To summarize: two proposals:
1. Once drugs have passed Phase I trials ... prescribe them
2. repeal ... a provision that requires drug developers to prove a medication's efficacy
Maybe at the time, from 40's to 70's, (1) there were low hanging fruits. It's reasonable to think the discovery process has become harder and (2) we didn't know much about how a fast clinical trial could go wrong [1]
Yes, this was a ridiculous article. In addition, the FDA actually has fast-track approval for drugs in areas with no good treatment and any drug showing exceptional efficacy will make it through the approval process very quickly.
Keep in mind Reason is a libertarian site and approaches every topic with the goal of portraying the modern government always as a roadblock with never any benefit. Every article will be totally one-sided to not mention positive aspects of any government program or agency.
edit: They actually did quickly mention FDA fast-track:
>There have been some moves in the right direction. Between 1992 and 2002, the FDA launched three special programs to allow for faster approval of drugs for certain serious diseases, including cancer. And current FDA Commissioner Scott Gottlieb shows at least some appetite for further reform.
I hear Reason used to be good. My experience with it over the last three years or so is that it's mostly garbage. It's become a lot of narrative confirmation but with little quality reasoning (drink!) or evidence. I don't go there anymore if I can help it.
This law could be terrible, but if that's true, it should be provable without pretending to have data (the safety ratings are the same after non-safety legislation was passed!).
Then there was that one time they published an anti-first amendment screed on the website.
> One proposal, developed by American economist Bartley Madden, is "free-to-choose medicine." Once drugs have passed Phase I trials demonstrating safety, doctors would be able to prescribe them...
>
> More radically, it might be possible to repeal the 1962 Kefauver-Harris amendment to the Federal Food, Drug, and Cosmetic Act, a provision that requires drug developers to prove a medication's efficacy (rather than just its safety) before it can receive FDA approval.
Personally I'd be in favour of letting seriously ill people try whatever they want. However I would not be in favour of allowing companies to charge for drugs which had not yet been proved effective.
Providing drugs for free might give companies more data to help develop (or potentially prove safety, efficacy) but generating revenue here is too open to abuse.
One proposal, developed by American economist Bartley Madden, is "free-to-choose medicine."
Physicians are extremely serious about medical ethics, and lawyers are very conscientious about conflicts of interest. What is wrong with the economic profession, that they talk and talk without any real-world considerations. We saw why Theranos tried to sidestep FDA authority, and with that experience fresh in mind that fellow wants to abolish efficicacy testing. Here, have some homeopathic globuli!
>Providing drugs for free might give companies more data to help develop (or potentially prove safety, efficacy)
It's a nice thought, but you generally can't have patients and doctors opting-in for unproven treatments and expect the resulting data to stand up to any sort of scrutiny. To glean useful data, one would require a really, really large-n study population and clear impacts from use of the drug that are so pronounced they drown out nearly all other confounding factors (e.g. studies on the health impact of cigarettes) -- and expecting an unproven, last-resort type drug to attract a study population this large is just unrealistic.
It's not just that experiments won't work like that, it's the consequences of experimenting on live human beings ... that is where the real problem lies. These companies don't want the freedom to experiment, they already have that. The technical way to state what they want is permission to do stage 2 trials ... and not be responsible for patient outcomes. If their liver gets reabsorbed (which is one of the more common "oops"es for drug testing), they don't want to pay for 50 years of dialysis plus constant treatments. That's what they're asking for.
>>It's a nice thought, but you generally can't have patients and doctors opting-in for unproven treatments and expect the resulting data to stand up to any sort of scrutiny.
It can give much earlier indications of drug efficacy, even if it doesn't provide the proof of Phase 3 compliant studies.
The history of cancer research shows how earlier human experimentation can lead to a much shorter time between a drug being discovered, and it being proven effective enough to become a part of the standard treatmemt protocol. This shorter time to incorporation of an effective drug in standard treatments means survival for hundreds of thousands of people that would have otherwise died.
