My dad was fortunate enough to get into a trial at Sloan for Obinutuzumab for Chronic Lymphocytic Leukemia. At the moment, after 6 weeks of treatment, the percent of cancerous cells in his bone marrow has gone from 95% to 5%. The treatment was very intense as it overloads the kidneys on the first few treatments due to the dramatic amount of cells being flushed out. This is a cancer for which there was not much treatment previously other than extreme chemotherapy which still left little hope for complete remission. A family friend was also treated for Non-Hodgkins' lymphoma on another drug trial and she's now in full remission.
my uninformed impression is that there's a lot of new cancer treatments happening now that can turn the tide for a lot of types of cancer.
For leukemia, there are a lot of promising new treatments and clinical trials. For metastatic solid-state tumors, much less. We're still in the dark ages of cancer treatment.
Imatinib (Gleevac) revolutionized treatment for patients with chronic myeloid leukemia (CML). Prior to the drug’s discovery, CML patients generally had seven years to live (possibly less depending on how advanced the cancer was). Now their lifespan mirrors the general population.
I’d highly recommend the book The Philadelphia Chromosome if you’re interested in learning more.
I am currently taking a similar drug for Myelofibrosis on a clinical trial holed up after a stem cell transplant here at MD Anderson Cancer Center. It's called Itacitinib, and is supposed to prevent GVHD. It's by the same company that makes Jakafi (brand name). These are expensive drugs for sure, and my DR is running the clinical trial. Just wanted to chime in from the inside. ;p
BTK inhibitors are technically in 3rd gen (noncovalent) already if you can get in the trials (which are very promising considering they use the same mechanism).
That's great for your dad. Thank you for also distinguishing between types of cancer and the nebulous term cancer, many people don't make the distinction.
Probably a decade ago a friend of mine passed from Acute Lymphocytic Leukemia in his 20s. I'm not sure what the differences are between ALL and CLL (other than knowing the differences between acute and chronic in a more general sense of course) but glad to see they are making at least some progress.
the chronic form is often written off when first diagnosed as "it will never affect you" - it can take decades to cause bigger problems. Dad's 80 and it's been causing bigger problems for some years. It would be surprising if there aren't new treatments for the acute form you mention as well.
> It was a small trial, just 18 rectal cancer patients,
just 12
"All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. "
As with most experiments there's a control group (6 patients). The original statement of 18 participants is correct along with yours of 12 patient treatment group.
But then I guess it is slightly less surprising that all 12 people had remission, rather than all 18. (Or if all 18 had remission, then that's amazing but might not be to do with the drug.) Maybe it is still a great result, just slightly less significant.
You're correct. We'd expect to see more extreme outcomes with smaller sample sizes. The question is does this translate to more drugs when administered early which was the real reason for this study.
A placebo control group when there is an established standard of care? That sounds highly unethical. The above link to the abstract don't mention this and I don't have access to the full text paper. If you do can you clarify what the control arm received?
I intentionally avoided using placebo group. The control cohort may not have had cancer at all
_____________
The plan is to enroll six patients with MSI, regardless of their primary cancer diagnosis. This cohort will serve to generate hypothesis and initial data to plan a larger study. All analyses from this cohort will be exploratory
I appreciate your good intentions, but you should consider not writing things on the internet like this - as both of your posts are effectively misinformation.
> As with most experiments
This isn't true. It's absolutely standard in earlier trials of investigational agents to not have any sort of control arm.
> there's a control group (6 patients).
This isn't true. Within the study you posted, there are two different cohorts, with different patient types included.
> The control cohort may not have had cancer at all
This isn't true. The group you're calling a control cohort (cohort 2) must all absolutely have cancer, and are all actively treated with the study drug (TSR-042).
I’d encourage comment OP to continue writing comments online, so that you can learn. The damage done in misinformation here is probably extremely limited.
If comment OP was trying to misinform on purpose, it’s a different story as there’s no opportunity for improvement there.
> At the time of presentation, 18 patients were enrolled on trial.
> Results among the 14 patients with at least 6 months follow-up showed a complete response among all patients (95% CI, 74-100), with no evidence of tumor on biopsy, digital rectal exam, endoscopic visualization, fluorodeoxyglucose-PET or MRI. The other four patients are responding to treatment.
70% of Phase 2 trials fail and 50% of Phase 3 trials fail[1]. Why should the default to be to approve drugs in the early stage of human experimentation?
Here are some interesting case studies of drugs graduating from Phase 2 trials only to fail Phase 3 trials on efficacy and safety grounds: https://www.fda.gov/media/102332/download
Because (at least) for people with a high risk of dying, and operating under well-informed consent, that decision should be between patients and their doctors alone.
If we allowed any type of experimentation on dying patients as long as there was consent, dying patients would end up getting used as a Guineapigs by companies trying to get a lucky indication. It would certainly benefit the families left behind financially, but it would not be pretty. “Here’s a million bucks, please take these 40 drugs that will certainly kill you, but we’ll learn which one we should continue with”.
And why even do toxicity studies or phase 1 and 2 trials? It’s cheaper to pay of poor people who are on the verge of dying and just pushing them over the edge.
The decision should be just because a patient and a doctor, because the consequences of such decisions are more far reaching than just those two.
We have a well established framework for what a drug needs to prove before they can reasonable be allowed to be given to any human being, no matter their situation, and that barrier of entry is there for a multitude of good reasons. Discarding it just because a specific patient is at risk of dying or because you can get consent is not helping patients.
> In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose bone marrow transplants, thinking this would lead to better long-term survival. However, it proved completely ineffective, and 15–20% of women died because of the brutal treatment.
