unusual unless you're writing something really formal.
|
| Here's the sentence restructured:
|
| ... vaccine refers to anything that induces an immune
| response against a pathogen or disease. Here is how that
| definition applies in this case: the vaccine causes the
| immune system to produce anti-EGFR antibodies.
| EternalFury wrote:
| Anyone can mix chemicals in a test tube and claim it's the cure
| for something. That's the easy part. Proving it's safe and
| effective, that's what requires a lot of capital expenditure.
|
| This statement is a drastic characterization, but you could say
| "half a dozen PhDs can form reasons to believe they may have
| found a cure for something", and the paragraph would end the
| same.
| cchi_co wrote:
| Discovery is just the tip of the iceberg
| vasco wrote:
| Since these are cancer trials I'm assuming no test subjects get
| paid, and university PhDs research for free, like in every
| other field, so what necessarily has to be expensive about it?
|
| If you have to pay 200 homeless to take your 0.0001% better
| than placebo antidepressants in the context of a huge
| corporation, and maybe redo the trial a few times, I can see
| how that gets expensive, but I don't see why it's a de facto
| rule.
|
| But even the big trials it's weird how expensive people say
| they are. Most other products require a lot of high paid labor
| to produce, think of a video game studio for example, also
| without any guarantee it won't flop, and it certainly takes
| longer to develop than to do a clinical trial.
| rahkiin wrote:
| PhD candidates are paid salary in the Netherlands. Less of
| course than the senior trial researchers at pharma. I also
| would not assume there is no compensation for subjects as
| thats part of the medical-ethical process and not just 'it
| helps the subject so no money'.
| vasco wrote:
| The EUR30k to EUR35k per year they make in this context
| approximates to free. Any normal company has to pay much
| more than that for less. A non-phd software engineer will
| get paid much more to change button colors for example. So
| that can't be the reason they are expensive and a PhD
| candidate is doing many other things than just helping to
| run trials.
| JPLeRouzic wrote:
| > _Any normal company has to pay much more than that for
| less_
|
| In most EU countries, the employee receives much less
| than what they cost the employer. In France, if an
| employee gets 30K euros, the employer has to provision
| ~45K Euros.
| vasco wrote:
| What's your point? I've lived in 3 different european
| countries, I'm familiar with fully loaded costs, I don't
| see how social security changes anything. By paying more
| for less I mean PhDs candidates are very cheap labor for
| what they bring to the table.
| StefanBatory wrote:
| Also as much as it pains to say, 30-35k Euro is high
| salary there. :(
| monero-xmr wrote:
| This is the most misinformed unknowing take in all of the
| comments.
|
| You can't just recruit "200 homeless" and have it pass
| research standards. The homeless population is the most
| difficult of all to track, maintain accurate records, and
| even recruit for that matter. You think the homeless just
| line up for novel drug trials and report back for updates on
| a strict schedule?
|
| You need good candidates for the trial. You need them to
| follow up. You need admins to properly track them and ensure
| it's at least mostly accurate. Even the best trial candidates
| won't follow the protocol correctly.
| vasco wrote:
| I invite you to read
| https://www.researchgate.net/profile/Carl-
| Elliott/publicatio...
|
| If you genuinely think the medical and pharma industry
| don't exploit homeless and other marginalized populations
| out the wazoo as lab rats. They also only stopped doing it
| to prisioners when it was made illegal, because that's what
| they did before. Of course using them has a lot of
| practical problems, as you outline, other than the much
| bigger ethical issue.
|
| You managed to miss the whole point of the comment though.
|
| Which is, how is it possible that a multibillion dollar
| industry, exploiting both the test subjects AS WELL as the
| researchers in the form of practically free PhD candidates
| can still claim it's one of the most dificult / expensive
| endeavours? Where does the money go? When you look, it goes
| to the bureocrats and to the "bio-investors".
| pfdietz wrote:
| I (not homeless!) was recently in a vaccine trial
| (Moderna's mRNA vaccine for RSV). The trial paid me $100
| per office visit, just to show up. There were periodic
| phone checkups ($50) and a weekly status check through an
| app ($10). I did follow the protocol pretty damn well.
