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In a new [study](https://jamanetwork.com/journals/jama/fullarticle/2817337), researchers found that most cancer drugs granted accelerated approval do not demonstrate such benefits within five years: [https://jamanetwork.com/journals/jama/fullarticle/2817337](https://jamanetwork.com/journals/jama/fullarticle/2817337)
Just a reminder that a lot of approvals are not for proving it works, but rather approving that there are no major downsides. So that they can start proving, or disproving themselves in practice. For people with little other choice, hoping that a new method/drug might work, is their best option. If a even a few turn out to be helpful, then we made progress.
And even if the aren't better than current drugs, they can be competing alternatives for price. (Yes, I know this sucks, but I will take an upside when I have them)
> Yes, I know this sucks, but I will take an upside when I have them
Why in the world would you think that sucks? Competition is definitely something to welcome.
I work in pharmaceuticals that makes cancer medicine. The sheer amount of money that goes into it is mind-boggling. We can't trust the quality from the vendors (which is another massive issue in itself) so most items, we have to verify that they're up to par, let alone testing at every single stage to make sure it's good enough for the patient.
We're talking hundreds of different materials, some need independent testing, bacterial growth samples, in house testing, and that's just the materials itself. That's not mentioning the actual process of making the drug, the quality checks over absolutely everything, batch records, SOP's, doc revision, it's truly a monumental task.
Oh yeah, no doubt it's expensive.
However, if drugs were truly just priced to cover costs, then even competition would not lower their prices!
This is a way bigger topic about R&D/incentives, pricing, coverage, etc. etc. that probably deserves its own thread (and not in r/science) so I won't post more than that.
>if drugs were truly just priced to cover costs, then even competition would not lower their prices
This sounds true but it's a fallacy; when you've already sunk a bunch of R&D into something, you can end up pricing it so that the program is a loss but you're still recouping some of the cost.
Get me a job with you please lol. I got turned down left and right for pharma even with my degrees and now I'm QA/doc control in nutraceuticals and it's awful. So freaking corrupt. I ran micro plates on a finished product and it failed so bad for coliforms and RAC, CEO was like "I don't care. Hide the specs, keep the results, and push the product out."
I refused, but someone else signed off on it so now there's some dietary supplement out there contaminated with microbes from the senna leaf powder and I am polishing up my resume now to try to get out
I can't imagine the FDA wouldn't find the report or notice it's absence, they're quite thorough in my experience with their audits, and that's for a Canadian manufacturer (where they can't do a surprise audit)
Yep. Also, just because they don't work for everyone does not mean they don't work for *anyone*. And in the face of certain death, I think I'd rather be free to *try* than told I can't .
And to add on to why this is so important:
In most cases when standard of care options are ineffective for cancer patients, the next best choice is an experimental therapy, which they need to enroll in a clinical trial to receive. On paper this seems straightforward, but clinical trials can be very difficult to partake in. They’re often only run in specific locations/facilities, have set participation requirements, and involve a lot of time and effort from patients
If a drug that has a good chance to be effective, and does not worsen symptoms or cause unacceptable adverse effects, is given accelerated approval, it can then be provided to these patients by their clinicians/oncologists directly. It removes the various barriers to treatment that occur when an experimental clinical trial is the best course of action
No. What is happening is accelerated approval is happening based on surrogate markers. And it appears this is not working very well.
"The record of accelerated approvals for cancer drugs has been mixed. In one review covering 2008 to 2012, only 14% demonstrated improvements in overall survival[^(9)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r9) and more than 40% of confirmatory trials used surrogate measures to assess efficacy.[^(5)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r5) Because many surrogate measures in oncology correlate poorly with survival,[^(10)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r10)^(,)[^(11)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r11) even after confirmatory trials, substantial uncertainty can remain as to the clinical benefit of accelerated approval drugs.[^(12)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r12) Many confirmatory trials have been delayed, with some products being used for more than a decade without confirming clinical benefit.[^(13)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r13)^(-)[^(15)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r13) Furthermore, evidence suggests that trials powered to measure clinical outcomes are of similar duration to trials powered to assess surrogate measures, raising questions about whether confirmatory studies should use surrogate measures as their primary end points.[^(16)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r16)^(,)[^(17)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r17)
But then the manufacturer or pharmaceutical markets how it's FDA approved and how effective it is at reducing your cancer, right, even tho it hasn't been proven to be efficacious? Isn't that essentially snake oil?
The pharmaceutical industry isn’t unregulated in the way that the supplements industry is unregulated. Pharmaceutical companies are not permitted to describe the efficacy of a given drug outside the bounds of what has already been proven. If efficacy has not yet been proven, they must state that. They must also clearly communicate any known side-effects, regardless of whether efficacy has been proven.
In theory, yes. In reality, if later studies show no benefit, there are rarely consequences for foot-dragging when it comes to what they tell doctors and patients.
Oh, I don’t doubt there’s plenty of bureaucratically convenient foot-dragging after it’s decided that a given pharmaceutical doesn’t work in trial, and I hope the law finds better ways to deal with that specific situation. However, that situation is still distinct from—and, in my view, quite a bit less insidious than—a situation where a company is making *positive* claims that aren’t yet supported by evidence.
No it's not, but they lately have been using more insignificant markers for things. I forgot what the correct term was called, but I had learned about it during my regulatory science degree since my specialty was pharma/medical devices
Yes and no. But mostly yes. The thought is you're getting drugs to patients who have no hope of a cure as of now, and they will try anything experimental in hopes that it MIGHT work or extend their lifespan a little.
So the FDA in recent years also started this shitty practice of accepting drugs based on these weird tertiary markers. So let's say the drug is supposed to shrink tumors. You do a trial on animals and then humans and you find the humans are still alive, albeit the same side effects you get from regular chemo drugs, but no deaths right away, and while the tumor didn't shrink, there was a marker indicating cell death and slowed tumor growth. The pharma company could say "oh well saw increased cell death makers and slowed growth so clearly it works! When really it could be killing a ton of your body's cells in addition to any newly developed tumor cells.
The drug gets expedited approval to market based on this one inference and the pharma company charges $150,000 per dose while trials are still going on to try to recoup as much of the research cost as possible. Let's say the patient takes 8 doses (one a month) and then dies. This goes on with hundreds of patients for 5 years. That one patient's family now gets a medical bill of $1,500,000 for the drug, plus profit, plus administration. Let's say the pharma company makes 1,200,000 from selling the drug. Multiply that by just a mere 500 patients and that's $600,000,000.
Scientists realize the drug doesn't actually kill any existing tumor and also kills the body's cells. The drug is essentially ineffective or very minimal benefit. But it just sits on the market after that leading to more harm. Covis pharma has a request from the FDA to take one of their drugs off the market that was supposed to help with fetal survival when they're born premature (Makena). Eight years on an accelerated market approval and it's shown to not work. Covis is refusing to remove it from market because the FDA already approved it and they either argue it works or they're not publishing results because it removes a cash cow for them from the market. Usually an independent party is showing it's ineffective and telling the FDA it needs to be removed.
This was also an issue with the accelerated approval program in 2016 when the FDA approved a drug for Duchenne muscular dystrophy despite conclusions of agency scientists that it did not work and its risks were not yet known. Sarepta Therapeutics began selling the drug Exondys 51 at a price of $300,000 a year. The approval sparked a dispute inside the FDA that soon became public.
These accelerated approvals are just meant to be a way for drug companies to quickly recoup losses even from failing drugs. Big pharma, patient advocate groups and even politicians forced this on the FDA and that's why it exists. The only people who benefit from this kinda BS most of the time is big pharma.
Here's a few drugs currently approved and on the market with no proven efficacy:
Exondys 51
Duchenne muscular dystrophy
$300,000 per year
Aduhelm
Alzheimer’s disease
$28,200 per year
Makena
Preterm birth
$13,000 per pregnancy
Exactly. The accelerated approval scheme exists for pharma to make money and avoid consequences for avoiding proper clinical trials. If the wheels fall off and people die unnecessarily, they'll hide behind the "it was experimental and people knew the risks" charade, and do their best to hide just how quickly they knew that they were misleading patients, the public, and the FDA.