> You are very optimistic. Medics will sell expensive snake oil treatment
I think you misunderstood. My point was that it would benefit the families because a company would gladly pay a million bucks to give a dying cancer patient the first human dose of 40 drugs they haven’t yet done any testing on, just to get quick human feedback.
The “patient” in that scenario won’t likely get any benefit from the money, but the family they leave behind would.
Obviously this is not something we want to actually see happening, but the cynic in me know that if a company can save billions by skipping all trials and going straight to “dying human” they will, and they’d be happy to pay the expendable subject a million or even more, they still come out net positive.
There are certain choices we as a society do not want to allow you to make even if both you and the other party concents. Just because your dying and for instance would be ok with being hunted for sport in a Netflix special in return for a million dollar payout to your family does not mean we should forgoe all morals, logic and law and just accept it.
Allowing dying patients to make those sorts of deals with pharmaceuticals is just as horrible in the grander scale of things, they just stand to save a lot more costs and gain a lot more profits than Netflix would in a “Running Man” scenario.
You might be able to make an informed decision. Most people (and most doctors, for that matter), are not qualified to accurately judge the many uncertainties, biases and trade-offs present in drugs only tested in early stage clinical trials.
And to add on top of that. If pharmaceuticals could buy out dying patients at a fraction of a cost of even the pre clinical trials to get first human dose there would no longer be such a thing as “early stage clinical trials”
There's definitely a case to be made for early access to drugs for certain terminal illnesses in cases where there is compelling evidence that the drugs will pass Phase 3 trials. But, that should hardly be the 'default' as OP suggests.
Because it would degenerate into pharmaceuticals selling false hope in exchange for lab rats that are too far along to be saved even if the drugs work.
That being said I disagree with prescription pads. I should buy antibiotics for my kid without waiting four, five hours to be seen and processed
> I should buy antibiotics for my kid without waiting four, five hours to be seen and processed
Disagree. Antibiotics should not be taken lightly, especially by kids. Doctors have been far too liberal in prescribing them even when unnecessary and this has caused people to think antibiotics are to be taken like vitamins.
This antibiotic abuse causes issues that are out of scope to discuss here.
And yet the Dr gives them out in exactly the same circumstances as I would if I could. Perhaps more liberally, since Im far more concerned about the consequences to my kids of destroying their gut flora.
You said in a sister comment that your doctor wouldn't prescribe antibiotics until a culture came back. Isn't that precisely the opposite of giving them out freely in the same situations you would?
Yes, in your case the culture came back positive. But, you're not psychic, you didn't really know that, and you're biased by the fact it's your own child.
Do you know how many Dr.s a parent deals with? After hours, you don't go to your family Dr. This year alone Ive probably seen a dozen Dr.s
Ive had some Drs push antibiotics after they literally just said a persistent cough is probably viral.
Ive had my daughter with blood curdling screams told her urine came out negative and her urine would have to be cultured. They can culture it all they want but I didn't leave without the antibiotic. Guess how the cultures come out? Plural because it happened more than once and the quick test at the Dr. has a high false + rate. Btw, untreated UTIs cause scarring.
Btw, Dr. dont pearl clutch when it comes to their loved one. My colleague, who's married to a physician, got started on antibiotics for Lyme disease before the cultures came back positive. Just in case.
"But, you're not psychic, you didn't really know that,"
No, Im not. I just happen to have a neural network on the top of my head with hundred of millions (billions?) of years of evolution to spot trends.
You are correct. I arrive at conclusions based on my life experiences and what I've learned along the way.
We literally give industrial quantities of antibiotics to animals. So antibiotic preservation is not an honest reason to lock them up
Tylenol and Advil can very quickly mess up your kid's liver and kidneys if you misdose. Yet, they're over the counter. So safety does not appear to be an honest reason either.
Ironically, statistically considering the forum, most ppl who are against me on this thread believe in drug liberalization including opiates; the one class for drugs I would keep behind the pharmacist's counter.
Btw, antibiotics are available over the counter in Europe. The ones Id use and feel comfortable using
> Btw, antibiotics are available over the counter in Europe. The ones Id use and feel comfortable using
What are you talking about?
> Over-the-counter (OTC) sales of antibiotics is forbidden by law in all countries, but it is allowed for some
specific formulations (creams in Norway and Denmark or eye drops in the UK)
I would agree that drugs which have passed Phase 2 trials should made available to "mercy" patients during Phase 3 trials for patients that were not able to get into the trial...at cost to the pharmaceutical company that hopes to sell the drug/
This would eliminate the profit motive that other commentators have noted would be a huge issue.
The alternative is worse, unfortunately. See the recent Aduhelm debacle for example, with big pharma profiting from desperate people, with a drug that doesn't work.
Pharma would market a phase 2 trial drug as a “potential revolution in treatment. Only a select few can receive this treatment and as a result it costs 10x more than existing drugs. Ps. We don’t guarantee results.”
Fewer people dying and more people overpaying for ineffective treatment is potentially a good tradeoff. As a society we already funnel massive amounts of cash to new medical treatments, we just do it in a really inefficient way.
(Not the OP) In a macro sense, I'd agree with you; no stranger to having to weigh the risks/rewards of experimental drugs.
But at the same time, I do get why extensive approval is needed - deaths can and often do occur from allergic reactions and/or side effects to medicines, and the idea is to hopefully lower the ratio of that happening. At some point more people "will" die from allergic reactions/side effects than the time it takes to get approval.
I mean if they've already tried everything else and nothing on the horizon and I just heard 12 of 12 people with same cancer as me had gone into remission after treatment? I'd probably be more than happy to become #13
In the clinical trials I have been a part of the manufacturer pays for the drug and all related study costs. They even pay you a stipend for commuting, lunch, etc.
The name of the drug ends in "-mab" [0] indicating that the drug is based on monoclonal antibodies [1,2]. Those antibodies are tweaked to bind to cancer cells which makes the immune system attack the cancer cells.