| There was an incentive to come in and get checked when
| symptoms occurred, including when I came down with COVID at
| one point after a trip to Europe.
| robertlagrant wrote:
| > Most other products require a lot of high paid labor to
| produce, think of a video game studio for example, also
| without any guarantee it won't flop, and it certainly takes
| longer to develop than to do a clinical trial.
|
| You have to try really hard to make a video game no-one
| wants[0]. You might not recoup all your investment, but you
| won't sell zero copies. A drug can have all that money poured
| in, and nothing come of it.
|
| [0] https://arstechnica.com/gaming/2024/09/two-weeks-after-
| launc...
| vasco wrote:
| https://247wallst.com/media/2024/08/04/9-biggest-video-
| game-...
| robertlagrant wrote:
| There is certainly a difference between profit and
| revenue, yes.
| vasco wrote:
| I guess it's easier to casually mention you might not
| recoup your investment when it's not your $200mil but my
| point it's just that there's a lot of speculative
| technical research or cultural output that is very hard
| to predict outcome, some of these things also requiring
| high paid labor, and we don't have a huge thing around
| "omg if they don't all become billionnaires selling drugs
| nobody will make drugs because it's so hard and
| expensive", meanwhile people are going to space and so
| on.
| InDubioProRubio wrote:
| Does it? There is a billion people on this planet without
| adequate medical system - whose health is not considered worth
| investing into. If they get auto-diagnosed by app (zero-cost),
| they could volunteer for a free chemical trial (delivery of
| package), a application of said package (local nurse - not
| free) and a series of follow up scans + analysis.
|
| The office behemoths involved are optional. Whats missing is
| tools to scan the body locally for cheap. The rest can be
| automated or distributed to people with an interest in success
| (high-level-analysis by the cure developers).
|
| Here are the volunteers:
| https://www.sciencedirect.com/science/article/pii/S266700542...
| llamaimperative wrote:
| Lovely: so just give tons of people an experimental drug and
| collect garbage data by doing so!
| bilbo0s wrote:
| I'm not sure people fully understand the scientific method.
|
| All data is not reliable data.
| wesselbindt wrote:
| > whose health is not considered worth investing into. If
| they get auto-diagnosed by app (zero-cost), they could
| volunteer for a free chemical trial
|
| What a profoundly ineffective and broken system we have that
| this could be uttered as anything other than satire.
| InDubioProRubio wrote:
| So the perfect nothing is allowed to block the imperfect
| something, because we wait for humans to transcend to
| angelic beeings?
| wesselbindt wrote:
| Yeah, not doing human testing on poor folks without a
| choice is really "angelic" and "perfect". Very high bar
| to set, how could we possibly achieve such high standards
| of morality?
| InDubioProRubio wrote:
| They have a choice. To use the medicine or not. The
| choice is gone in the other case- where you can die of
| cancer for "ethical" comission reasons.
| jodleif wrote:
| That's essentially a non-choice. Also data of self-
| administration is probably worthless.
| nkrisc wrote:
| I'm inclined to believe that the status quo is actually
| better than mass human experimentation on the poor.
| InDubioProRubio wrote:
| PS: Yes, its a deeply broken system- and its also on the
| point where the well-off blue blooded caste starts to blame
| the lower-classes for the misery inflicted upon them again-
| aka, if you are of low blood, you are obviously lazy
| because you spend so much time in bed being sick. Ideology
| can be a very effective tool to deactivate compassion.
| ano-ther wrote:
| From the article translation it sounds like they have phase 3
| data and submitted or are about to submit an application to the
| European Medicines Agency.
|
| That means they have gone all the way to prove it's safe and
| effective, and now have to convince the regulators.
|
| Can anyone find the studies?
| null08 wrote:
| https://www.nejm.org/doi/full/10.1056/NEJMoa2402604
| null08 wrote:
| This article is about a phase III RCT that the hospital managed
| to do without major industry capital injection. This truly was
| a major achievement (I have been involved in a phase III RCT
| myself). It was published in the New England recently:
| https://www.nejm.org/doi/full/10.1056/NEJMoa2402604
| kijalo wrote:
| This trial is using an existing drug in a potentially novel
| way (before surgery as opposed to after surgery). I dont
| think it really lives up the original article title.