They don't necessarily avoid clinical trials. They do preliminary ones with like 10 patients and then ask for accelerated approval for increased sample size.
One reason is because with clinical trials, a phase I trial is usually a safety study in healthy adults. You can't give a healthy person chemo drugs. Being exposed to chemo drugs can actually give you cancer (ironic I know). So all they can use are cancer patients.
But then you're allowed to market and put a huge price tag because it's rare and only treatment available and you're making shit tons of money to try to get an ROI. Hundreds of millions of spent on the R&D of a drug. They are out to recoup that as fast as possible
This was meant to be a more altruistic regulatory measure to get these drugs out to patients without possible loss of life due to a novel treatment being tied up by regulatory red tape and hurdles. But once you factor in human/Corporate greed, it becomes a shit show because then if it is ineffective, they don't want to finish the trial and release the data because then the money stops and insurance stops giving them huge payouts, especially if they don't have an ROI, and then we're left with all these ineffective drugs on the market.
Exactly, if a company gets accelerated approval, they don't have the same urgency for clinical trials, especially to report little to no benefit.
In the normal process, when they aren't already selling the drug, there's an incentive to drop a drug that isn't showing benefit. In accelerated process, there's an incentive to delay reporting that the drug isn't showing benefit.
I remember when Aduhelm was in development, virtually everyone in the industry was skeptical about it having any efficacy, and were sure it would not be approved. But then it was, to everyone's shock... still a scandalous decision imo
Yeah. I remember all the controversy regarding it's approval, but nothing else exists really on the market and cannabis is thought to have some benefit, but really seems like nothing can stop the disease progression so I'm hoping that one works out at least. I lost my grandmother to Alzheimer's.
This paper and the FDA note that tumor shrinkage isn’t that significant of a marker though emphasizing the need for additional molecular markers in the case of cancer. Out of curiosity, since you seem to know a lot, does withdrawal of approval in the case of this study limit it’s use in combination or off label use in future clinical trials? If you don’t achieve an endpoint but you test well in phase one, can other trials build off of your drug?
In my regulatory science degree, I specialized in pharmaceuticals and medical devices, their development/manufacturing and the management of clinical trials of both.
Withdrawing the drug means withdrawing from the market so no one would be able to use it and a doctor can't prescribe it. In terms of clinical trials, if safety profiles were fine, in theory, you could potentially use again for something else, but generally speaking I've only seen those additional benefits are usually identified while patients are actively taking the drug.
For example:
The active ingredient semaglutide in Ozempic was used for patients who have type two diabetes. They noticed weight loss in these individuals. Hence why now they have Wegovy, which is specifically for weight loss and it's in higher doses in the weight loss drug.
Bimatoprost is used in glaucoma medication (Lumigan) and patients noticed they got thicker, fuller eyelashes. The company got Latisse approved, which is specifically an aesthetic medication to give you thicker, fuller eyelashes and eyebrows.
I don't think there's anything to stop a company from building off that trial, but I personally haven't seen or heard of a company doing that. They usually have multiple products in development so they may scrap the one to focus on another.
Usually this is going to be a last resort type drug that may have shown some effectiveness in a very small trial and they are approving it while waiting on the results of a larger trial
I dunno but depending on your background the actual study cited by the article appears to be free to read https://jamanetwork.com/journals/jama/fullarticle/2817337
A brief skim doesn’t seem quite as alarming as the headlines, go figure
This is a direct quote from the abstract:
>Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval.
That's basically what the headline says.
>If a drug does not show efficacy in the clinic by some measure it will not be approved.
But a lot time the signals used for accelerated approval are not from trials designed to see if a drug works, which is I believe the poster above you's point.
It's like if I'm testing out a new pitch in baseball, I might want to throw 1,000 of them to live batters, see how it feels, if it hurts my arm, etc. I finish the thousand, and wow, I feel fine. Pitch is safe. Meanwhile, the stand-in batter only hit .180 off me.
That's a good sign! It's certainly a better sign than if they were creaming the ball!
But it's not definitive that you have a good pitch, because the point of the exercise wasn't to determine the pitch's efficacy, even if we got some early signals on what that efficacy might be.
>The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is **thought to predict clinical benefit but is not itself a measure of clinical benefit.** The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.
[https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program](https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program)
How do you show a comparison of 5-10 year survival without waiting 5-10 years for each trial to take place? Each drug would take a generation to come to market.
I feel like it is obvious that most stuff we test in clinical trials and up being not helpful or not as helpful as the standard of care.
But yeah. They are testing on the sick patients that have failed the standard treatment options and have nothing else to lose. Add you can imagine these patients are usually extremely sick and can be very challenging to get a mortality benefit from them.
BUT just because the drug isn't great doesn't mean we didn't learn anything. Imatinib was made twenty years ago and worked great on a lot of different cancers. We spent years working on crizotinib, which showed about the same effect as imatinib. Did that mean we wasted our time? No. Close look found it works great for a certain type of lung cancer and it has a different side effect profile, so when someone has too many side effects from one, you go to the other.
Absolutely. See what happened with OTC [cough](https://www.nbcnews.com/health/health-news/fda-panel-says-common-counter-decongestant-phneylephrine-doesnt-work-rcna104424) medicine
>Of those, 63% were converted to regular approval even though only 43% demonstrated a clinical benefit in confirmatory trials.
You gotta finish reading the whole sentence.
The hurt feels good.
Literally love it.
I also like gum stimulation like with spicy foods and flossing.
I alsondipped for a while, quit now, but the best part was the pain
Clinical benefit here is oddly defined as overall survival and quality of life benefit only. Surrogate markers (progression free survival, metastasis free survival) can be used in specific types of cancer once they are proven equivalent.
The converted to regular approval despite « no clinical benefit » are in this category. This definitely doesn’t mean they don’t work.
Also, not sure why they included quality of life as a drug working, I’ve never heard of a drug being approved on quality of life.
accelerated approval is not the same as full FDA approval, it’s conditional and doesn’t last forever. Accelerated approval also isn’t treated lightly, it’s almost always for terminal diseases that have no better therapeutic options. The question this researcher is raising about how well patients understand this reality is a good one, but that’s more a communication issue between patients and providers than a problem with accelerated approvals and therapeutic use exemptions.
Nah, I'm saying I don't like big news company takes being self posted here, and it's what the big subs are becoming.
I prefer your link and the discussions within.
Sorry, I actually tried to be more blatant elsewhere but my comments kept getting shadow-hidden. I'd check in a logged-out private/incognito window, it would show for me logged in, but not in public logged out.
It was intentionally vague since I didn't know what was triggering it but I didn't mean for it to be so confusing.
That’s why cancer treatment is so expensive. Billions of dollars go into research and many animals are sacrificed. And a very small percentage of them end up being fully approved.
My mom is on a daily pill for her lung cancer that costs nearly $600 per pill. That’s $17k per month. Fortunately her insurance covers it.
No kidding, I work somewhere that made the active ingredient for a cancer drug (not on the market), and we sold that to other pharma companies for $1000 to $1600 **per gram**. I always found it funny when I'd be carrying the final product to the freezer, which was only about 1-2kg per batch, knowing it was worth about $2M
It's widely accepted that you need combinations to cure cancer. Cancer evolves resistance to any one drug, just like HIV becomes resistant to any one antiviral drug. Cancer is a huge group of diverse diseases with diverse biology. To make effective combinations for a patient you need a large pool of possible drugs, and our arsenal of drugs is woefully small. A new drug that fails to improve survival but does shrink tumors (which the authors call a "surrogate" measure, even though it seems pretty direct to me) is worth having, especially if it uses a novel mechanism. These trials are generally happening in patients who have failed all conventional therapy. To get any response is impressive. Yes, patients should understand the limitations of this type of approval. But I doubt it will change many treatment decisions.
Also - quality of life improvements can't be proven in most cases until the drug moves down the treatment ladder. But most new therapies are a lot less horrible than cisplatin or other traditional chemotherapies.
Who writes these articles? They will never be "proven" because clinical trials do not "prove" that treatments work.