IIRC, in this particular case the antibodies bind to immune cells. Immune Checkpoints are a mechanism that keeps the immune system from attacking the own body but in cancer it can also stop the immune system from destroying the cancer. The checkpoint inhibitor antibodies remove these restrictions and allow the immune cells to attack the cancer. (The price is that they also become free to attack other things they shouldn't; autoimmune inflamations are common side effects.)
Several varieties of T cells are very dangerous and like to murder other cells. In order to prevent them from going on a rampage, they have a switch called PD-1 that calms them down. This prevents various auto-immune diseases in healthy people.
Some varieties of cancer cells release a PD-1 ligand that turns off T cells when they get close to the cancer. So the cancer can "hide" from the immune system.
This monoclonal antibody blocks PD-1 on T cells, turning them into unstoppable murderers. The hope is that they preferentially murder the cancer cells. Wikipedia says that ~5% of patients get dangerous side effects from blocking T cell PD-1, probably because the unstoppable T cells attack healthy kidney or liver tissue. But for people with specific types of cancer, the hope is that turning the T cells loose will kill the cancer first.
That is the function of checkpoint inhibitors, according to an explanation I got from a cancer researcher after asking a similar question.
Essential, cancer cells convince the immune system not to attack them, so these inhibitors target the mechanisms by which they do so to get the immune system to take note of these cells. Hope someone more knowledgeable will correct me if I'm wrong.
Cancer cells (and our own cells) express PDL1. Our immune cells touch PDL1 with their PD1 and if this connection works then the immune cell does not kill.
If the connection does not work (PDL1 or PD1 absent) the immune cell will kill the target cell.
Couldn't read the article but yea, if it's a small molecule, most likely it's inhibiting some protein specific to cancerous cells. In this case, it sounds like it's blocking some protein that blocks human cells' innate ability to produce antigens, which signal to T-cells that they are defective and need to be destroyed.
Sometimes we understand the biology after we discover a treatment.
This experiment of treating cancer with checkpoint inhibitors before chemotherapy should be widened to all cancers where the CI is available and effective as soon as possible, as it can cure lots of lives.
I'm worried that it will take many years until that happens.
> I'm worried that it will take many years until that happens.
For good reason. If we detect cancers early, surgery and radiation are often very good nowadays--often allowing you to skip chemotherapy. And these are far less likely to kill the patient than a checkpoint inhibitor (which can overload your kidneys if it works or give you autoimmune diseases even if it doesn't).
The problem is that there are a lot of cancers we don't detect early-lobular breast cancer, pancreatic cancer, etc. And for things like intestinal cancers radiation is particularly bad.
These kinds of immune treatments are likely to get promoted first line treatments quickly if they really are this good--especially since they are likely to work on stage 4 metastatic cancers for which we don't have anything decent.
My ex girlfriend detected breast cancer early at age 28, but the doctors told her that she's ,,too young'' to have cancer. 1 year later on the checkup they said that it's too late (she has BRCA1 mutation). The last 10 years have been fighting with cancer, having about 10 operations on her, but the worst thing was chemotherapy (she said that she would rather die than go through it again, I think the dose had been too large for her probably as well, as she's 44kg). The cancer went away and came back multiple times, and it got so bad that we had to separate, but she's still my best friend (and I didn't find any other person to spend my life with).
She's right now on an experimental checkpoint inhibitor (stage 4 metastatic since a year ago), and it probably gives her another few months, but every time I see her I think that she only has a year left in her life and get sometimes frustrated that the experiments are not optimized to get the more effective treatments in earlier stage.
I sympathize. Cancer, especially in the young, is very tough. Patients really have to aggressively advocate for themselves, which itself comes with risks. And the treatments are devastating. The drug I worked on in grad school is really close to killing people to save them. https://en.wikipedia.org/wiki/Fluorouracil
But, recent work with immune treatments for cancer give me hope. I have not seen so many doctors and scientists say things like "the tumor just melted away" before.
I got to spend a couple of weeks as an internal medicine intern with a medical oncologist who incidentally worked at memorial sloan prior to coming to my university. You could tell how excited he was about the current state of cancer research and new treatments, especially with immunotherapy.
Wonder if docs will start off-label treating earlier with immunotherapy. There's tons of immune checkpoint inhibitors meant for different types of cancers and mutations.
This is misleading. Yes, the response rate is extremely high but all of this patients shared a mutation or a group of mutations in mismatch repair proteins (they were all MMR deficient, or mismatch instability high).
If I had to guess this is a huge marketing plot to bring yet another extremely expensive drug to the market. What is happening is that different drugs (ie different companies) take the space of a specific tumor (Keytruda for lung, Opdivo for melanoma, Tecentriq for liveer cancer) and Dostarlimab is going to claim the rectal cancer space.
> The medication was given every three weeks for six months and cost about $11,000 per dose.
That’s an $88,000 treatment for the medication alone. Given the apparent success of the drug, is it expected for the price to drop as the volume of patients spike?
Something I saw in drug pricing conferences is that there is a push to price drugs according to how much personal and social benefit they provide and how much a person would be willing to pay to extend their life or resolve a condition. An extreme example for that model, if a drug allow a kid to survive and have a productive life it can be priced millions whereas a palliative drug could be much cheaper.
This has nothing to do with research and cost of development anymore (if it even ever did).
But so two patients in different financial circumstances would both pay basically as much as they are able for a life-saving treatment, arriving at very different amounts, right?
- that sounds a lot like ransom?
- I think if they adopt a policy of price-discrimination to the point of literally taking you for all (or most) of what you're worth (or projected to be worth), we should turn around and apply the same reasoning to corporate tax rates.