That the motivations of the parties that would be affected by the loosening of the rules are not all altruistic or even ethical is worth taking into consideration, but it can't be the only priority when crafting regulatory strategy.
A lot of these kind of proposals share the same basic misconception: they assume that once a company identifies a drug candidate, then it's because it works, and the regulatory hurdles it needs to clear to be approved are just bureaucratic paperwork. But the actual evidence of the drug approval process is that said model is completely the opposite of reality. Most drug candidates--around 90%--ultimately fail. Half of all candidates advanced to Phase III (the main efficacy trial) fail. Any serious proposal needs to start from the basis that a drug probably won't work, until proven otherwise.
There is, as it turns out, an existing market segment for drugs that are safety-only-no-efficacy-required approval status. It's the herbal supplement industry, and it makes Big Pharma look like saints in comparison. There's been plenty of exposes showing that many supplement companies can't even be bothered putting the active ingredients in their products.
> Any serious proposal needs to start from the basis that a drug probably won't work, until proven otherwise.
Also any proposal needs to take into account that drug trials kill something like 1-2% of patients and inflict lifelong damage on a further 5-10% of them.
Yes, even the ones "proven" to be safe (in the very short term) to use on normal healthy people.
We've had "free to choose" medicine before, and time and time again there is a screwup where 50 or so people (sometimes more) get subjected to incredible damage or killed because of a confluence of factors (pregnancy is a factor that is particularly famous for messing with drugs in a thousand different ways, as is alcohol, parasites, and certain types of bacteria. But it is very hard to know beforehand, there's even a few drugs that have different effects on different races)
What is the author even talking about, saying there is no progress in cancer therapy? Hanahan doesn't even mention immunology in the "Hallmarks of Cancer" (that's an influential review article from 2000), and less than ten years later it's a huge field of research, with several very powerful drugs in the clinic.
Immunotherapy isn't ignored at all. There are two small-molecule IDO inhibitors in clinical use, I think, some biologics as well, and the efficiency of CAR T-cell therapy is just staggering.
Well, the article is not deliberative, it's polemics. Polemics has a point, it raises awareness, just compare Stallman's attitude to Linus' practicality (it helps if you turn out to be right), but there's sufficient awareness of the libertarian viewpoint already. So I wish they'd just stop, they are tiresome.
First of all, the article mentioned immunotherapy. It'd help if people actually read articles before criticizing them.
Second, the stakes are extremely high when we choose a particular economic path, so extensive discussion about every facet of economics, including the economic effect of regulatory intervention, is warranted. The population is not widely aware of the consequences of regulatory intervention, or even the fact that the economy is becoming more regulated over time (how often do you hear about the "since Reagan, we've tried neoliberalism" trope).
The reason the number of healthcare administrators has increased 3,200 percent since 1970 (compared to an increase of 150 percent in physicians) is the growing number of regulations in healthcare:
Or take the example given from the article, of the cost of clinical trials increasing 12.2 percent per year (inflation-adjusted) in the 1980s, up from 7.3 percent in the 1970s.
These are important enough issues to warrant extensive critical discussion. Libertarians may be wrong (though I don't think they are), but the discussion that has been had around these subjects is not commensurate with the stakes involved, so it's good thing if libertarian polemics attract more attention and discussion to them.
> Cancer deaths have fallen by a total of just 5 percent since 1950. (In comparison, heart disease deaths are a third of what they were then, thanks to innovations like statins, stents, and bypass surgery.)
Not sure if this takes into account x year survival rates.
Don't know why people are downvoting you. I did my postdoc at a biomedical research institute at a prestigious university, and you're 100% right. The work I was doing was related to using ontologies to label anatomical parts. Forget "staring at the sky and imagining a bear", that would be tremendous progress if the cavemen actually agreed on one common word, "bear"!
My understanding is that they won't approve a cancer drug unless it's strictly as or more effective than existing drugs, even if it's efficacy to side effect ratio is more favorable.
The article could have done a post-mortem of the 20-year taxol approval. It sounds obviously wrong, but I'd like to know how it could be done right.