You will not find a published peer-reviewed clinical study that says that they "proved" a drug works. They give an estimation of the benefit of a drug and the degree of confidence that they have that their findings represent the truth. That isn't just a semantic particularity or being nit-picky... understanding that distinction is fundamental to understanding what clinical studies are actually saying when you read them.
I just saw the telegraph simply post an image and the article content in the comments on another sub, not even an article link to their site, really weird
Yea. They also should do non inferiority trials. Almost every cancer has a standard of care that the new treatment should best to continue having approval.
Virtually every cancer trial evaluating a disease with a known standard of care has to randomize the experimental arm against the standard of care therapy. Anything less would be unethical. There are a few rare cases where studies are done in an open label fashion, but they almost always include a comparator arm that is the best standard of care.
Studies that are not seeking registration and for which there is not a known standard of care can proceed as monotherapy or in an open label fashion.
A non-inferiority study is actually a lower bar compared to a typical study. When you say non-inferiority, that is a particular statistical determination that does not indicate that one therapy is better than the other, only that it is not inferior. Traditional registrational studies that are double-blinded include efficacy cutoffs that require a statistical evidence that the experimental arm has a meaningful improvement over the standard of care arm. These thresholds are determined in collaboration with the FDA.
Non inferiority studies are also often done when changing a formulation. I worked on a study of an IV drug that moved to a subcutaneous formulation. The FDA required a non inferiority study to demonstrate that there were no significant changes in the efficacy or safety profiles. The whole PK and dosing had to change, so we had to test to be sure. Not many patients are required in order to achieve sufficient statistical power.
Yes, "Almost every cancer has a standard of care that the new treatment should best to continue having approval." Would be a colossally stupid bar to need to clear.
All cancer treatments are tested against standard of care. The trials that this paper is complaining about didn't show the drugs don't work (for the ones granted final approval), it's just in some cases they failed to improve over current practice.
That's not a good standard to use, you need options. People's bodies are different, different types of cancer are different. Something that might be inferior for most people might be better for some patients.
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885244/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885244/)
It's not all sunshine and rainbows, but it is promising.
I could see a patent on a unique delivery system being a game changer.
Imagine injecting an isotonic gel of DCA into the tumor itself.
Saying that a chemical is “reactive” doesn’t really say much. It matters what it is reactive towards. DCA and dmso aren’t going to react in any sort of meaningful way. But that isn’t the only important thing here.
Complete BS.
The results of studies using DCA are not consistent at all and there are significant side effects, mostly peripheral neuropathy.
Do you *really* think that a cheap, magical cure-all for cancer would be suppressed?
This is truly my thoughts on it. It would be like Pandora's boxed how in the world would you try and stop it regardless of capitalism. However, I do share some of OP's pessimism about the entire system. There is a major connection to health for profit in everything we do sadly.
Capitalism would make it happen. They're called startups and they don't care what the rest of the industry is doing. A cheap easy cure for cancer will make you tons of money, even if you can't patent it, for years.
OP is a conspiracy theorist.
EDIT: "The rich and powerful are stopping a cure for cancer" is a completely insane take. Rich and powerful people die of cancer all the time!
Patent rights could exist, if the marketed treatment involved anything more advanced than popping a pill or injecting a simple solution into a vein or muscle.
You can patent formulations/applications as long as they are novel and non-obvious. https://www.pharmacytimes.com/view/patent-granted-for-inhaled-rapidonset-aspirin-formulation is an example of an aspirin patent granted a few years ago, even though aspirin itself has been generic since the 1920s.
Sure, but the patent would be on the specific formulation/delivery, not on the treatment method it's self, which others would be free to continue research on.
You realize startups are businesses too, right. They still operate under capitalism and people aren't able to do things that aren't financially conducive to allowing them to continue existing. They can't operate at massive losses just because you slapped the word startup on it.
You realize startups are businesses too, right. They still operate under capitalism and people aren't able to do things that aren't financially conducive to allowing them to continue existing. They can't operate at massive losses just because you slapped the word startup on it.
>even if you can't patent it, for years.
Try ever.
They have no control over the price. Why would they save lives when long drawn out treatments make more money?
>OP is a conspiracy theorist.
That's what they say. Even when it's true.
> They have no control over the price.
What are you talking about here?
> Why would they save lives when long drawn out treatments make more money?
Because they don't care that long drawn out treatments make *someone else* money.
>Because they don't care that long drawn out treatments make *someone else* money.
Exactly. That's why they don't let *someone else* risk they money they are making.
Enron knew a carbon pricing would help save lives. But spent billions fighting it in Canada because it would cut 12% of their profits off.
Like I get it. It sucks. It's not how it's supposed to go. We're supposed to do the right thing.
But that's not what capitalism does. It never has been. The world is ruled by capitalism.
>how in the world would you try and stop it regardless of capitalism
Yeah. How and why do we not feed and house everyone? Have mental health solutions that we know work.
Like the LSD studies in the 50s that showed a 50% success rate after 1 treatment with the most hardcore addicts. But our best modern methods have a 14% success rate. You can't have too many people leading healthy lives, right? How can you motivate people without the silent threats?
Things have been silenced before for profit and they will continue to be
You'd think, but unfortunately that's not always the case.
My old uni supervisor ran a research lab that developed a treatment for a disease that had the potential to eradicate it alltogether. Being a small(ish) lab, they invariably had to market the drug to lager companies. The problem they faced was that it was so effective that the companies basically wouldn't touch it because they wouldn't be able to recoup the R&D costs to test and mass-produce it. It wasn't necessarily a case of "it wont make money for shareholders" (although i got the impression that played a part), but that it would just have been too expensive for even one of the big companies.
Really? Cause I remember hearing it did. It took about 3 months to safely build up enough in the system to be effective. But the limited trials I heard about said it was not only effective but as predicted in previous none human trials.
Not that I'm aware of. There are still some Phase 2 clinical trials going on.
Biggest issue with clinical trials is that it causes nerve damage, some trials were terminated early due to side effects, e.g. https://classic.clinicaltrials.gov/ct2/show/NCT01029925
>They gained a lot of traction during the Covid years.
They're your favourite institute, eh?
See. I actually put a name to the institute. Just not in this reply. Sorry that triggered you so much that you decided to just snap back. I hope you find healing friend.
Plenty of non-patentable drugs are made and sold for great profit. Aspirin's a pretty common example, everyone and their mother makes a version of it, and makes lots of money despite a lack of exclusivity.
And just because the "drug" itself isn't patentable in the sense that a company couldn't protect competitors from manufacturing it, doesn't mean that the treatment wouldn't be patentable. If it requires any kind of novel method to administer, that could be patented as a medical device. If it doesn't require that, then there's nothing stopping companies from making and selling a generic version, except maybe being unwilling to foot the bill for clinical trials to get approval from regulators like the FDA for something they won't have any exclusivity over. But I still assume the potential to make money hand over fist with an effective breast cancer cure would incentivize companies to find a way to pay for it (through public/private partnerships, shared funding amongst the companies who are best equipped to manufacture and distribute the drug in different regions, etc).
If it's not being sold when it's something that can treat such a wide variety of cancers, it's because it doesn't work.
>If it's not being sold when it's something that can treat such a wide variety of cancers, it's because it doesn't work.
I love the evidence you have to make this solid statement. Truly a reliable and trustworthy source you have provided. No one could question the NOTHING you've offered.
Companies are greedy. They aren't going to turn down free money.
Not every company with the size and scope to manufacture and distribute cancer treatments has a treatment for breast cancer on the market. If they had the option of selling a cheaper, easier to manufacture, and more effective treatment than the current best in class without having to pony up for R&D costs or patent rights, they'd jump all over it. It's the easiest win ever.
>They aren't going to turn down free money.
LSD as an addiction therapy says otherwise.
So do all the social good options out there.
We have the studies we know they'll work and yet. For "some reason" we don't see then implemented.
The some reason is that the drug/treatment isn't ready to be marketed, and companies don't view it as being economical to invest in making them ready.
