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.
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.
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 ).
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.
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.
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.
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.
> 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.
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.
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.
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
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.
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.
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.
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.
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).
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.
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’.
The €30k to €35k 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.
> 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.
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.
> 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.
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.
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".
>Drawing up such a dossier is a profession in itself. An important detail: the EMA is asking for around €350,000 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.
> 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.
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
> 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"
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.
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.
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.
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.)
> 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.
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.
> 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.
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.
Medical trials to prove its safety in human subjects -- pretty essential -- is a lengthy, multi-stage process that is extremely expensive to carry out.
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.
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.
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.
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.
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.
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 ).
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.
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.
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.
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.
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.
> 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.
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.
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.
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
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.
The article literally says "Funded by Bristol Myers Squibb and others".
Supported by Bristol Myers Squibb;
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?
https://www.nejm.org/doi/full/10.1056/NEJMoa2402604
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.
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.
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...
> 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.
Lovely: so just give tons of people an experimental drug and collect garbage data by doing so!
I'm not sure people fully understand the scientific method.
All data is not reliable data.
Discovery is just the tip of the iceberg
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.
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’.
The €30k to €35k 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.
> 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.
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.
> 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...
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.
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".
Translated, unpaywalled:
https://www-ftm-nl.translate.goog/artikelen/ruzie-tussen-zie...
>Drawing up such a dossier is a profession in itself. An important detail: the EMA is asking for around €350,000 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.
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
https://aacrjournals.org/clincancerres/article/22/15/3782/79...
As an aside, what makes this a vaccine vs a treatment?
> 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.
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
> 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/22/15/3782/79...
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.
You will always need peer review, health safety, some insurance in case of serious damages and so on.
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.
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.)
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.
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
> 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.
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.
> 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.
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/S221323172...
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.
Medical trials to prove its safety in human subjects -- pretty essential -- is a lengthy, multi-stage process that is extremely expensive to carry out.
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.
Bullets can induce cell death in a wide variety of cancers as well.
https://xkcd.com/1217/
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.
Rare diseases fund research through philanthropy. And let's not forget Biden's Cancer Moonshot program!
https://www.whitehouse.gov/cancermoonshot/
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.
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.
It happens already. You just have to find the docs who do it. Which usually means attending conferences which focus on specific diseases.
You mean the sort of conferences that attract charlatans and conspiracy theorists?