Cancer can be very complex, and treatment based on assumptions can shorten lives and kill fertility when another treatment would have been appropriate.
I think the whole reason why cancer deaths aren't receding as fast as we'd like them to is exactly that heart disease deaths, and violent deaths (anything from murder to suicide to a car accident) are receding quickly. Therefore, people live longer, and get cancer with higher probability.
Right, it would make much more sense to talk about cancer diagnosis or survivability by a certain age, like 50 or 60. By 70-90 most people have been exposed to so many carcinogens the likelihood of some sort of cancer is near guaranteed.
It's not even carcinogens. Cellular decay is a thing. As we age, our genetics start breaking down due to imperfect copying. Cancer is basically just bugs in DNA's software.
> More radically, it might be possible to repeal the 1962 Kefauver-Harris amendment to the Federal Food, Drug, and Cosmetic Act, a provision that requires drug developers to prove a medication's efficacy (rather than just its safety) before it can receive FDA approval. Since this more stringent authorization process was enacted, the average number of new drugs greenlighted per year has dropped by more than half, while the death rate from drug toxicity stayed constant. The additional regulation has produced stagnation, in other words, with no upside in terms of improved safety.
If that were to happen, we can expect that the drug market would become like the supplement market: full of pseudo-science and products that do nothing. Right now, supplement makers are prohibited from making specific medical claims; they can say something like "gives you energy," but they can't say "cures cancer." The only reason they don't is because they legally can't. (And even then they sometimes do, and sometimes get away with it.) If they were suddenly allowed to, we would not get a flood of new drugs from the current pharmaceutical companies. We would get a flood of sugar pills from the current supplement companies.
The "since" part of the paragraph is also a bit of non-sequitur. Before and after the 1962 provision, drug companies had to prove safety, so it's not a surprise the death rate from drug toxicity stayed constant. Proving efficacy is about preventing companies from exploiting the public by selling stuff that has no hope of ever working as advertised.
The blind spot of proposals like this is that they assume good-faith actors acting rationally. They completely ignore bad-faith actors willing to sociopathically exploit people.
>"How can studies be improved so it identifies good/bad drug candidates better and quicker?"
These are not at all hard to identify, but too many people have "bought in" to the bad methods and incorrect results they generated. The main obstacle to progress in medical research is political rather than scientific.
Are you willing to give up cherished beliefs like "tobacco smoke is a strong carcinogen", or "amyloid-beta causes alzheimers", to get cures for diseases?
>>If they were suddenly allowed to, we would not get a flood of new drugs from the current pharmaceutical companies. We would get a flood of sugar pills from the current supplement companies.
We would get a flood of data from human use of the drug, increasing the rate at which efficacy is discovered in drugs.
There may be paths to exploitation mitigation that do far less harm to the rate of good-faith experimentation.
I don't see how one follows from the other. If what you said is true, we would expect the rate at which efficacy in supplements to have already increased, but it has not.
The effect that I think the original article is missing is that sometimes when you radically change the rules in an industry, different actors take over the industry. If drugs don't have to prove efficacy, companies willing to sell drugs with no hope of ever being effective will massively outcompete those that even try a little - it's just massively easier and more profitable.
It follows that more human data increases the rate of discovery, ceteris paribus.
The medical profession would need to hold itself, or be held, to a higher standard than supplement marketers are, for the negative outcomes you describe to not materialize. We can't have a repeat of the surge in opioid prescriptions since the 1990s, where doctors have been compensated by pharmaceuticals for prescribing opioids.
Something a long the lines of Bartley Madden's proposal of requiring doctors to document the results of the use of this class of drugs (those proven safe but not proven effective) in an open access database could go a long way in producing useful information.
More data is not the same as more good data. And there certainly is such a thing as bad data. And I don't trust all doctors enough to rely on them to sift through the real versus the fake. Doctors are not scientists. Further, since drug makers can market directly to consumers, they will start asking for the fake stuff because the fake stuff will make fantastical claims.