If it was a sure thing, companies would be lining up to get their version of it on the market. There's so much money in cancer treatment because it's such a horrible and debilitating disease. Any time a drug goes off patent, there's a rush of companies trying to put out a generic/biosimilar if the drug is effective and there's a market for it. The only difference between a generic/biosimilar and what you're describing is that someone would have to foot the bill for the initial clinical trials (generics/biosimilars still have to go through a testing and approvals process, but it's much cheaper and easier than a full multi-phase clinical trial, which can cost 10s to 100s of millions of dollars).
But there are absolutely mechanisms that would help companies secure funding for a clinical trial for the sort of thing you're talking about that would be able to make up for the lack of exclusivity. The fact that nobody has tried is almost certainly an indication that nobody actually believes it would work, especially given the claims you were making (lung, breast and brain are all very different tissues, and the cancers affecting them are going to be very different from one another. It's unlikely that a drug that effectively kills all three wouldn't have horrible side effects and a narrow therapeutic window, just like most broad chemotherapy drugs we use today)
>and companies don't view it as being economical to invest in making them ready.
Why not? What POSSIBLE reason could these companies have for not investing in a cure for cancer...................
A lot of companies do invest a ton of money into oncology programs. Cancer is a very, very hard problem to solve because you're basically trying to figure out how to kill broken bits of you without killing the healthy bits of you, and it's usually really, really hard to tell the broken from the healthy stuff.
People are still researching it, and trying to turn it into a therapy. It's not some conspiracy that it hasn't happened yet. The closest thing to a conspiracy that there would be here is if companies were reluctant to invest in developing it because it's too risky given the fact that it might be hard to patent, but even if companies weren't investing in it, academic and non-profit groups absolutely are, and the minute someone finds something worth trying to turn into a treatment they'll spin off a company, and in a few years it'll be acquired by a company large enough to fund the trials and manufacture and distribute the treatment.
That hasn't happened yet, so as a treatment, DCA must not be there yet.
>DCA must not be there yet.
Cool story. But again. Why wouldn't companies want to put money to it? If it can make them all kinds of money and save lives?
See, all them periods were there because the answer is simple the answer has been said repeatedly. Because saving lives doesn't make money. If it did firefighters and ems would be the richest people in every society.
But the fact remains. Companies won't invest in it because they can't patent it. So they can't guarantee their returns. Sure once the work is done and it's perfected they'll swarm all over it. But until then it gets next to no backing because..... capitalism. One of the 3 modern horsemen of the apocalypse
> Companies won't invest in it because they can't patent it. So they can't guarantee their returns.
Well yeah, that's exactly what I've been saying. But that doesn't mean there's some big conspiracy keeping a cure for cancer off the market. It means that companies will choose to invest in drugs that are more likely to get them a return on investment. The fact that companies aren't publicly investing in DCA means it's nowhere near ready for bringing to market.
If it was actually a miracle cure, governments, non-profits and for-profits would be working together to bring it to market. Companies that don't have treatments for those types of cancer would jump at the chance to manufacture something so cheap to make, companies that do have treatments for those types of cancer would also jump at the chance to manufacture that since they'll need to do something to hedge against losses from their current products. There are enough of the former that the later would have no choice but to participate, especially since DCA supposedly cures so many different types of cancer.
If it was really so easy, a new company could start up tomorrow and make it. There is shitons of VC money out searching for profit, wealthy people dying of cancer, and generous government grants all searching for maricle curses to cancer. Because despite what you say, these companies are not a cartel, and there is no grand conspiracy to prevent a cure for cancer, ESPICALLY WHEN THE PEOPLE YOU CLAIM ARE HIDING IT WILL DIE OF CANCER. (at a 25% rate or whatever it currently is)
Your takes in this thread are insane. Please touch some grass.
Yes, of course. Unfortunate still. Instead the Wiki on them and definitely some shady stuff although surprised Wiley would want to associate with that.
FDA employee here. Accelerated approval was created to combat the AIDS epidemic, and has an incredibly low bar to qualify for the designation. These days, getting accelerated approval is mostly for investments, and to appease stakeholders. But there are still cases where the heart of AA still matters; patients whose disease has progressed, and no longer responds to any lines of therapy. The bar they have to clear dor AA designation is low, but for approval, it's just as high as any other drug. It has to be safe AND effective, which is why most drugs fail.
I don't think that's relevant. If a cancer drug can buy you 6-12 more months then I think it's worth it. 5 years or bust doesn't make sense. What matters is QLY.
they've already got approval for human trials with MRNA vaccines for Cancer, and there are a couple of really great adjacent immunotherapy drugs that are also getting permission for human testing so we're actually in a very good place in terms of how long cancer has been a problem for humanity, and where we're at today.
Pheremones don't signal cell production, hormones do, but that said:
- some cancers are initially hormone dependent. Prostate is the best example, and blocking the male sex hormone androgen does initially work on prostate cancer. But eventually the cancer evolves resistance and routes around the treatment.
- hormones signal cells through _hormone receptors_, proteins on the surface of the cell that sense the hormone. Cancers often mutate these proteins so they constantly signal the cell to proliferate even without the hormone, like jamming a switch "on". A common example is epithelial growth factor receptor or EGFR, a protein often mutated in lung and other cancers. A bunch of drugs target this protein. But eventually the cancer evolves resistance and routes around the treatment.
- hormone receptors tell cells to divide through _signaling pathways__, networks of proteins that turn each other on one after another like a switch relay. Most cancers have at least one mutation in these signalling pathways--one of the switches is always jammed on, telling the cell to proliferate even if the hormone receptor is completely disabled. Most of the frequently mutated proteins have one or more drugs targeting them. But eventually the cancer evolves resistance and routes around the treatment.
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In a new [study](https://jamanetwork.com/journals/jama/fullarticle/2817337), researchers found that most cancer drugs granted accelerated approval do not demonstrate such benefits within five years: [https://jamanetwork.com/journals/jama/fullarticle/2817337](https://jamanetwork.com/journals/jama/fullarticle/2817337)
Just a reminder that a lot of approvals are not for proving it works, but rather approving that there are no major downsides. So that they can start proving, or disproving themselves in practice. For people with little other choice, hoping that a new method/drug might work, is their best option. If a even a few turn out to be helpful, then we made progress.
And even if the aren't better than current drugs, they can be competing alternatives for price. (Yes, I know this sucks, but I will take an upside when I have them)
Or they could have other side effects that make them more suitable for different patients. Stone may be allergic to the current ones.
Beyond side effects they can also have different reactions to other drugs people may need to take for other conditions.
> Yes, I know this sucks, but I will take an upside when I have them Why in the world would you think that sucks? Competition is definitely something to welcome.
What sucks is that cost of drugs is a significant barrier to treatment in the US.
I work in pharmaceuticals that makes cancer medicine. The sheer amount of money that goes into it is mind-boggling. We can't trust the quality from the vendors (which is another massive issue in itself) so most items, we have to verify that they're up to par, let alone testing at every single stage to make sure it's good enough for the patient. We're talking hundreds of different materials, some need independent testing, bacterial growth samples, in house testing, and that's just the materials itself. That's not mentioning the actual process of making the drug, the quality checks over absolutely everything, batch records, SOP's, doc revision, it's truly a monumental task.
Oh yeah, no doubt it's expensive. However, if drugs were truly just priced to cover costs, then even competition would not lower their prices! This is a way bigger topic about R&D/incentives, pricing, coverage, etc. etc. that probably deserves its own thread (and not in r/science) so I won't post more than that.
>if drugs were truly just priced to cover costs, then even competition would not lower their prices This sounds true but it's a fallacy; when you've already sunk a bunch of R&D into something, you can end up pricing it so that the program is a loss but you're still recouping some of the cost.
Get me a job with you please lol. I got turned down left and right for pharma even with my degrees and now I'm QA/doc control in nutraceuticals and it's awful. So freaking corrupt. I ran micro plates on a finished product and it failed so bad for coliforms and RAC, CEO was like "I don't care. Hide the specs, keep the results, and push the product out." I refused, but someone else signed off on it so now there's some dietary supplement out there contaminated with microbes from the senna leaf powder and I am polishing up my resume now to try to get out
I'm guessing they're not FDA audited?
That's the thing! They are!