| Gokevin wrote:
| Supported by Bristol Myers Squibb;
| refurb wrote:
| The article literally says "Funded by Bristol Myers Squibb
| and others".
| null08 wrote:
| Argh, I'm so sorry, I linked to the wrong New England paper
| in my post above. (That is a different major achievement from
| the same institution, but the above was industry funded as
| others correctly pointed out).
|
| The correct New England paper about this treatment is here:
|
| https://www.nejm.org/doi/10.1056/NEJMoa2210233
|
| This one is TIL therapy, where you basically take tumor-
| infiltrating lymphocyte from the patient, stimulate them ex
| vivo, and put them back.
|
| The reason this is so impressive -- and highlighted by this
| article -- is that large phase III trials like this have now
| become so complicated due to various technical, financial,
| logistic, ethical, and above all regulatory challenges, that
| they are now mostly done by companies, or at least as joint
| ventures with companies (and often in jurisdictions with less
| of these issues, certainly not in the EU like this one). It
| is very, very impressive to pull off something like this as
| an academic institution (at least in Europe). What's more,
| the funding came from KWF (the Dutch cancer foundation),
| which is actually a public charity that mainly relies on
| donations.
| ramraj07 wrote:
| Got my PhD from a lab that works on antibody drugs, they
| eventually even released one to the market.
|
| I'd argue that our current system is broken. There's no
| reliable metric of drug effectiveness in any of our pre-
| clinical models, and thus we end up going into clinical trials
| quite blind indeed. And more often than not, what drug gets
| into trials has more to do with ego and politics than actual
| scientific merit. And the folks involved in these types of
| activities are (IMO) the most unoriginal types I've ever seen.
|
| There's a lot we can do to improve our drug development
| process. It really doesn't need to cost billions to bring a
| drug to the market. But the odds are stacked against anyone
| with a contrarian hypothesis and I just figured I'd save my
| sweat and leave this field instead.
| prox wrote:
| Is this a market that can be disrupted? It sounds if you know
| how to save a few billion and introduce more science based
| drugs, it's ripe for an overtake.
| DrScientist wrote:
| In the same way Uber disrupted licensed taxis - or the big
| internet firms disrupted ad supported media.
|
| ie totally ignoring existing regulations, pretending they
| don't apply to you and just hoping you can push through.
|
| In a lot of the 'problems' are the regulations ( which are
| double edged and tricky to get right ) - and pharma
| companies are just following the rules.
|
| I think governments might be less lax in letting there be a
| new wildwest in drug development.
| llamaimperative wrote:
| Pointing the finger at regulation is misleading IMO. The
| regulations for bringing a drug to market are essentially
| quite simple: prove that it's better than what currently
| exists.
|
| What makes it difficult is the word " _prove_ "
|
| It turns out it's obscenely hard to make a drug that's
| good, and even harder to prove that it's good.
| DrScientist wrote:
| > prove that it's better than what currently exists.
|
| So how do you do that ethically? How do you justify
| taking off something that you know works to some extent
| and try something completely new or worse placebo? ie
| don't you have to construct the trial in the context of
| existing treatments etc?
|
| These are the kind of challenges that makes drug
| development slow - in the end you don't do one trial, but
| a series of trials, slowly building confidence and making
| the case.
|
| Often that's what takes the time during the clinical
| phase.
|
| Of course it would be much faster to go straight to a big
| trial that would show how well your treatment works in
| conditions optimal to it - however that kind of 'move-
| fast break-things' approach involves potentially breaking
| things which happen to be people.
|
| Regulation just reflects the cautious 'first do no harm'
| philosophy.
|
| Now let's be honest - big pharma will simultaneous
| complain about regulation and the cost of development,
| and at the same time know it creates barriers to entry -
| there is always some frustration about the slowest of
| regulatory authorities to adopt new methods - however you
| wouldn't want your regulatory to be gungho.
