I am perfectly aware that this is the reason they blame for the insane costs - “we have to test so many drugs!”

Yet you seem to have assumed I’m oblivious to the reality when I’ve already pressed I’ve been in the deep end and am aware.

I’ve already given an explanation on why I don’t agree with “its still serendipitous and random” - the people working on it are not smart enough and are more interested in stoking egos and careers than doing real science, even if they’re capable of doing so.

“90% of the drugs fail in phase I” - why are you telling me that when I’ve already given an explanation on why that is so - we don’t have good preclinical models that correlate with drug effectiveness - is it that you didn’t understand what I wrote, or are also neck deep in this cultural quagmire you refuse to acknowledge it?

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.

All of these things also apply to startups. And creates a VC groupthink of "portfolio theory" that necessitates huge (10,000x) returns, which costs the public a lot of viable small/medium enterprises that are not victims of the perverse incentives.

I wonder if the "optimal" theory is portfolio in this case, or if there is a new generation of VC/pharma investors who want a higher probability at a lower return.

> It doesn’t (have to) cost billions to bring a (successful) drug to market

> you’d be ignoring the costs of the 90% of drugs that fail in phase 1

It depends on what you call "bringing a drug to market".

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* Phase I costs little, around $1M during the trial, and involves only a small group of participants (one or two dozen people), so it's not multi-center and it is manageable by a few people at a biotech. The problem is that most phase I trials fail, but this is not an issue of cost, it's an issue of the way it is decided as explained by ramraj07, another commenter.

Too often it is started on a hunch without solid pre-clinical data, sometimes it is because the drug was tested and failed in another disease and the managers "pivoted" to a new disease because then it costs little to try again, sometimes it's just a "weird IP/financial trick" where you combine an existing drug and an unrelated drug. Then you know you have a relatively efficacious drug, no need for toxicity studies and you can patent it.

On the contrary, many trials could be done on drugs with good pre-clinical data, but that does not happen because it would be hard to patent.

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* A phase III costs around $25M for one or two hundred participants during the trial [0]. It lasts 6 months at most.

Some publications cite much higher numbers (~$1G), but this does not make sense as drugs are often developed by biotechs (startups, in other words) with only a few million in their pockets.

Another cost inflationary cause is subcontracting to CROs, as most biotechs do not have the manpower, knowledge and business connections to conduct the trial.

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* Once a drug receives commercialization authorization, a major company usually buys the rights and then starts the marketing phase. This starts with teaching doctors on how to prescribe and administer the drug. It means publishing articles in the mainstream medical press, inviting doctors to conferences and workshops, and paying medical sales representatives.

It is costly, this is probably where are spend the ~$500M but for me, this is not drug development costs, it's just marketing costs.

[0] http://idei.fr/sites/default/files/medias/doc/conf/pha/conf_...

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.

It’s ironic that you brought Alzheimer’s as an example since it exactly proves your point - drug companies pushed a therapy that targets a highly questionable _symptom_ of the disease, even though every single step of the process gave negative or inconclusive results. It was all about ego and desperate attempts to make profits using iffy drug candidates.

And “biology is complex” is the type of truism I hinted at. You can always say that whenever you fail. Biology is complex and Alzheimer’s is the most complex of them all, to be sure, but I hope you’re aware of the. Alzheimer’s cabal allegations that the entire field was mutilated by a bunch of people into believing and pursuing the wrong hypotheses for decades.

We also don't understand how some drugs work, either (e.g. Tylenol).

Well to be fair, big pharma doesn't release preclinical results the same way that academia does. There might be no published work to support the hypothesis, but that doesn't mean they haven't done preclinical work.

How good are our animal models of ALS? Are they predictive of effectiveness in humans?

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.

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.

I don't know of any hospital pharmacy that has a full fledge biochemistry lab and production facility.

Drug production is very different from the typical work done in a hospital pharmacy.

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.

So the perfect nothing is allowed to block the imperfect something, because we wait for humans to transcend to angelic beeings?

I'm not sure people fully understand the scientific method.

All data is not reliable data.

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.

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".

https://247wallst.com/media/2024/08/04/9-biggest-video-game-...

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.

> 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...

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.

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.

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.

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.

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?)

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.

The only thing you should take away from the stuff RFK says about vaccines is that RFK is a complete kook.

Please explain to us all why glory and survival aren't more effective motivators than the money to be made from patenting something.

What do you think is correct instead?

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.

Hey.

Sorry about your diagnosis.

Thanks for sharing. This is an interesting, though somewhat disappointing, paper.

One thing I didn't get while reading it was the specific blood concentration achieved. I noticed they mentioned 12 rounds with 3 infusion days and 1.5g/kg. I'm assuming they injected that amount daily.

I noticed they injected over a period of 3 hours. To my knowledge the half life of vitamin c in blood is only 2 hours. I wonder if the concentration of vitamin c ever got sufficiently high to induce apoptosis.

At IV clinics near me they offer 75g bags of vitamin c on the website that are administered over an hour. I bet you could go back to back and get a higher concentration. In the same trip I wonder if you could get something fun - an IV clinic near me offers a nootropic, methylene blue, might charge you up for a day of studying cancer treatments.

One final idea I've had, not sure how useful it is to you, is that you can an at home ultrasound for a few thousand dollars. You should be able to use it to see your intestines and the tumors growing inside. You could use this to monitor your own treatment - i.e. take daily pictures and examine before and after vitamin c therapy, to see if it does anything.

Best of luck to you. If you want to bounce ideas for DIY cancer treatments off of anyone let me know and we can exchange emails.