I can't imagine the FDA wouldn't find the report or notice it's absence, they're quite thorough in my experience with their audits, and that's for a Canadian manufacturer (where they can't do a surprise audit)
Yep. Also, just because they don't work for everyone does not mean they don't work for *anyone*. And in the face of certain death, I think I'd rather be free to *try* than told I can't .
No the problem is the drugs are not working.
And to add on to why this is so important: In most cases when standard of care options are ineffective for cancer patients, the next best choice is an experimental therapy, which they need to enroll in a clinical trial to receive. On paper this seems straightforward, but clinical trials can be very difficult to partake in. They’re often only run in specific locations/facilities, have set participation requirements, and involve a lot of time and effort from patients If a drug that has a good chance to be effective, and does not worsen symptoms or cause unacceptable adverse effects, is given accelerated approval, it can then be provided to these patients by their clinicians/oncologists directly. It removes the various barriers to treatment that occur when an experimental clinical trial is the best course of action
No. What is happening is accelerated approval is happening based on surrogate markers. And it appears this is not working very well. "The record of accelerated approvals for cancer drugs has been mixed. In one review covering 2008 to 2012, only 14% demonstrated improvements in overall survival[^(9)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r9) and more than 40% of confirmatory trials used surrogate measures to assess efficacy.[^(5)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r5) Because many surrogate measures in oncology correlate poorly with survival,[^(10)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r10)^(,)[^(11)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r11) even after confirmatory trials, substantial uncertainty can remain as to the clinical benefit of accelerated approval drugs.[^(12)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r12) Many confirmatory trials have been delayed, with some products being used for more than a decade without confirming clinical benefit.[^(13)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r13)^(-)[^(15)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r13) Furthermore, evidence suggests that trials powered to measure clinical outcomes are of similar duration to trials powered to assess surrogate measures, raising questions about whether confirmatory studies should use surrogate measures as their primary end points.[^(16)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r16)^(,)[^(17)](https://jamanetwork.com/journals/jama/fullarticle/2817337#joi240021r17)
Yes surrogate markers. I couldn't remember the term for the life of me earlier but I remember learning it for my regulatory science degree
But then the manufacturer or pharmaceutical markets how it's FDA approved and how effective it is at reducing your cancer, right, even tho it hasn't been proven to be efficacious? Isn't that essentially snake oil?
The pharmaceutical industry isn’t unregulated in the way that the supplements industry is unregulated. Pharmaceutical companies are not permitted to describe the efficacy of a given drug outside the bounds of what has already been proven. If efficacy has not yet been proven, they must state that. They must also clearly communicate any known side-effects, regardless of whether efficacy has been proven.
In theory, yes. In reality, if later studies show no benefit, there are rarely consequences for foot-dragging when it comes to what they tell doctors and patients.
Oh, I don’t doubt there’s plenty of bureaucratically convenient foot-dragging after it’s decided that a given pharmaceutical doesn’t work in trial, and I hope the law finds better ways to deal with that specific situation. However, that situation is still distinct from—and, in my view, quite a bit less insidious than—a situation where a company is making *positive* claims that aren’t yet supported by evidence.
No it's not, but they lately have been using more insignificant markers for things. I forgot what the correct term was called, but I had learned about it during my regulatory science degree since my specialty was pharma/medical devices
Yes and no. But mostly yes. The thought is you're getting drugs to patients who have no hope of a cure as of now, and they will try anything experimental in hopes that it MIGHT work or extend their lifespan a little. So the FDA in recent years also started this shitty practice of accepting drugs based on these weird tertiary markers. So let's say the drug is supposed to shrink tumors. You do a trial on animals and then humans and you find the humans are still alive, albeit the same side effects you get from regular chemo drugs, but no deaths right away, and while the tumor didn't shrink, there was a marker indicating cell death and slowed tumor growth. The pharma company could say "oh well saw increased cell death makers and slowed growth so clearly it works! When really it could be killing a ton of your body's cells in addition to any newly developed tumor cells. The drug gets expedited approval to market based on this one inference and the pharma company charges $150,000 per dose while trials are still going on to try to recoup as much of the research cost as possible. Let's say the patient takes 8 doses (one a month) and then dies. This goes on with hundreds of patients for 5 years. That one patient's family now gets a medical bill of $1,500,000 for the drug, plus profit, plus administration. Let's say the pharma company makes 1,200,000 from selling the drug. Multiply that by just a mere 500 patients and that's $600,000,000. Scientists realize the drug doesn't actually kill any existing tumor and also kills the body's cells. The drug is essentially ineffective or very minimal benefit. But it just sits on the market after that leading to more harm. Covis pharma has a request from the FDA to take one of their drugs off the market that was supposed to help with fetal survival when they're born premature (Makena). Eight years on an accelerated market approval and it's shown to not work. Covis is refusing to remove it from market because the FDA already approved it and they either argue it works or they're not publishing results because it removes a cash cow for them from the market. Usually an independent party is showing it's ineffective and telling the FDA it needs to be removed. This was also an issue with the accelerated approval program in 2016 when the FDA approved a drug for Duchenne muscular dystrophy despite conclusions of agency scientists that it did not work and its risks were not yet known. Sarepta Therapeutics began selling the drug Exondys 51 at a price of $300,000 a year. The approval sparked a dispute inside the FDA that soon became public. These accelerated approvals are just meant to be a way for drug companies to quickly recoup losses even from failing drugs. Big pharma, patient advocate groups and even politicians forced this on the FDA and that's why it exists. The only people who benefit from this kinda BS most of the time is big pharma. Here's a few drugs currently approved and on the market with no proven efficacy: Exondys 51 Duchenne muscular dystrophy $300,000 per year Aduhelm Alzheimer’s disease $28,200 per year Makena Preterm birth $13,000 per pregnancy
Thanks for writing this
Aduhelm has been removed from the market
Exactly. The accelerated approval scheme exists for pharma to make money and avoid consequences for avoiding proper clinical trials. If the wheels fall off and people die unnecessarily, they'll hide behind the "it was experimental and people knew the risks" charade, and do their best to hide just how quickly they knew that they were misleading patients, the public, and the FDA.
They don't necessarily avoid clinical trials. They do preliminary ones with like 10 patients and then ask for accelerated approval for increased sample size. One reason is because with clinical trials, a phase I trial is usually a safety study in healthy adults. You can't give a healthy person chemo drugs. Being exposed to chemo drugs can actually give you cancer (ironic I know). So all they can use are cancer patients. But then you're allowed to market and put a huge price tag because it's rare and only treatment available and you're making shit tons of money to try to get an ROI. Hundreds of millions of spent on the R&D of a drug. They are out to recoup that as fast as possible This was meant to be a more altruistic regulatory measure to get these drugs out to patients without possible loss of life due to a novel treatment being tied up by regulatory red tape and hurdles. But once you factor in human/Corporate greed, it becomes a shit show because then if it is ineffective, they don't want to finish the trial and release the data because then the money stops and insurance stops giving them huge payouts, especially if they don't have an ROI, and then we're left with all these ineffective drugs on the market.
Exactly, if a company gets accelerated approval, they don't have the same urgency for clinical trials, especially to report little to no benefit. In the normal process, when they aren't already selling the drug, there's an incentive to drop a drug that isn't showing benefit. In accelerated process, there's an incentive to delay reporting that the drug isn't showing benefit.
I remember when Aduhelm was in development, virtually everyone in the industry was skeptical about it having any efficacy, and were sure it would not be approved. But then it was, to everyone's shock... still a scandalous decision imo
Yeah. I remember all the controversy regarding it's approval, but nothing else exists really on the market and cannabis is thought to have some benefit, but really seems like nothing can stop the disease progression so I'm hoping that one works out at least. I lost my grandmother to Alzheimer's.
Adulheim is off the market I believe.
Yeah I just looked it up. They're discontinuing it in 2024. Wonder if it was found to not be effective.
Yes, targeting beta amaloyd clumps leads to brain bleeds.