| datavirtue wrote:
| Inmates. Go wild. For some reason this abhores the
| intellegencia while myriads of innocent rodents get
| tortured.
| DrScientist wrote:
| Purdue Pharma, fentanyl and doctors abrogating
| responsibility for patient safety is an example of 'go
| wild'.
|
| On your second point - I'd agree that a lot of animal
| experiments are not that informative - but lets be clear
| 'clinical trials' are simply experiments on people.
|
| I'm not sure I'd want to give Musk, Zuckerberg or Bezos
| free reign to experiment on desperate people in the
| medical space.
|
| Depends on whether you treat people as just grist to your
| money making mill - or perhaps you think the ends justify
| the means?
| wat10000 wrote:
| Sorry, are you having difficulty with the concept that
| human prisoners should have more rights than mice?
| rflrob wrote:
| > or worse placebo
|
| Just to be clear, most drug trials for anything where we
| have an effective treatment are not "new drug vs
| placebo", but instead "new drug vs standard of care".
| Thus the goal being to prove it's better than what
| already exists.
| DrScientist wrote:
| Sure - it rather depends on how good the 'standard of
| care' is or how much consensus there is on what that
| should actually be.
|
| If the standard of care is already good and you don't
| need a placebo - then you have another problem - you
| probably are going to have to do quite a big trial to get
| the stats to show a significant difference, and you are
| going to find it harder to persuade people to participate
| with an experimental treatment if there already is a
| fairly good treatment.
|
| The whole point about the challenges with clinical trials
| is that it's not an intellectual exercise in designing
| the perfect experiment and 'just doing it'.
|
| It's about persuading yourself, the regulators, the
| doctors and ultimately the patients that it's something
| you should try - and before you've done your first trial
| you don't have any human data to show it's safe and
| effective - all a bit chicken and egg - the solution is
| often to move slowly in stages.
| adventured wrote:
| There's no hoping you can push through. The US Government
| has complete top-down control over the sale of
| prescription drugs in the US, from clinicals to approval
| to distribution & sale.
|
| The sole reason Uber pulled off what they did, is there's
| no national authority governing taxi style services for
| all states and cities, it's a state and local effort. So
| Uber counted on navigating around zillions of slow local
| governments long enough to get big, and it worked very
| well. You can't do that in prescription drugs, the feds
| have a big hammer and can (and will) use it anytime they
| like.
| jorvi wrote:
| Uber disrupted taxis because taxis were a sleazy
| experience, with dirty old cars, "broken" meters and rude
| drivers that tried to get you to pay extortionate prices
| if they knew you were in a pinch.
|
| Stop trying to venerate the taxi industry, they're
| horrible.
| DrScientist wrote:
| I think that depends on what part of the world you live
| in.
|
| My experience of taxi companies in the UK is that they
| are generally safe, reliable and operate based on
| reputation.
|
| My experience of taxi's in the US is that they appear to
| be often operated by desperate people living on the edge
| of existence.
| immibis wrote:
| Isn't that every service in the US? It takes pride on
| pushing the under people to the brink of death.
| ramraj07 wrote:
| Absolutely, and if you recall, even YC tried to get in on
| this idea.
|
| Except they did the same mistake anyone who comes up with
| this disruption plan commits (including Google with Calico,
| or Zuck with CZI) - they recruit existing academics to do
| the disruption. Unfortunately this just fails miserably
| because they're culturally corrupted to think of standard
| dogmas (like there can never be a single cure for cancer).
| I remember a time when other such dogmas existed (remember
| how it was considered impossible to de-differentiate
| somatic cells?).
|
| The other mistake tech bros make in biology is they think
| they can make any cool idea work if they are smart enough.
| Because this is actually true in tech. But biology is
| restricted by laws of nature. If a drug doesn't work, it
| can't be made to work. There's no room for wishful
| thinking.
|
| Third mistake I see often is individual bias towards fields
| that they come from. Someone who has an RNA background will
| only try to use RNA to solve everything, likewise with
| antibodies, or imaging, etc. The current research funding
| system incentivizes such thinking and it becomes entrenched
| in anyone already in this field. There's never a thought of
| "which is the exact technology and approach I should use to
| solve this problem independent of what I'm an expert at?"