You're also side-stepping the issue of over-the-counter drugs. With no efficacy required, we will see a proliferation of sugar pills making specific claims about pain, inflammation, fever suppression, decongestion and allergy reduction that don't require a prescription.
"Doctors are not scientists." This is more of a key insight than most people appreciate. There are some doctors who are scientists (e.g. researcher-clinicians). Having asked many average members of the public "would you consider a doctor to be a scientist?" it's not intuitive for them to answer No.
As someone involved in translating something from the leading edge of research right now, if you speak to straight up practicing Oncologists you have to do a lot of education in terms of bringing them up to speed in the field. We have found researcher-clinicians are easier to speak to and engage with as they are in touch with experimentation and more open minded.
This isn't going to be general physicians doing to the prescribing. It's going to be oncologists, who are generally up to date on the latest developments in oncological drugs.
The idea that enough good data wouldn't be generated from laxening rules, to make it a net benefit for progress on developing/discovering effective new cancer drugs, seems farfetched to me. It requires completely discounting the unpredictability of drug discovery, and the role luck plays in it.
Why would it only be oncologists? Repealing this act would remove the efficacy requirement for the entire pharmaceutical industry, not just cancer treatment.
So you'd be okay with repealing the act only for cancer treatment? My argument is only limited to serious conditions for which specialists become the main point of contact for the patient.
How does this act relate to drugs targeted to specific genetic markers?
I think we're moving into an era when we need to consider that everybody is different, and a lot of cancers are different. This isn't like curing a bacteria, where (mostly) one-size fits all.
I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker, but is safe and will cure cancer for those with the marker?
> I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker
We already do this. A large class of both antipsychotics and antidepressants require certain genes in order to metabolize properly and have the intended effect, instead of just giving a bunch of side effects with no benefit.
These genes are not universal and not evenly distributed; people of certain ethnic backgrounds are dramatically less likely to have the requisite genes, which means that most antipsychotics and antidepressants literally don't work on them.
Yes - if you prove that it is safer than other options for the indicated population, the FDA will approve it with a label indicating it only for that population.
Indications can be as specific as "indicated for tumors with specific mutations"[1] or indicated "prostate cancer when all other options have failed"[2]
Off-label uses of drugs don't need to show efficacy but don't suffer from that problem. Doctors prescribe off-label based on what consensus has shown works even without FDA approved studies.
As a libertarian, Reason annoys the bejesus out of me. As a human, journalists annoy the bejesus out of me.
The real test here is, are drugs more efficacious then prior to the legislation. If not, we need to review it. I'd argue repeal, others would argue replace. I'd look forward to vigorous debate, but first we have to do some actual work to figure out if this legislation is effective. If it is leave it alone. There's probably lots of other stuff we can look at to review, much of which is nothing but drag on the system.
Journalists, of course, have no interest in the truth or doing work that doesn't involve twitter.
You are missing the key point. Supplements are allowed because they are made of "Generally Recognized As Safe (GRAS)" ingredients. New drugs aren't, and that's the point. Experimental drugs are obviously risky.
The big hope for people who suffer from ME/CFS is an off-label use of an existing drug such as Rituximab.
Under the current system, drugs go through phase I trials to make sure that they are safe enough for doctors to prescribe. Then they go through phase II trials to get a feel for dosage and effect size for the intended indication. Then they fail at phase III because they compare poorly with an existing drug for that indication.
What determines whether ME/CFS patients get to try a drug, to see if it does anything for them? Phase I and II results. Fair enough.
But also Phase III. So the efficacy of the drug for a different indication plays a positive roll. If Rituximab were ineffective for leukemia, it would be forbidden to explore it for ME/CFS in a way that might later justify a big trial to check for efficacy. Given the side-effects of Rituximab, that is fair enough, but the law is equally restrictive on all that failed in Phase III. So drugs with mild side-effects that did nothing for the intended indication cannot be explored for ME/CFS.
That is sad. Those who believe that ME/CFS is due to a viral infection would love to try a failed anti-viral. Those who believe that ME/CFS is an auto-immune disease would love to try a failed treatment for Irritable Bowel Syndrome. Meanwhile, researchers tend to stay away from diseases with such unclear etiology.