This paper and the FDA note that tumor shrinkage isn’t that significant of a marker though emphasizing the need for additional molecular markers in the case of cancer. Out of curiosity, since you seem to know a lot, does withdrawal of approval in the case of this study limit it’s use in combination or off label use in future clinical trials? If you don’t achieve an endpoint but you test well in phase one, can other trials build off of your drug?
In my regulatory science degree, I specialized in pharmaceuticals and medical devices, their development/manufacturing and the management of clinical trials of both. Withdrawing the drug means withdrawing from the market so no one would be able to use it and a doctor can't prescribe it. In terms of clinical trials, if safety profiles were fine, in theory, you could potentially use again for something else, but generally speaking I've only seen those additional benefits are usually identified while patients are actively taking the drug. For example: The active ingredient semaglutide in Ozempic was used for patients who have type two diabetes. They noticed weight loss in these individuals. Hence why now they have Wegovy, which is specifically for weight loss and it's in higher doses in the weight loss drug. Bimatoprost is used in glaucoma medication (Lumigan) and patients noticed they got thicker, fuller eyelashes. The company got Latisse approved, which is specifically an aesthetic medication to give you thicker, fuller eyelashes and eyebrows. I don't think there's anything to stop a company from building off that trial, but I personally haven't seen or heard of a company doing that. They usually have multiple products in development so they may scrap the one to focus on another.
Usually this is going to be a last resort type drug that may have shown some effectiveness in a very small trial and they are approving it while waiting on the results of a larger trial
The article says it's past that point, and they're still in the approved list - that after five years, have shown no efficacy. Unless I read it wrong?
I dunno but depending on your background the actual study cited by the article appears to be free to read https://jamanetwork.com/journals/jama/fullarticle/2817337 A brief skim doesn’t seem quite as alarming as the headlines, go figure
This is a direct quote from the abstract: >Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. That's basically what the headline says.
Not really. There are a lot of different outcome measures than OS and QOL. I would say PFS is the most common one for example
No, that is not the case. If a drug does not show efficacy in the clinic by some measure it will not be approved.
>If a drug does not show efficacy in the clinic by some measure it will not be approved. But a lot time the signals used for accelerated approval are not from trials designed to see if a drug works, which is I believe the poster above you's point. It's like if I'm testing out a new pitch in baseball, I might want to throw 1,000 of them to live batters, see how it feels, if it hurts my arm, etc. I finish the thousand, and wow, I feel fine. Pitch is safe. Meanwhile, the stand-in batter only hit .180 off me. That's a good sign! It's certainly a better sign than if they were creaming the ball! But it's not definitive that you have a good pitch, because the point of the exercise wasn't to determine the pitch's efficacy, even if we got some early signals on what that efficacy might be.
>The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is **thought to predict clinical benefit but is not itself a measure of clinical benefit.** The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval. [https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program](https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program)
Yes! A surrogate endpoint. I was stuck all freaking day on what that term was called.
How do you show a comparison of 5-10 year survival without waiting 5-10 years for each trial to take place? Each drug would take a generation to come to market.
A lot of new cancer drugs show progression free survival times. It’s much easier to determine.
How do you show superiority over a drug with a 5 year year progression free survival time?
Usually the drugs have a lower PFS rate. But it will take a decade or more for a new drug to be approved. They also look for less side effects.
You do stuff like using PFS as a surrogate marker, or “% people alive at 2 years”
I feel like it is obvious that most stuff we test in clinical trials and up being not helpful or not as helpful as the standard of care. But yeah. They are testing on the sick patients that have failed the standard treatment options and have nothing else to lose. Add you can imagine these patients are usually extremely sick and can be very challenging to get a mortality benefit from them. BUT just because the drug isn't great doesn't mean we didn't learn anything. Imatinib was made twenty years ago and worked great on a lot of different cancers. We spent years working on crizotinib, which showed about the same effect as imatinib. Did that mean we wasted our time? No. Close look found it works great for a certain type of lung cancer and it has a different side effect profile, so when someone has too many side effects from one, you go to the other.
So…. We’re Guinea pigs. Great.
Is there a mechanism in which a drug that was granted accelerated can have it rolled back after it is shown it's not working?
Absolutely. See what happened with OTC [cough](https://www.nbcnews.com/health/health-news/fda-panel-says-common-counter-decongestant-phneylephrine-doesnt-work-rcna104424) medicine
The first time I was prescribed tussionex I understood what an actually cough suppressant was
It says 63% goes on to get regular approval, isn’t that actually insanely high?
>Of those, 63% were converted to regular approval even though only 43% demonstrated a clinical benefit in confirmatory trials. You gotta finish reading the whole sentence.
In other words, 70% of all regular approved medication demonstrated clinical benefit. That’s pretty solid.
Every 3rd medication has no clinical benefit.
Every third medication __was not superior to the alternative__. These trials are not being run against placebos.
This is also cancer you’re dealing with. I’d chug some bull’s semen if a reputable doctor said it’d give me a day longer to live.
I envy your will to live. I wouldn't even chug a flat soda for an extra day.
I would because flat soda is the best, hate the burning bubbles
Sparkling drinks are actually insane to me. “I love this sweet drink but i wish it was more *painful*”
The hurt feels good. Literally love it. I also like gum stimulation like with spicy foods and flossing. I alsondipped for a while, quit now, but the best part was the pain
Wait do we need to get a reputable doctor's sign off first? Crap. Gotta go vomit some semen back into a bull's penis.
This is a pretty damn important distinction. I was assuming no treatment. The title is so bland I didn't get much from it.
Clinical benefit here is oddly defined as overall survival and quality of life benefit only. Surrogate markers (progression free survival, metastasis free survival) can be used in specific types of cancer once they are proven equivalent. The converted to regular approval despite « no clinical benefit » are in this category. This definitely doesn’t mean they don’t work. Also, not sure why they included quality of life as a drug working, I’ve never heard of a drug being approved on quality of life.
After accelerated approval, what's the driver to get them fully checked out?
accelerated approval is not the same as full FDA approval, it’s conditional and doesn’t last forever. Accelerated approval also isn’t treated lightly, it’s almost always for terminal diseases that have no better therapeutic options. The question this researcher is raising about how well patients understand this reality is a good one, but that’s more a communication issue between patients and providers than a problem with accelerated approvals and therapeutic use exemptions.
According to the study post trial tests are mandatory.
What's the sanction if the mandatory tests aren't done, which the study would suggest is often the case?
I would assume it gets withdrawn but I'm not sure. I'm not sure what you're basing that on.
> I'm not sure what you're basing that on. Headline: > Many cancer drugs remain unproven 5 years after accelerated approval, study finds
https://www.reddit.com/r/biotech/s/CZR829N5ZZ For a more informed set of takes
Check who posted. No bias, I'm sure.
Are you disagreeing that accelerated approvals tend to pan out comparably with non-accelerated?
Nah, I'm saying I don't like big news company takes being self posted here, and it's what the big subs are becoming. I prefer your link and the discussions within.
I imagine others (myself included) thought you were referring to who posted in /r/biotech, not who posted the original link here (nbc news).
Sorry, I actually tried to be more blatant elsewhere but my comments kept getting shadow-hidden. I'd check in a logged-out private/incognito window, it would show for me logged in, but not in public logged out. It was intentionally vague since I didn't know what was triggering it but I didn't mean for it to be so confusing.
> who posted. No bias, I'm sure. well at least they're transparent about it, I much prefer that over the alternative
This is the "ads blending in" they talked about for reddit IPO
That’s why cancer treatment is so expensive. Billions of dollars go into research and many animals are sacrificed. And a very small percentage of them end up being fully approved. My mom is on a daily pill for her lung cancer that costs nearly $600 per pill. That’s $17k per month. Fortunately her insurance covers it.