| So a lot of projects are doomed from the start.
|
| As long as you're cognizant of these three facts, I think
| it's very possible to disrupt this field.
| nradov wrote:
| Is there any plausible biological reason to think that
| there could ever be a single cure for cancer?
| ckemere wrote:
| Perhaps immune-based therapies like CAR-T are based on
| the premise that there are many cancerous cells in your
| body all the time, but your immune system deals with
| them, and it's only when it fails to do so that you end
| up in the pathological state. So the "single cure" is the
| normally-functioning immune system?
| nradov wrote:
| That might be part of it. And yet sometimes people with
| normally-functioning immune systems also get cancer. So
| while that might be an effective treatment for some
| patients it's not going to be a universal cure.
| inglor_cz wrote:
| Human "normal" may not be enough.
|
| Bat "normal" might be. Of course, now we are crossing the
| threshold from medicine to bio-augmentation.
| nradov wrote:
| There is no free lunch in biology. Augmenting the immune
| system to better attack cancer is going to cause other
| problems. It's so naive to think there is some simple
| solution that will improve on a billion years of
| evolution. I mean it's not _impossible_ but realistically
| what are the odds?
|
| There won't be any magic for cancer. It's just going to
| be slow grind to solve one hard problem after another.
| inglor_cz wrote:
| Some mammal species like bats, whales and naked mole rats
| seem to be extremely unlikely to get cancer. Which may be
| an indication that a very efficient immune system can
| keep cancer in check indefinitely.
| DrScientist wrote:
| I'd agree with a lot of that in terms of both many drugs
| being 'discovered' in clinical trials as oppose to earlier (
| a lot of it it about choosing the right patients and dose ),
| and the differences in mindsets between researchers and those
| often involved in the clinical trial side.
|
| One of the things you've missed is the strong restrictions
| put on pharma in terms of promoting use of existing drugs
| beyond the existing approval ( which makes sense ), and the
| almost complete freedom Doctors have to do what they want -
| they can just decide to prescribe something off-label if they
| think it might help.
|
| It can take a very long time for new ideas to become new
| products - and a lot of that is inertia ( nobody else is
| doing it ).
| raxxorraxor wrote:
| I think the restrictions on pharma, while doctors have more
| freedom is quite helpful. There are some problems here as
| well where this freedom has been abused, but overall that
| isn't a problem in my opinion.
|
| Clinical trials are long and expensive, the medical
| advisory board wants compensation as well. But even
| startups can theoretically fund new therapies if they and
| their medial advisory boards get subsidies. It is a lot of
| risk though because for most drugs or medical devices, the
| real effectiveness can only be determined later in the
| trial itself.
| JPLeRouzic wrote:
| Many thanks for saying what I suspected when looking at the
| research publications and clinical trials on
| neurodegenerative diseases. I was starting to think I was an
| unproductive perpetual malcontent.
|
| For example, memantine has been tested 5 times in ALS. There
| even no pre-clinical studies that show any positive effect of
| memantine in animal models. This seems so bizarre to me.
| pfisherman wrote:
| How good are our animal models of ALS? Are they predictive
| of effectiveness in humans?
| JPLeRouzic wrote:
| I am not an expert (I am a retired R&D telecom engineer)
| but here is my take:
|
| * As for cancer, there are several (many?) ALS variants.
| The first gene to be associated with ALS was SOD1 G93A
| allele in 1993. It stayed the only ALS gene known until
| 2006. That was a curse for research as ALS with SOD1
| origin is less than 2% of total cases, and even for SOD1
| there are dozens of mutations associated with ALS, some
| with 6 months of life expectancy, others with 20 years.
|
| * Most commercial animal models are SOD1 G93A mice [0].
| The G93A mutation represents roughly only 0.4-1.4% of all
| ALS cases worldwide, yet it is the most used animal
| model!
|
| SOD1 G93A ALS models are also the less costly animal
| models.