I met a researcher once who was doing what appeared to be groundbreaking research on cancer care. He had this beautiful, tear-jerker story about losing his wife that cast a rosy, altruistic hue on his research. When he was asked what the device would cost, he cheerily replied "whatever the market will bear." That's always stuck with me -- the problem with American healthcare is the American interpretation of capitalism. Dude was living off of government research grants.
That's not the problem, that's the reason almost all medical development happens in America.
Rich people from all around the world travel to American hospitals if they have serious health problems, not to public hospitals even in rich countries like Norway. Public healthcare works (poorly) as a way to distribute existing treatment, but is worthless at incentivizing development. Really, the entire world is unfairly parasitizing on Americans to fund medical research.
Unless you are looking at outcomes of only the top institutions it's not really what he was saying. The US has a bad system for the average person for sure, but that does not mean that the US doesn't have one of the best systems if you can afford the best care. If you have medical outcome data that disputes that specifically I'd be interested.
Why would you think the best hospitals in the USA outperform any other developed country's best hospitals? Especially when those countries already deliver better average results across the board. Why do you have this belief and what is it based on?
Just google medical outcomes for any disease on a per country basis.
Do you really think the best hospitals in France or somehow worse than the best hospitals in the USA? Especially when the best hospitals in the USA still have the same fundamental problems as the rest of the American system?
It is extremely plausible that worst case, average case, and best case have different rankings - it's a little telling that you have no data and your only counter is to say that average should have the same trend.
I am aware that most of the cutting edge clinical trials in my field occur in the US. I have also seen people travel to the US for treatment of rare diseases. And I know that this isn't a surprising thing for the US in general, just look at our universities.
It's actually pretty funny that the only other response I got was someone saying that this is super obvious/true across fields in the US and thus not an interesting statement.
It is extremely weird that you think the best hospitals in the USA are not the same as the best hospitals in other developed countries. Especially given that their medical systems outperform the US system on a general basis.
I don't know if it is a weird American bias or what. I'd take a look at the bias there and this belief in American exceptionalism as it doesn't pan out in the data.
Cutting edge clinical trials and those companies are global in nature. I mean just look at the Moderna team and where they conducted those.
> The US has a bad system for the average person for sure, but that does not mean that the US doesn't have one of the best systems if you can afford the best...
That's basically the case for everything in America, so I'm not sure that it says anything remarkable about the American healthcare system.
Like can you think of anything else in America that you couldn't apply that statement to?
Or rather America is siphoning market by having monopoly. My father works in pharma factory and wages have not risen almost at all since 20 years ago when it was bought by americans (by bribe to gov). Some drugs got 10x more expensive while workers and patients got it worse. This was ultra scam but even after change of owners it’s basically the same.
Capitalism works only with competition. But competition is against capital owners short-term extractionism (or rather against ceos who feels need to justify their pay). IMO solution is to let workers vote on CEO pay changes and punish white collar crime better and many problems of capitalism might get solved.
EDIT: IMO it won’t work as long as globalization can be exploited to suppress working class and avoid regulation
> That's always stuck with me -- the problem with American healthcare is the American interpretation of capitalism. Dude was living off of government research grants.
Do the drug companies in Europe do any different though?
I mean, sort of? Except, not really, because, "what the market will bear" is determined by what governments can negotiate - there's no Medicare Part D tying their hands.
But the companies are still greedy in Europe. Zolensma one of the most expensive drugs is from Europe. Those companies sell it for what its worth. When Joe Biden proposed covid vaccine patent waivers, European leaders were quick to suck with with the corporations in opposition.
> That's always stuck with me -- the problem with American healthcare is the American interpretation of capitalism.
What should it cost instead?
> Dude was living off of government research grants.
Let's imagine his work comes to fruition. The drug is expensive but efficacious - is this not a good thing? Should the government have not helped fund this drug because now it's expensive?
The alternative is a world without that drug and without as much incentive to produce the drug. I'm not sure that's a good trade.
> Should the government have not helped fund this drug because now it's expensive?
If he wants to charge "what the market will bear," then he should fund the research through the market.
If he wants government handouts to do the research then the public deserves to get the benefit that it's paying for - we're not funding it to make some guy rich.
I'm not saying it should be free, but he's already opted out of the market, so he loses out on market pricing. Manufacturing cost plus some reasonable percentage for the creator.
I'm all for cutting subsidies, but the problem is that if you want risky things then investors might decide it's better not to invest and the drugs never appear.
The government (which is really a government of and for the people, right?;) gets what it wants - a new drug - and jobs are created, trade happens, taxes are levied, health improves leading to (theoretical) money saved, more hours worked, more taxes… There's no need to punish the creator by not letting them make money off of their creation just because the government was involved, the government is getting plenty out of their investment.
> I'm all for cutting subsidies, but the problem is that if you want risky things then investors might decide it's better not to invest and the drugs never appear.
So? Nobody has a right to free money. If investors don't want to fund the research, and the researcher doesn't want to share the results with the public, then no money for them. They can go off and work on something else.
> There's no need to punish the creator by not letting them make money off of their creation just because the government was involved, the government is getting plenty out of their investment.
You're putting words in my mouth. I said the cost of government funded drugs should be the cost of manufacturing plus a percentage for the inventor.
Second, that's not how government funding works. If the public funds a thing, then the public has a right to use that thing. If the inventor doesn't like it, then they shouldn't take funding from the government.
Funny to see a pro-corporate welfare argument on HN.
> Funny to see a pro-corporate welfare argument on HN.
It's not so that's your mistake.
> > I'm all for cutting subsidies,
You see, I wrote that. However, as we can see when I continue I am able to see the benefits to a system I don't agree with. It's called being reasonable and not strawmanning your opponent.
> > but the problem is that if you want risky things then investors might decide it's better not to invest and the drugs never appear.