But the efficacy requirement has worse implications. As wikipedia puts it
> Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment.
So a drug that passes Phase I and Phase II can be eligible or ineligible for off label exploration because of the efficacy of a different drug for a different indication.
Lost my son at 12 years old in 2013 (Bone Cancer) and lost my sister when she was 15 in 1996 (Brain Cancer). The fight for pediatric cancer research funding is worse. If you have a chemo for kids (All of kids cells are growing which makes it much more difficult to fight cancer) it has less side-effects and is effective for adults. If you have a new adult chemo it doesn't mean nothing for Pediatric. We went over 20+ years without one new Chemo till St. Baldrick's funded chemo for Neroblastoma came out a few years ago.
Bone Cancer does have funding, from dog owners. Bone Cancer my son has hasn't had a change in survival rates in 35 years. Fortuitously people have greater hope for a cure for dogs then sick kids and are putting millions into bone cancer research and we hope that once they finally have something we can start the 10 year process of testing for kids.
We wouldn't have done the trial for bone cancer. Reason is that when your in a trial you have to leave the tumor in the body so they can see the effectiveness. Bone cancer is extremely painful and is only curable through surgery. Why would anyone agree to leaving the painful hard tumor in your kids body???
My son had a 15% chance of surviving 5 years when he was diagnosed with bone cancer (It was in his whole left femur and both lungs, bone cancer for some reason grows in your lungs so you have crazy bone cells growing in your lungs). He made it past 4.5 years, but it grew into both legs, his neck, and hip and had countless surgeries, radiation and chemo and it all sucked. That the funding isn't there is a constant thought in your brain at all times. Heck American Cancer Society (Largest on the planet) gave a penny per dollar raised to pediatric cancer research and then cut funding to kids camps and family resources about 7 years ago so they could focus on adult research. They finally agreed to stop using pictures of kids sick on their fund raising efforts. So yeah it is frustrating.
stories like this makes me almost hate life. no kid and parents should suffer this way. I'm really sorry to hear about your loss, I hope you find peace and strength to get through the experience. I could only imagine what you might have went through, I'm sure it must have been real tough.
Surprisingly, if you hang out with kids with cancer you will find them incredibly upbeat and engaged in life (Most of the time. Even people without cancer have our days).
Personally these events have increased my enjoyment of life and I try to not ever take a day for granted. My faith also was increased in the midst of these difficult times.
Now there is still a dent in the door frame where I punched it when I almost dropped him when he was in hospice and needed to go to the bathroom. I leave it there to remind me how mad I got and how much it sucked (We usually remember our past by remembering happy times and forgetting negative times), but for the most part it has made me a and my family better.
You touch on the twisted point about medicine for dogs: there are often lots more treatments for them, at least as many as for humans. But this isnt because of funding. it is because nearly ever human treatmemt was once tested on dogs. And they arent all pets... or even sick. Sometimes the path to human testing leads through dark places.
Uh no, they definitely have specific research facilities for animal treatment. We have a for profit healthcare system, and in that system it goes: Wealthy people > Wealthy peoples pets > poor people.
We had the best medical experience. We had awesome doctors and awesome hospital.
I have to say my son was adopted. He was a dirt poor kid who was neglected and had serious mental health issues due to his enviroment. My son got his femur replaced by one of the best pediatric orthopedic surgeons. His surgeon actually invested the procedure where they replace your femur bone instead of an removing the leg at the hip. We also got to stay at Children's Hospital of Philadelphia (CHOP) and stay at the Ronald McDonald House (This is where it actually was founded).
I figure I will share this video of him since I mentioned his Mental Health issues. My kid was so resilient and he got better. His body didn't get healed but his heart and mind is the biggest miracle I have ever witnessed.
Sorry to hear this. It's pathetic alright. Total prioritization failure.