|
| * I think another important thing is that ALS starts
| often in hands (split hand phenomena) and targets
| skeletal muscles. But humans' nervous system for hands is
| very special, only shared with other upper primates.
| Other mammals like mice have an interneuron between the
| upper and lower motor neuron for hands. We do not, there
| is a direct connection between upper and lower motor
| neurons, reflecting the importance of manipulation for
| humans. Therefore for me, we can't prove with mice at
| pre-clinical stage, that a drug is efficacious or not
| (many drugs have some efficacy in animal models, but none
| in humans).
|
| * Some publications pretend they can use individual
| cells, fishes, or nematodes as animal models. That's
| laughable, it's ignoring the importance of anatomy and
| physiology. We are complex animals, our hormones, our
| immune system, and our metabolism are important to
| understanding ALS. The proof of that is that ALS patients
| who have the best life expectancy have a BMI of 27.
|
| * Other publications pretend to make their own animal
| models with some chemical, like BMAA, a neurotoxin found
| in certain cyanobacteria. Those publications smell bad
| behavior for me.
|
| If you want to buy a mice model of ALS:
|
| [0] https://www.jax.org/jax-mice-and-
| services/preclinical-resear...
| pfdietz wrote:
| The current system is like Churchill's description of
| democracy: the worst system, except for all the others.
|
| Biology is extremely complex. There's no substitute for
| actually trying things out on subjects in vivo. For many
| diseases we don't even know the cause (Alzheimer's for
| example). Drug companies have all the incentive in the world
| to improve the system to get better odds; it's not like they
| _want_ drug discovery to be such a crapshoot.
| clooless wrote:
| We also don't understand how some drugs work, either (e.g.
| Tylenol).
| pfdietz wrote:
| A utility-maximizing drug discovery system would, I
| think, devote some effort to biological experimentation
| on healthy humans, giving them chemical probes to see how
| that affected their biology. As is, ethics requires we
| get this information accidentally, for example from that
| famous recreational drug chemist who gave himself
| Parkinson's Disease with a botched synthesis that made a
| highly neurotoxic chemical. And some of the information
| comes from drug trials. A useful drug is not the only
| value obtained from a drug trial -- each trial is also a
| test of a hypothesis about the mechanisms of a disease.
|
| One of the books of the "Colossus" trilogy (about a
| computer that takes over the world) had the computer
| doing this sort of medical experimentation on randomly
| selected drafted subjects, with the idea of maximizing
| overall utility. It shows the problem with utility
| maximization as a goal, similar to the requirement that
| people give up a healthy kidney if someone else needs a
| transplant.
| cess11 wrote:
| I'd say we have a rather good idea about the mechanisms
| for pain relief from paracetamol. Even Wikipedia has a
| decent summary: https://en.wikipedia.org/wiki/Paracetamol
| #Pharmacodynamics
| mft_ wrote:
| It doesn't (have to) cost billions to bring a (successful)
| drug to market.
|
| And if you pick a single successful example that was
| discovered in academia, was spun out into a small focussed
| biotech, and was in a disease area that didn't require large
| or multiple studies to make it to market, you'll have your
| anecdote to prove your point.
|
| Except... you'd be ignoring the costs of the 90% of drugs
| that fail in phase 1. You'd be ignoring the huge amount spent
| on discovery across the industry that never leads to a
| successful candidate.
|
| Drug discovery and development is difficult because, for all
| of our clever science, it's still essentially serendipitous
| and random. And we've not yet figured out how to make a
| production line out of something that's random, try as we
| might. And it's expensive because of the failures as well as
| the cost associated with success.
| fragmede wrote:
| Right. You can't just choose to run the successful clinical
| trials anymore than you can choose to only buy stocks that
| will go up on wall street. you have to run various clinical
| trials for a drug, and they fail. a lot. that very very
| expensive with no payoff. the successes have to be so
| phenomenally profitable that they cover the costs of all
| the failures. So real change would come from making the
| costs of those failures go away, without being able to
| cheat the system. The amount of medicine is believed to
| work, but is unpatentable, and thus doesn't have the profit
| motive to be pushed through clinical trials is a huge black
| badge on the American version of capitalism as being the
| best way we can organize society for the advancement of
| science and technology.