> So?
So… I gave that argument right there. "the problem is that if you want risky things then investors might decide it's better not to invest and the drugs never appear." If your response to this is "So?" then you've just said "So?" to "the drugs never appear". Strangely unappealing.
> Nobody has a right to free money.
Aside from having not made that argument and it not being relevant, you're arguing that people should get free drugs. Nobody has a right to free drugs. Now you're arguing against yourself.
> > There's no need to punish the creator by not letting them make money off of their creation just because the government was involved, the government is getting plenty out of their investment.
> You're putting words in my mouth.
Which words? Punishment? Ah, the percentage.
> I said the cost of government funded drugs should be the cost of manufacturing plus a percentage for the inventor.
How magnanimous of you. What would you set the percentage at? How would you get companies to manufacture things at cost for you? That's just not how a business survives, and the only people I've ever heard make this kind of argument are people who've never run a business and never will.
> Second, that's not how government funding works. If the public funds a thing, then the public has a right to use that thing.
No, that's not how government funding works, that's how you appear to think it should work in this fantasy you've constructed. Governments often provide funding to private companies that do not create some magical legal right to that company's products.
> If the inventor doesn't like it, then they shouldn't take funding from the government.
I'll repeat, that's not how government funding works. I'm against subsidies in general and in this case but I'd take this dysfunctional way over yours.
> Should the government have not helped fund this drug because now it's expensive?
No, the government should set a reasonable price for the product they funded. A high enough price to fund manufacturing, a low enough price to ensure that people who need the treatment have ready access to it. If the upper bound on price is too low for universal access, that's what subsidies are for.
Instead, we have free money to bootstrap extractive capitalists, at cost and detriment to people who need care.
> No, the government should set a reasonable price for the product they funded.
Do the investors at the company you work at set the prices for the products you produce? That would be strange.
> Instead, we have free money to bootstrap extractive capitalists, at cost and detriment to people who need care.
It's "free" money because the capital costs are high and it's risky. I don't think it's the only or the best way but it is a valid way, but it doesn't remove the right to make a profit.
As to it being "detriment[al]" to the people who need care, they're getting a drug that didn't exist before, right? And this also should (generally) make existing drugs cheaper, right?
I also dream of utopia but when I wake up I have to supply the logic that fills in the gaps else it remains a dream.
If you remove the profit motive then investment falls, new medicines become less likely and lesser in number, and medicines remain higher in cost due to lack of pressure (competition from new drugs, competition from new entrants, new techniques etc).
Altruism, necessary as it is, does not fill that void alone, and it certainly won't be filled by hoping government makes everything "free".
> If you remove the profit motive then investment falls
The last 200 years proven otherwise. All basic research around airplanes, semiconductors, satellites, GPS, GSM, fiber optics, CD/DVD and much much more was almost entirely tax funded.
I’m sorry, but that’s a non sequitur. The alternative is not that the drug wasn’t produced. It is that the drug wasn’t developed by private enterprise.
Please don't give insincere apologies, they're rhetorically weak and pairing insincerity with something that should be sincere isn't a good look.
Which segues nicely to this pairing of public funding and private enterprise. No, if the drug wouldn't be sold for a profit then the incentive to make it wouldn't exist and the funds would not be applied for and the ironic pairing - if it is ironic, which I don't think it is - wouldn't exist either.
Unless we're going to believe that researchers go through the mill of applying for funding and doing research simply to get the funding and stay in badly paid employment?
You get social rewards like titles, getting into vicious personal arguments over personal things, and being able to reject younger researchers’ work in peer review if it would disprove yours.
Can’t displace Chomsky as a famous linguist if he writes a letter to everyone’s dissertation committee if they criticize him.
Academic research is valuable, as is the research done by commercial entities. They're really not comparable in their intent though, and that's a good thing.
It's not an assumption, it was in the example I responded to:
> When he was asked what the device would cost, he cheerily replied "whatever the market will bear."
I also do not need to assume that companies undertaking research are doing it for profit as that is their reason for being companies, and even in the case of research being not directly undertaken for profit, that research - if useful - will go into drugs that are then sold with the intention of making a profit. Not solely, whether cynically or altruistically, the hope will be that the drug is effective.
This is why although I’ve almost got enough money to retire (~20x yearly expenses) but I’ll keep on working for another decade or two. All of these whiz-bang new treatments are going to be expensive. The most expensive medical procedure right now is a heart transplant at about $1M. Then there’s the $10k/mo for a nursing home
The other thing you can do is setup a trust for yourself so that you're broke on paper long before the trust runs out of money. I don't know if it's ethical but it's legal.
Certainly this happens for procedures that should be cheap, and nursing homes are also a huge issue. But in the current discussion it's not clear to me that something like a heart transplant should be cheap. Development of a novel treatment can be very expensive and sometimes involves scarce resources.
The US alone does ~2/3 of worldwide heart transplants, I think there is a tradeoff here. It's also not actually $1 million out of pocket for most people.
Only because you are looking at the country total. Adjusted per capita, US has 7.6 transplants per million population, while eg France has 6.2. Which means, it’s pretty close.
It can't be cheap, and in any high quality medical system apart from US thats not a concern for the patient, ever, at all.
One of those cases where US individualism and utter lack of social thinking (completely unrelated to socialism/communism but many simpler folks fail to distinguish that) screws up needful parts of society
spend a decade of your life to possibly save a few years later? If you are “investing” your time for someone else, perhaps you could just give them your time directly instead?
Yes - that's not unreasonable for a full time care facility for something like dementia or Alzheimer's in the US (it's below what we paid for my grandmothers).
If you're lucky - they have long term care insurance, and that covers most of the expenses for approx 2 to 10 years (depending on how old the insurance is - it's getting harder to find long plans, and they're all getting significantly more expensive as it turns out more folks needed them).