I'm convinced that if some objective 'progress bar' existed, constantly put in front of the public's mind by media or by government diktat - then a firehose of resources would be put at the disposal of R&D, like X-Prizes for medical enterprises.
Very sorry for your loss. I lost my mother to a similarly deadly cancer two years ago, and this summer my wife was diagnosed at 20 weeks pregnant so both my wife's and daughter's lives were at risk. It is like a curse, having multiple cancers in one's close family.
The HPV Vaccine (and consequent drop in cervical cancer rates - [1]) certainly seems like an improvement. Similarly, the near fanatical application of sunscreen, reduction in cancer causing chemicals, etc. I would have thought would have brought the cancer rate down as well.
HPV vaccine isn't just preventing cancer. I have a rare and potentially fatal condition - HPV warts growing on my vocal cords. I need laser surgery on my vocal cords a few times a year to keep talking, and ultimately to keep breathing.
It's really rare, though... 1.6 adult cases per 100k, and about twice that many child cases (doctors generally believe it's passed during childbirth). Children die from it because it goes undiagnosed, with doctors treating it as bronchitis, when the only actual treatment is specialist surgery.
At any rate, I totally applaud the rise of HPV vaccine. No one should have to deal with this crap.
Bottom line up front: If you have good points, make them. Don't lie to me.
Ways this article misuses statistics and history (lies):
0. Title: When Cancer was Conquerable.
Response: Cancer has never been conquerable. Chemotherapy increased survival rates. Also, cancer is not a single disease.
1. "The first attempt to treat cancer in humans with chemotherapy happened within days of doctors realizing that it reduced the size of tumors in mice."
Response: True, but misleading. Critical question: What treatment is being replaced? When nothing else worked, you might as well try something. Going from 0% effective treatment to 20% effective treatment is huge enough to warrant extreme risks. Going from 50% to 55% may not warrant the same risks.
2. "Cancer deaths have fallen by a total of just 5 percent since 1950."
Response: Everyone will die eventually, some people die of cancer; many more people die with cancer (but not necessarily because of cancer). A better metric would be a combination of things like added years of life due to treatment and quality of life factors.
3. "It is now nearly impossible to conceive of going from a eureka moment to human testing in a few years, much less a few days."
Response: Thank goodness. First, all the easy solutions have been tried. Second, if there is a reasonably, or even partially effective solution in place, the new proposal MUST at least shown to be safe - something that cannot be done in a few days.
4. "To find cures for cancer, we need novel approaches that produce dramatic results. The only way to get them is by lowering barriers to entry."
Response: The only way to reproduce the dramatic results of the past is to stop treating cancer, and then replace the lack of treatment with a new treatment. Also, there is no such thing "the only way". There is "the only thing I thought of" or "this is the way I think will work"
5. "Running a clinical trial now requires getting "protocols" approved."
Response: Among other things, if you just run a study and then try to find some benefit, you will ALWAYS find some benefit.
6. "The problem is clear: Despite tens of billions of dollars every year spent on research, progress in combating cancer has slowed to a snail's pace."
7. "Years ago, a Cato Institute study estimated the loss of life resulting from FDA-related drug delays from 1962 to 1985 in the hundreds of thousands."
Response: Did Cato also do a study to show lives saved by FDA (and IRB, and safety testing) drug cancellations? New drugs are not risk free.
8. "We used to think cancer was conquerable. Today, that idea is often laughed off as utopian. But there are countless reasons to believe that progress has slowed because of organizational and governmental problems, not because the disease is inherently incurable."
Response: We also used to thing we'd have anti-gravity and moon bases by this point. There is also a much deeper understanding of the class of diseases known as cancer.
>>Response: Cancer has never been conquerable. Chemotherapy increased survival rates.
This is a reference to the confidence early researchers had, as a result of the rapid pace of progress. Your literal reading of it is disingenuous.
>>Response: True, but misleading. Critical question: What treatment is being replaced? When nothing else worked, you might as well try something.
An article is limited in the number of caveats it can include. It's pretty harsh to describe a pertinent fact: that human experimentation came much earlier 70 years ago, which in turn resulted in some rapid advances in cancer treatment, as "misleading", because it didn't outline every other contributing factor to the change.