| evantbyrne wrote:
| Some drugs not being able to make it into phase 1 clinical
| trials sounds like a functioning regulatory system to me. The
| bar isn't astronomically high for a phase 1. Like sure, you
| can't just do it in your garage like a web startup, but there
| are reasons for that. If anything, there are way too many
| drugs floating around in LDT right now, hence why those are
| being faded out.
| Joaomcabrita wrote:
| There are companies trying to address this right? Have you
| seen biorce and other new ventures? Hopefully it can bring
| some innovation and reform to old processes.
|
| That being said, we're talking about human lives either way
| so it needs to be thought through and avoid unintended
| disasters through lack of care.
| refurb wrote:
| Exactly.
|
| I work in this field. Doing phase 3 clinical trials costs
| between $5,000 to $20,000 per patient per year.
|
| This particular drug did a phase 3 with 423 patients for 2
| years, so you're looking at a cost of $4M to $16M just for this
| one trial alone. Then add on top all the CMC (manufacturing)
| research that needs to happen, the regulatory filing work, etc,
| etc.
|
| Unless someone has a few hundreds of millions sitting around,
| you aren't bringing a novel drug to market without external
| funding.
| yread wrote:
| When hospitals are contracted to do work in a clinical trial
| setting they take their costs and multiply it by 10 (at
| least). This was done in house with in house resources. This
| hospital has its own pharmacy that can synthesize drugs and
| give it to the patients. The pharmacy probably charged just
| the material costs internally and not for the time.
| TheToadKnows wrote:
| Drug development faces a forecasting problem, not a measurement
| problem. In the same way that temperature, pressure, and
| humidity readings have been collected for centuries, it wasn't
| until we developed models and computational power that accurate
| weather forecasting became possible.
|
| Similarly, in drug development, we've long had access to
| extensive pre-clinical data and measurement tools. However,
| without predictive models to interpret this data, we will
| continue to struggle to forecast a drug's safety and
| effectiveness in humans.
|
| Interesting coincidence that for the last several decades, the
| rate of success of a drug advancing from a phase 1 clinical
| trial to approval is about 10%, which was just about how good
| we were at forecasting tomorrow's weather between 1900-1950.
| mistercheph wrote:
| * proving it's safe and effective, *and* getting the go-ahead
| from the drug cartels
| rdruxn wrote:
| To quote xkcd, "So does a handgun" https://xkcd.com/1217/
| s1artibartfast wrote:
| >Drawing up such a dossier is a profession in itself. An
| important detail: the EMA is asking for around EUR350,000 to
| assess the book.
|
| This is a massive understatement of the regulatory hurdles at
| play. I have worked on dossiers that took 200 man-years at 400k
| per person. This is the development part of pharma R&D. The
| dossier might be a thousand pages submitted, but that can easily
| be 100,000+ pages on the backend.
|
| There's a reason that even billion dollar companies crumble and
| fail under the documentation complexity.
| anthk wrote:
| You will always need peer review, health safety, some insurance
| in case of serious damages and so on.
| magic_smoke_ee wrote:
| If federal funds are used to develop a medication or vaccine, it
| must not be patentable, otherwise it is a corporate welfare
| giveaway trading lives and poverty for money.
| downrightmike wrote:
| But that is 100% the Pharma industry. How did we get an Ebola
| vaccine? USA spent $100M. And they were the only ones willing
| to despite <1% of cases
| Jabbs wrote:
| Looking for a "drug" is part of the problem.
| hooverd wrote:
| Prevention is worth more than cure, sure, but cancer doesn't
| discriminate like that. You can still get unlucky.
| chelseak6 wrote:
| I think it's not possible without needed legislativy
| bastloing wrote:
| AI will change everything. Especially disrupting pharma,
| Hollywood, law and lawyers, and medicine. Only question right now
| is who will win the race and be authoritative?
___________________________________________________________________
(page generated 2024-11-28 23:01 UTC)