Otherwise... you spend everything, and then your kids pay.
We split my grandmothers down the middle - my mom's had insurance, we covered my dad's.
I am close to someone looking at this now after holding that exact view for a lifetime, what I see them actually doing is delaying and delaying and confronting that, even on their darker days when they are thinking hard about doing it, the logistics of zero-risk-of-survival suicide are pretty terrible.
It's sobering to watch because I, too, hold the view you lay out above, and now watching this, I think I'd better work out my logistics while I'm relatively young and healthy.
I wonder if that is due to the lack of good options for the ending life? I currently feel like I would like to go on my own terms when the time comes, but none of the options available look very appealing! (and many of them can come with legal trouble for anyone who helps).
Even ignoring the fact that human euthanasia is illegal in most of the US, it's rarely that easy. Both of my paternal grandparents lived into their 90s but suffered from mental decline (different forms of dementia) and died as shells of their former selves. If you could have spoke to either of them at the end of their lives but with their full mental capacity, I suspect they would have said that they'd have preferred to die earlier rather than live through that decline... but in reality by the time anyone understood how severe their mental decline would become they were already well past the point that they could have consented to euthanasia.
In theory you could presumably have some kind of system where a person of sound mind could that said, in effect, "if my condition declines beyond _____ then I want to end it," but doing so would be an incredibly touchy subject even if euthanasia was legalized. Unfortunately there is a very real potential for such a directive to by abused by people motivated by greed (gimmie that inheritance) or who simply don't want to deal with an aging relative who needs more help but hasn't reached the point where their euthanasia directive should be triggered.
Assuming forethought one can set up a living trust. I have one. If I can no longer consent then a family member I designated can consent for me. It isn't without risk and requires a lot of trust.
> but doing so would be an incredibly touchy subject even if euthanasia was legalized.
It would, but the alternative is to make people live though this mental decline as we currently do. IMO it would be well worth the risks to be able to ameliorate the end of peoples lives.
My plan is to end my life well before I hit severe mental decline (not “if it gets worse”, with all the ambiguities that entails). If that cuts a few years off then a be it!
It really, really doesnt have to be that complex. If people are religious nuts to believe suicide would bring them to some religion's hell (it won't, since it doesn't exist even if their variant of god(s) would exist), there are tons of ways to pass out rather quickly and not fulfill that criteria, and not bother anybody with the process (various car/train jumpers or suicide-by-cop doers whom I consider utter selfish a-holes).
Walk out to a storm or blizzard not equipped for it. Go fight a bear or lion or crocodile. Go for a swim that you can't come back from. Do some high risk type of adventure that in high age is not even discussed. If you make it, great experience, move to next one.
The list is literally endless and can be done in some form even by quadriplegics. It allows you to plan goodbye and closures, wills etc. The fear and pain and suffering is concentrated into such a tiny sliver of time compared to dying discussed its uncomparable.
It just takes balls to accept that this is it, what mattered for you in life is over, and now its time to think about your closest ones and not yourself. Like a breakup, many will continue living in bad relationship since its a small amount of pain and evil every hour, every day. Instead of standing up and walking off to uncertainty and freedom.
Medicaid will pay for nursing homes (if medically justified) once you run out of money; but the per diem isn't that much. Apparently a lot of nursing homes will commit to accepting medicaid reimbursement for continuing care if you can commit to paying N years first. I've heard usually 2, sometimes 3. If you can swing that, your kids won't have to pay, or they'll pay for incidentals, but not the whole thing. There are homes that just straight up take medicaid, but they review poorly; it's not enough to pay decent staff at reasonable levels, so there you go.
What I've heard about long term care insurance is you can't really buy a plan with useful coverage anymore. The old plans were good as long as the insurer remained solvent, but many didn't.
"Otherwise... you spend everything, and then your kids pay."
That's incorrect. With Medicaid, the recipient is require to spend down their assets to a small amount, then Medicaid will pick up the remainder. The recipient's children aren't on the hook for anything. Of course, they won't receive any inheritance since the estate of the recipient has been drained prior to Medicaid.
This is wrong. Or rather, correct, but only in certain states, and for certain facilities.
IMD over 65 is only offered in some states, and have strict requirements for facilities that accept medicaid (not all that many do near us).
In our case, the waiting time was about 3 years for a room in the facility closest to us. Alternatively, there was an option about 4 hours away.
Worse, both medicaid facilities we looked at were... bad. Frequent complaints about abuse, very high rates of staff turnover, very little stimulation for residents (one was basically a single old tv on the wall in a cinderblock room - it looked basically like prison).
So yes - Medicaid will cover some costs in some cases, but really - the kids end up paying.
My father had long term care insurance. He got Alzheimers, and went into a nursing home, and passed after 3 years. The insurance covered most of nursing home fees.
I did some math on the premiums he'd paid for the insurance, and the payout. It was a break even.
In other words, putting the premiums into an HSA would have financially worked out a lot better.
It's the type of nursing home. If you are in an "assisted living" home, it is less. As a data point, maybe $5800/mo in CA, which includes food and various social programs.
After you file for a drug patent it takes 3-4 years to get approved. You also have to run clinical trials of various sorts, which take years, and then you need widespread marketing campaigns to ensure that doctors are aware of the new treatment. A rough rule of thumb is that it takes about 10 years from the point of filing the patent before you can actually bring the drug to market.
Drug patents are good for 20 years from the filing date, so you have about 10 years to recoup all of your costs, recoup the necessary fraction of your amortized R&D expenses on drugs that didn't go anywhere, and hopefully turn some profit, before your patent expires and generic manufacturers undercut you.