Also, there are cancers today that are 100% fatal. We don't see the rapid time from discovery to human use for drugs used for this class of cancer.
>>Response: Among other things, if you just run a study and then try to find some benefit, you will ALWAYS find some benefit.
This is hyperbole, and in any case, doesn't negate the point about the rising costs of doing human studies.
So you start your comment with:
>>Ways this article misuses statistics and history (lies):
And all I see is you misreading the points made, or disagreeing with the implications of the points made.
If you're going to accuse people of lying, you have a moral responsibility to be more rigorous with your arguments.
The article doesn't include the caveat that the slowdown in progress could be due to the low hanging fruit being picked in the early decades? You're not giving the article a fair or honest review.
On point 5 - for evidence of when the agreed protocol is not followed, with disastrous effects, just look at the TGN1412 trial[1]
Instead of administering the drug to the first patient and waiting to note if there are adverse effects, they were done one after another, and are still suffering ill effects to this day.
Progress is slow because much of the long hanging fruit has been picked
Cancer is much more difficult and complicated than other types of diseases
Clinical trials bypass the FDA but very seldom result in cures or improved survival. It's not like people with advanced cancer are being denied experimental treatments, but the problem is for every success that gets media attention, the vast majority of these treatments do nothing or are even harmful
>"Progress is slow because much of the long hanging fruit has been picked
Cancer is much more difficult and complicated than other types of diseases"
Or maybe the people researching it haven't been doing a very good job and have generated a bunch of irreproducible (even in principle) results:
https://news.ycombinator.com/item?id=17702380
Trying to make sense of a topic when the literature is filled with incorrect facts would be quite difficult and complicated.
What are the options in regular (preventive maintenance ) cancer screening? Cancer is horrible and I feel like by the time we discover the cancer - when it presents itself as a symptom - it can be too late. I realize in general preventive medicine seems to be rarely practiced and medical costs are insane (especially in the US), but is it scientifically feasible to detect most cancers early if proper screening were done on a regular basis?
> Cancer deaths have fallen by a total of just 5 percent since 1950.
This is suuuuper misleading, to the point where I'm thinking that the author has an agenda.
Cancer deaths is the wrong metric to use, since population is always increasing and the proportion of people getting cancer is also changing over time.
You want to look at the cancer death rate instead, from 1991 to 2015 the cancer death rate decreased by 26%. It's also really important to take into account that mortality rates are _vastly_ different across different types of cancers and across genders -- in that same time period, the death rate for males with lung cancer decreased by 45%! [2]
Again, this article is misleading and probably has an agenda behind it. If you want to learn more about the history of cancer treatment, The Emperor of All Maladies is a great book.
The gist of the post was that cancer rates since 1990 have gone down primarily because smoking has declined, not because cancer treatment has improved.
Both the Slatestarcodex article and the links you provided in your comment use deaths per 100,000. In fact, your article reaches a similar conclusion to Scott Alexander, that mortality is declining mainly because of smoking declining.
It touches on that, too. It's also a hard metric to work with because we're getting better at _detecting_ cancers, including more benign and earlier stage ones. I believe the SSC post found that most of the improvement in cancer mortality was more an artifact of detection than actual improvements in care. i.e.: if you look _only_ at equivalent Stage 4 cancers, then the death rate from there hasn't changed much over time.
This is Reason, so of course there is an agenda - the government needs to take it's meddling hands out of our free markets and let us sell whatever drugs to whoever we want!
>In 1971, three decades after Gilman's discovery, the U.S. government declared a "war on cancer." Since then, we have spent nearly $200 billion in federal money on research to defeat the disease. But we haven't gotten much bang for our buck: Cancer deaths have fallen by a total of just 5 percent since 1950. (In comparison, heart disease deaths are a third of what they were then, thanks to innovations like statins, stents, and bypass surgery.)