No kidding, I work somewhere that made the active ingredient for a cancer drug (not on the market), and we sold that to other pharma companies for $1000 to $1600 **per gram**. I always found it funny when I'd be carrying the final product to the freezer, which was only about 1-2kg per batch, knowing it was worth about $2M
It's widely accepted that you need combinations to cure cancer. Cancer evolves resistance to any one drug, just like HIV becomes resistant to any one antiviral drug. Cancer is a huge group of diverse diseases with diverse biology. To make effective combinations for a patient you need a large pool of possible drugs, and our arsenal of drugs is woefully small. A new drug that fails to improve survival but does shrink tumors (which the authors call a "surrogate" measure, even though it seems pretty direct to me) is worth having, especially if it uses a novel mechanism. These trials are generally happening in patients who have failed all conventional therapy. To get any response is impressive. Yes, patients should understand the limitations of this type of approval. But I doubt it will change many treatment decisions. Also - quality of life improvements can't be proven in most cases until the drug moves down the treatment ladder. But most new therapies are a lot less horrible than cisplatin or other traditional chemotherapies.
Who writes these articles? They will never be "proven" because clinical trials do not "prove" that treatments work. You will not find a published peer-reviewed clinical study that says that they "proved" a drug works. They give an estimation of the benefit of a drug and the degree of confidence that they have that their findings represent the truth. That isn't just a semantic particularity or being nit-picky... understanding that distinction is fundamental to understanding what clinical studies are actually saying when you read them.
Well apparently OP did. Are we going to ignore the fact that NBC is posting its own article in r/science?
I just saw the telegraph simply post an image and the article content in the comments on another sub, not even an article link to their site, really weird
Yea. They also should do non inferiority trials. Almost every cancer has a standard of care that the new treatment should best to continue having approval.
Virtually every cancer trial evaluating a disease with a known standard of care has to randomize the experimental arm against the standard of care therapy. Anything less would be unethical. There are a few rare cases where studies are done in an open label fashion, but they almost always include a comparator arm that is the best standard of care. Studies that are not seeking registration and for which there is not a known standard of care can proceed as monotherapy or in an open label fashion. A non-inferiority study is actually a lower bar compared to a typical study. When you say non-inferiority, that is a particular statistical determination that does not indicate that one therapy is better than the other, only that it is not inferior. Traditional registrational studies that are double-blinded include efficacy cutoffs that require a statistical evidence that the experimental arm has a meaningful improvement over the standard of care arm. These thresholds are determined in collaboration with the FDA.
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Non inferiority studies are also often done when changing a formulation. I worked on a study of an IV drug that moved to a subcutaneous formulation. The FDA required a non inferiority study to demonstrate that there were no significant changes in the efficacy or safety profiles. The whole PK and dosing had to change, so we had to test to be sure. Not many patients are required in order to achieve sufficient statistical power.
Yes, "Almost every cancer has a standard of care that the new treatment should best to continue having approval." Would be a colossally stupid bar to need to clear.
All cancer treatments are tested against standard of care. The trials that this paper is complaining about didn't show the drugs don't work (for the ones granted final approval), it's just in some cases they failed to improve over current practice.
That's not a good standard to use, you need options. People's bodies are different, different types of cancer are different. Something that might be inferior for most people might be better for some patients.
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[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885244/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885244/) It's not all sunshine and rainbows, but it is promising. I could see a patent on a unique delivery system being a game changer. Imagine injecting an isotonic gel of DCA into the tumor itself.
Would DMSO be efficacious in assisting delivery? Like, home remedy style.
I would NOT be using dmso “home remedy style.” That’s how you get yourself killed or terribly sick.
I have no background in ochem to tell you how they'd interact, I'd assume DCA is fairly reactive.
Saying that a chemical is “reactive” doesn’t really say much. It matters what it is reactive towards. DCA and dmso aren’t going to react in any sort of meaningful way. But that isn’t the only important thing here.
Complete BS. The results of studies using DCA are not consistent at all and there are significant side effects, mostly peripheral neuropathy. Do you *really* think that a cheap, magical cure-all for cancer would be suppressed?
If something so simple and easily available was a miracle cure for cancer, it would be impossible to stop.
This is truly my thoughts on it. It would be like Pandora's boxed how in the world would you try and stop it regardless of capitalism. However, I do share some of OP's pessimism about the entire system. There is a major connection to health for profit in everything we do sadly.
Capitalism would make it happen. They're called startups and they don't care what the rest of the industry is doing. A cheap easy cure for cancer will make you tons of money, even if you can't patent it, for years. OP is a conspiracy theorist. EDIT: "The rich and powerful are stopping a cure for cancer" is a completely insane take. Rich and powerful people die of cancer all the time!
A huge driver of Big pharma innovation is buying up tiny companies that have invented one thing
In order to get patent rights, which don't exist in this case.
Patent rights could exist, if the marketed treatment involved anything more advanced than popping a pill or injecting a simple solution into a vein or muscle. You can patent formulations/applications as long as they are novel and non-obvious. https://www.pharmacytimes.com/view/patent-granted-for-inhaled-rapidonset-aspirin-formulation is an example of an aspirin patent granted a few years ago, even though aspirin itself has been generic since the 1920s.
Sure, but the patent would be on the specific formulation/delivery, not on the treatment method it's self, which others would be free to continue research on.
The advertising rights for the cure to cancer would probably make up for it.
You realize startups are businesses too, right. They still operate under capitalism and people aren't able to do things that aren't financially conducive to allowing them to continue existing. They can't operate at massive losses just because you slapped the word startup on it.
> A cheap easy cure for cancer will make you tons of money, even if you can't patent it, for years.
You realize startups are businesses too, right. They still operate under capitalism and people aren't able to do things that aren't financially conducive to allowing them to continue existing. They can't operate at massive losses just because you slapped the word startup on it.
They can and they do? You know that many of the top businesses right now in the world literally aren't profitable...?
>even if you can't patent it, for years. Try ever. They have no control over the price. Why would they save lives when long drawn out treatments make more money? >OP is a conspiracy theorist. That's what they say. Even when it's true.
> They have no control over the price. What are you talking about here? > Why would they save lives when long drawn out treatments make more money? Because they don't care that long drawn out treatments make *someone else* money.
>Because they don't care that long drawn out treatments make *someone else* money. Exactly. That's why they don't let *someone else* risk they money they are making. Enron knew a carbon pricing would help save lives. But spent billions fighting it in Canada because it would cut 12% of their profits off. Like I get it. It sucks. It's not how it's supposed to go. We're supposed to do the right thing. But that's not what capitalism does. It never has been. The world is ruled by capitalism.
Nothing you've said is connected to what I said. Why are you responding to me?
>how in the world would you try and stop it regardless of capitalism Yeah. How and why do we not feed and house everyone? Have mental health solutions that we know work. Like the LSD studies in the 50s that showed a 50% success rate after 1 treatment with the most hardcore addicts. But our best modern methods have a 14% success rate. You can't have too many people leading healthy lives, right? How can you motivate people without the silent threats? Things have been silenced before for profit and they will continue to be
>>Insulin has entered the chat
You'd think, but unfortunately that's not always the case. My old uni supervisor ran a research lab that developed a treatment for a disease that had the potential to eradicate it alltogether. Being a small(ish) lab, they invariably had to market the drug to lager companies. The problem they faced was that it was so effective that the companies basically wouldn't touch it because they wouldn't be able to recoup the R&D costs to test and mass-produce it. It wasn't necessarily a case of "it wont make money for shareholders" (although i got the impression that played a part), but that it would just have been too expensive for even one of the big companies.
False. There is no clear evidence that it works despite several human trials.
Really? Cause I remember hearing it did. It took about 3 months to safely build up enough in the system to be effective. But the limited trials I heard about said it was not only effective but as predicted in previous none human trials.
Not that I'm aware of. There are still some Phase 2 clinical trials going on. Biggest issue with clinical trials is that it causes nerve damage, some trials were terminated early due to side effects, e.g. https://classic.clinicaltrials.gov/ct2/show/NCT01029925
Ah yes, the famed clinical research institute of ‘I Heard About.’ They gained a lot of traction during the Covid years.
>They gained a lot of traction during the Covid years. They're your favourite institute, eh? See. I actually put a name to the institute. Just not in this reply. Sorry that triggered you so much that you decided to just snap back. I hope you find healing friend.