The result is that cutting edge drugs are extremely expensive for the decade or so after they first become available while the patent holder uses their patent-provided monopoly to set prices at the maximum that insurance companies and government health providers will pay. Your link is discussing the period of time after the patent expires and generic manufacturers get into the game, but the drug being discussed here with its $88,000 treatment cost is still in the patent-protected cost-recouping stage, where it's not subject to normal market principles of supply and demand because the supply side is a temporary monopoly.
dodobirdlord's explanation is solid. Basically your link describes "generic" versions of a drug (aka a "brand" drug) with an expired patent. For new drugs they don't have competition like a normal market does because of these patents. To give a summary of the section of the course I linked the market forces for "brand" drugs is the willingness for payers (insurance companies/ governments) to pay.
Chemotherapy for 3-4 months is around $200,000 - $400,000.
You will not see a price reduction, if it doesn't require chemotherapy or significantly reduces the number of rounds of chemotherapy, this drug will cost $150k+ for full treatment.
All of this assumes side effects are better than chemotherapy. Given chemotherapy care plans are some of the most arduous, it will be hard to be worse than chemo.
Price is only slightly related to production costs. It’s much more about all the work that goes into getting something like this from basic science to trials to approval (and all the other drugs that fail along the way).
In the current model, pharma only stays in business by recouping all of the during the patent protected period of any drug that makes it to market.
Generally drugs that cure a condition cost MORE than the pre-existing treatments while under patent protection with no viable competitors. There’s only one source and you’d rather cure the disease with a pill so you’ll pay more.
Market dynamics don’t come into play when there’s only one. If competitors appear or after patents expire it may get cheap, but the cost early on will have no relation at all to production costs.
That's *insane*. Here in Scotland each dose costs the NHS at most a couple of hundred quid, plus about that again to administer. None of that is paid by the patient.
It is a bit like car insurance here, which keeps rising because insurance companies keep edging the cost of a claim upwards (courtesy cars at extortionate rates, repair, ...) because there's no insentive to keep costs down or not profiteer.
With the NHS's buying power for drugs, they can get a little bit nearer a sensible margin from the supplier rather than the insane US costs underwritten by inflationary insurance.
Probably not. That's an average-to-low price for a monoclonal antibody in the US, and many people with chronic (non-cancer) conditions pay that price every few weeks to remain healthy under something like a health-as-a-subscription model.
Some napkin math: Given rectal cancer's rate of survival of 67%, and the small size of the study (18 people), you should see similar results due to random chance every 1350th study.
A cursory search on clinicaltrials.gov and I can find 7131 cancer studies started in 2021 alone. It's therefore not unreasonable for this one to be just a random fluke.
Otherwise redo your napkin math and cursory search to answer, specifically, whether all these cancers disappearing within weeks of dostarlimab treatment could be a fluke. And do not compare this to "rectal cancer's rate of survival", which is irrelevant and a completely different set of (parametrized) statistics, and also do not compare it to the total number of "cancer studies", which was an arbitrary choice and yielded this meaningless conclusion. Even if this kind of analysis was useful, why did you compare against the number of cancer studies, rather than rectal cancer (1910), or dostarlimab (41), or studies with the same staging and genetic pathology? It's meaningless.
I don't believe you're qualified to tell anyone about the significance of this study, and much less dismiss it as a fluke.
The point of that napkin math is not to get an exact prediction, it's to get a order-of-magnitude estimate to see if this study is different from any other of the large amount of "promising drug cures X" articles that never actually turn out to work.
I concede that if a quick remission is extremely rare that does change the outcome, though I don't know how common that it.
Picking 'Total number of "cancer studies"' was not arbitrary. A similar article could have been crated for e.g. "promising drug cures breast cancer" so you need to take all of them into account. Actually probably every study conducted of all high-profile diseases that are likely to wind up on the HN frontpage - in a counterfactual universe we could be discussing a miracle Alzheimer drug or the like.
No, you can't actually figure out whether a cancer therapy worked by counting the number of articles published in a given year. You're focused on this "zero-knowledge" approach because you are completely ignorant about this topic, not because it is actually a more powerful approach.
If you don't even know whether spontaneous remission is rare then you should not be offering an opinion about this. It's not even pertinent because these remissions were clearly not spontaneous, but it should alarm you to have spoken so recklessly about a disease which is essentially fatal. What you're saying amounts to "there's a good chance cancer just goes away on its own". Incidentally, this is also the least amount of math I've ever seen in a napkin math argument.
Pretty sure the base rate you'd want to compare against is either placebo given -> remission or simply spontaneous remission. It appears that spontaneous remission is really quite rare.
> [sponanteous remission of cancer] incidence is roughly one in every 60 000–100 000 cancer patients, but the true figure is unknown (2). Spontaneous regression of colon cancer seems to be particularly rare
If spontaneous remission is super rare it does change the conclusion, yeah.
(Tangentially I think your stats are a little messed up there - you calculated the expected number of people out of 43000 surviving, not the trials returning a false positive. Assuming 0.0016% that chance is astronomically small, so your argument is stronger.)
This napkin math ignores some very significant circumstances.
People who suffer from rectal cancer usually undergo surgery to remove the primary tumor. But those trial patients weren't operated on, their treatment was non-invasive.
How many rectal cancer sufferers who never undergo a surgery survive? I would bet that it is a lot less than 67 per cent.
And this was people with locally advanced rectal cancer. Typically this means the tumor has grown to a considerable size and is already causing symptoms severe enough for people to go to a specialist. I am not a doctor but my understanding is that a placebo in this case would have a 5 year survival rate that is pretty close to 0%.
There should be some kind of award for these kinds of "well actually" comments on HN that lack any kind of intuition for the domain.
Cartoon montage: "By my calculations..." followed by driving a car off a bridge.
Edit: as someone who works in cancer research, I can tell you that your prior for 18/18 locally advanced colorectal cancer patients achieve CRs without surgery should be ~0.
If I understand the article correctly they were excluding patients enrolled in chemo and radiation?
If that's what they mean the survival rate wouldn't be 67% so this would imply a 1349 in 1350 chance the treatment is better than the average treatment?
Other commenters have done a fine job expressing why this napkin math is silly and perhaps in isolated cases this is a good thing, OP probably learned something here
But in aggregate these sorts of comments are annoying as hell on every medical article posted to HN. Now you have to hope a sufficient mass of well-informed commenters is here to rebut them. In the best-case, these comments are simply misguided, but in the worst case it becomes a watering hole for all the antivaxxers and conspiracy theorists on this site to gather
If i put a single coin to the vending machine and get 7 cans instead of 0.98, i surely will try a few times more before reaching the conclusion my coins are magical beans.
Visibly medical research jump so quick to conclusion it's to the millions of news reader to swallow the clickbaits.
relatedly, the only good reason to stop a trial early is that it becomes unethical not to treat the control group because the effect size in the treatment group is so huge. And it does happen, sometimes.
I sometimes wonder if the exhilaration of such a result comes with a twinge of regret that the result could not have been foreseen before the science reached it, and more people given the lifesaving treatment immediately.
But that is the human condition, I guess. Scientific progress and learning brings regrets, often very momentous ones in retrospect.
While I totally get what you mean, I’d guess for scientists, the answer is generally, “no”. Expected outcomes for trials like this are a whole lot less certain to the people doing the work, that than it seems on the outside, so i think it wouldn’t even occur to the scientists that the downside of “withholding” treatment from the tiny (relative to the population) control group comes close to the upside.
Regret, sure, but since we can't change the past that regret should motivate us to work harder to make the present and future better. We're a young species, and part of growing up is looking back with chagrin at how foolish we seem in the light of our new growth and learning.
The number of trials that don't work in humans when it worked in every pre-clinical trial up to that point is enough that it makes sense to be extra cautious.
If this is as effective and reliable as is suggested, this the expense is a cost saving effort. Cancer is an exceptionally expensive disease, at least in the US.
I'm not sure which immunotherapy drug my mother has been receiving, but after being diagnosed with lung cancer nearly two years ago - a tumour roughly the size of a tangerine right in the top corner of one lung, utterly inaccessible by surgery, in absolutely the wrong place to attempt radiotherapy - it's now gone, save for a little bit of scarring and fibrosis where it used to be. The treatment has left her tired and brain-foggy but that's pretty small potatoes to being a chemo zombie, which she absolutely did not want. Although she's in her early 80s she's otherwise in not too bad shape, so that probably helped.
From here on out, it'll be scans every three months or so to make sure it hasn't come back, but her doctor says that if it does come back it'll grow so slowly and weakly that it's just not going to be worth bothering with.
I expect you can imagine the look on Mum's doctor's face when we went in for the most recent scan results - it can't be often an oncologist gets to give someone the best news in the world.
Any idea what cancer she had and what treatment? My mom is currently battling stage 4 metastatic neuroendocrine primary lung cancer atypical carcinoid and being treated with Lutathera, a nuclear injection that targets the somatostatin receptor on the cancer cells and hopefully shrinks, slows, or kills them off. The treatment is 1 injection every 2 months over the course of 8 months. So 4 total injections. She has already been through 4 rounds of chemotherapy and targeted radiation. She has many tumors at this point but the largest sounded similar to your moms, upper left lung, the size of a golf ball. Partially collapsed her left lung. She's being treated at Sloan Kettering in NYC.
There are many articles like this every year. I understand there's no silver bullet for curing cancer, but I am interested in the actual results of new treatments instead of the potential of new treatments, which seems to attract way more headlines.
Is there an overview somewhere of new treatments over the years, and their effect? What is the progress we have made?
As a survivor of colorectal cancer, this is great news, even though the sample size is small and further studies are obviously needed. I'm hoping that by the time my children are at an age where they're at risk, treatments like this will be a well-established standard of care.
Using humans, N = 18. Quick search didn't give any estimate of the chance probability of all going into remission by unrelated reasons, but I imagine it's pretty high compared to the number of small cancer trials run around the world.
Cancer rarely, if ever goes into remission on its own (rectal cancer, specifically). You would never see this happen randomly to everybody in a trial unless there was some external factor.
I don't have a link handy but I have read in the past some cases of trial participants being ejected from a trial because they started prolonged fasting and killed their cancer cells. I suppose that is in line with the external factor you mention.
Along similar lines, I remember reading about a drug/treatment about 15-20 years ago that had similarly extremely positive results, and nothing since. That one worked by reactivating mitochondria in the cancer cells so that they could trigger apoptosis and the cancer would kill itself.
After reading it, my suspicion was confirmed. Yet another mab. Very powerful, but expensive to scale and synthesise. I guess poor people will have to just suck it up and die. We don't have the tech yet to make these cost effective. Big pharma loves this natural barrier of entry though.
Also, don't expect this stuff to be available anytime soon. FDA process is pretty slow, and sometimes political. Maybe if it were effective against Sars-Cov-2, FDA would be willing again to rush it though the door. Still can't wrap my head around how stuff like Molnupiravir made the cut. They just don't have any shame.
-mab drugs really are incredible. I actually take 2 different ones (erenumab and omalizumab), and the results surpassed all my expectations, especially after negative or lacklustre results from many "conventional" medications beforehand.
There were times when aluminium was so expensive that the French emperor dined on an aluminium plate. His guests had to do with gold and silver. Several decades later, aluminium was an everyday material.
I definitely hope that we can come with a cheap method of -mab production. I am almost sure we one day will.