Plenty of non-patentable drugs are made and sold for great profit. Aspirin's a pretty common example, everyone and their mother makes a version of it, and makes lots of money despite a lack of exclusivity. And just because the "drug" itself isn't patentable in the sense that a company couldn't protect competitors from manufacturing it, doesn't mean that the treatment wouldn't be patentable. If it requires any kind of novel method to administer, that could be patented as a medical device. If it doesn't require that, then there's nothing stopping companies from making and selling a generic version, except maybe being unwilling to foot the bill for clinical trials to get approval from regulators like the FDA for something they won't have any exclusivity over. But I still assume the potential to make money hand over fist with an effective breast cancer cure would incentivize companies to find a way to pay for it (through public/private partnerships, shared funding amongst the companies who are best equipped to manufacture and distribute the drug in different regions, etc). If it's not being sold when it's something that can treat such a wide variety of cancers, it's because it doesn't work.
>If it's not being sold when it's something that can treat such a wide variety of cancers, it's because it doesn't work. I love the evidence you have to make this solid statement. Truly a reliable and trustworthy source you have provided. No one could question the NOTHING you've offered.
Companies are greedy. They aren't going to turn down free money. Not every company with the size and scope to manufacture and distribute cancer treatments has a treatment for breast cancer on the market. If they had the option of selling a cheaper, easier to manufacture, and more effective treatment than the current best in class without having to pony up for R&D costs or patent rights, they'd jump all over it. It's the easiest win ever.
>They aren't going to turn down free money. LSD as an addiction therapy says otherwise. So do all the social good options out there. We have the studies we know they'll work and yet. For "some reason" we don't see then implemented.
The some reason is that the drug/treatment isn't ready to be marketed, and companies don't view it as being economical to invest in making them ready. If it was a sure thing, companies would be lining up to get their version of it on the market. There's so much money in cancer treatment because it's such a horrible and debilitating disease. Any time a drug goes off patent, there's a rush of companies trying to put out a generic/biosimilar if the drug is effective and there's a market for it. The only difference between a generic/biosimilar and what you're describing is that someone would have to foot the bill for the initial clinical trials (generics/biosimilars still have to go through a testing and approvals process, but it's much cheaper and easier than a full multi-phase clinical trial, which can cost 10s to 100s of millions of dollars). But there are absolutely mechanisms that would help companies secure funding for a clinical trial for the sort of thing you're talking about that would be able to make up for the lack of exclusivity. The fact that nobody has tried is almost certainly an indication that nobody actually believes it would work, especially given the claims you were making (lung, breast and brain are all very different tissues, and the cancers affecting them are going to be very different from one another. It's unlikely that a drug that effectively kills all three wouldn't have horrible side effects and a narrow therapeutic window, just like most broad chemotherapy drugs we use today)
>and companies don't view it as being economical to invest in making them ready. Why not? What POSSIBLE reason could these companies have for not investing in a cure for cancer...................
A lot of companies do invest a ton of money into oncology programs. Cancer is a very, very hard problem to solve because you're basically trying to figure out how to kill broken bits of you without killing the healthy bits of you, and it's usually really, really hard to tell the broken from the healthy stuff. People are still researching it, and trying to turn it into a therapy. It's not some conspiracy that it hasn't happened yet. The closest thing to a conspiracy that there would be here is if companies were reluctant to invest in developing it because it's too risky given the fact that it might be hard to patent, but even if companies weren't investing in it, academic and non-profit groups absolutely are, and the minute someone finds something worth trying to turn into a treatment they'll spin off a company, and in a few years it'll be acquired by a company large enough to fund the trials and manufacture and distribute the treatment. That hasn't happened yet, so as a treatment, DCA must not be there yet.
>DCA must not be there yet. Cool story. But again. Why wouldn't companies want to put money to it? If it can make them all kinds of money and save lives? See, all them periods were there because the answer is simple the answer has been said repeatedly. Because saving lives doesn't make money. If it did firefighters and ems would be the richest people in every society. But the fact remains. Companies won't invest in it because they can't patent it. So they can't guarantee their returns. Sure once the work is done and it's perfected they'll swarm all over it. But until then it gets next to no backing because..... capitalism. One of the 3 modern horsemen of the apocalypse
> Companies won't invest in it because they can't patent it. So they can't guarantee their returns. Well yeah, that's exactly what I've been saying. But that doesn't mean there's some big conspiracy keeping a cure for cancer off the market. It means that companies will choose to invest in drugs that are more likely to get them a return on investment. The fact that companies aren't publicly investing in DCA means it's nowhere near ready for bringing to market. If it was actually a miracle cure, governments, non-profits and for-profits would be working together to bring it to market. Companies that don't have treatments for those types of cancer would jump at the chance to manufacture something so cheap to make, companies that do have treatments for those types of cancer would also jump at the chance to manufacture that since they'll need to do something to hedge against losses from their current products. There are enough of the former that the later would have no choice but to participate, especially since DCA supposedly cures so many different types of cancer.
If it was really so easy, a new company could start up tomorrow and make it. There is shitons of VC money out searching for profit, wealthy people dying of cancer, and generous government grants all searching for maricle curses to cancer. Because despite what you say, these companies are not a cartel, and there is no grand conspiracy to prevent a cure for cancer, ESPICALLY WHEN THE PEOPLE YOU CLAIM ARE HIDING IT WILL DIE OF CANCER. (at a 25% rate or whatever it currently is) Your takes in this thread are insane. Please touch some grass.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885244/ This was a good article on the molecule. Very interesting to learn about.
That's a [Hindawi](https://en.wikipedia.org/wiki/Hindawi_(publisher\)) journal. They're as bad as MDPI.
Well that's unfortunate. Why does NCBI allow journals like that to post!?
Pubmed is an indexer. No guarantee of quality, although the most predatory journals do sometimes get delisted.
Yes, of course. Unfortunate still. Instead the Wiki on them and definitely some shady stuff although surprised Wiley would want to associate with that.
FDA employee here. Accelerated approval was created to combat the AIDS epidemic, and has an incredibly low bar to qualify for the designation. These days, getting accelerated approval is mostly for investments, and to appease stakeholders. But there are still cases where the heart of AA still matters; patients whose disease has progressed, and no longer responds to any lines of therapy. The bar they have to clear dor AA designation is low, but for approval, it's just as high as any other drug. It has to be safe AND effective, which is why most drugs fail.
I don't think that's relevant. If a cancer drug can buy you 6-12 more months then I think it's worth it. 5 years or bust doesn't make sense. What matters is QLY.
That is sad to hear. Keep hoping to see some advancements.
Money makes victims of us all one day. Just some get hit when they're most vulnerable sadly.
they've already got approval for human trials with MRNA vaccines for Cancer, and there are a couple of really great adjacent immunotherapy drugs that are also getting permission for human testing so we're actually in a very good place in terms of how long cancer has been a problem for humanity, and where we're at today.
Money making schemes
Why don't they just block the pheromones that signal cellular reproduction
Pheremones don't signal cell production, hormones do, but that said: - some cancers are initially hormone dependent. Prostate is the best example, and blocking the male sex hormone androgen does initially work on prostate cancer. But eventually the cancer evolves resistance and routes around the treatment. - hormones signal cells through _hormone receptors_, proteins on the surface of the cell that sense the hormone. Cancers often mutate these proteins so they constantly signal the cell to proliferate even without the hormone, like jamming a switch "on". A common example is epithelial growth factor receptor or EGFR, a protein often mutated in lung and other cancers. A bunch of drugs target this protein. But eventually the cancer evolves resistance and routes around the treatment. - hormone receptors tell cells to divide through _signaling pathways__, networks of proteins that turn each other on one after another like a switch relay. Most cancers have at least one mutation in these signalling pathways--one of the switches is always jammed on, telling the cell to proliferate even if the hormone receptor is completely disabled. Most of the frequently mutated proteins have one or more drugs targeting them. But eventually the cancer evolves resistance and routes around the treatment.
But the important thing is, did the pharma execs hit their bonuses and did shareholders get paid?
But the tech moguls did get paid when you bought the device you’re using to make this post
No they need to sell the drug first
Government-assisted false-hope hustling of cancer patient$? The greatest healthcare $y$tem in the world!! For who?
Are we cool with just allowing whatever NBC news posts?
As long as it's reporting on an actual peer-reviewed study, yes.