People live a lot longer than in 1950, which gives them more years to get cancer. This is why you have to report age-diagnosis-specific outcomes and not merely incidence or prevalence.
>why these highly experimental approaches (e.g reprogramming immune cells) can't be done in animals with cancer
They absolutely are, all the time. Animal testing is relatively cheap (esp. for mice) and widespread in biotech. It's generally hard to get an IND approval (step 1 of human testing) without successful animal tests.
Animal models, unfortunately, aren't super effective at predicting human outcomes.
Reason is an unserious publication with an ironic name. The author of this particular article has a financial interest in pushing untested medicine on the suffering. Cancer is a catch-all for a number of different diseases (having a few similarities) that require different treatments. The author chooses to ignore the average age of the population, the size of the population, the diet of the population, and obesity within the population when pulling out statistics. The regulatory framework surrounding medical treatment and drug testing exists BECAUSE people were being harmed by untested medicine.
It’s actually really easy force research to move faster, but to do so people basically must throw caution to the wind, and gamble with the possibility of extremely unpleasant outcomes, on top of also not surviving.
Being less safe is as simple as operating outside the conventional protections that regulatory bodies use, in order to safeguard ethics.
If that’s not your priority, and you want to press your luck, feel free to take your chances, so long as you acknowlege your adoption of the risks that ride along with that decision.
Break the law, in favor of searching places others dare not go. It’s uncharted territory, out where there’s no lifeguard. Maybe it seems timid to shy away from risk in a dire situation, but honestly, push hard enough, and I’m sure enterprising people will ignore their own safety in pursuit of impatience.
“In 1971, Congress passed the National Cancer Act, which established 69 geographically dispersed, NCI-designated cancer research and treatment centers. James Watson—one of the discoverers of the structure of DNA and at the time a member of the National Cancer Advisory Board—objected strenuously to the move. In fact, DeVita in his memoir remembers the Nobel winner calling the cancer centers program "a pile of shit." Watson was fired that day.”
Watson didn’t understand congress rarely approves anything that durant supply pork to a majority of districts.
98 comments
[ 2.4 ms ] story [ 204 ms ] threadHow is this different from Right to Try act? https://edition.cnn.com/2018/05/30/politics/right-to-try-don...
[1] https://en.wikipedia.org/wiki/Thalidomide
edit: They actually did quickly mention FDA fast-track:
>There have been some moves in the right direction. Between 1992 and 2002, the FDA launched three special programs to allow for faster approval of drugs for certain serious diseases, including cancer. And current FDA Commissioner Scott Gottlieb shows at least some appetite for further reform.
This law could be terrible, but if that's true, it should be provable without pretending to have data (the safety ratings are the same after non-safety legislation was passed!).
Then there was that one time they published an anti-first amendment screed on the website.
Reason annoys the bejesus out of me.
Which probably isn't as valuable as it seems. Case in point: look at how AKAO's fast-tracked antibiotic got slammed by the FDA.
Personally I'd be in favour of letting seriously ill people try whatever they want. However I would not be in favour of allowing companies to charge for drugs which had not yet been proved effective.
Providing drugs for free might give companies more data to help develop (or potentially prove safety, efficacy) but generating revenue here is too open to abuse.
Physicians are extremely serious about medical ethics, and lawyers are very conscientious about conflicts of interest. What is wrong with the economic profession, that they talk and talk without any real-world considerations. We saw why Theranos tried to sidestep FDA authority, and with that experience fresh in mind that fellow wants to abolish efficicacy testing. Here, have some homeopathic globuli!
It's a nice thought, but you generally can't have patients and doctors opting-in for unproven treatments and expect the resulting data to stand up to any sort of scrutiny. To glean useful data, one would require a really, really large-n study population and clear impacts from use of the drug that are so pronounced they drown out nearly all other confounding factors (e.g. studies on the health impact of cigarettes) -- and expecting an unproven, last-resort type drug to attract a study population this large is just unrealistic.
It can give much earlier indications of drug efficacy, even if it doesn't provide the proof of Phase 3 compliant studies.
The history of cancer research shows how earlier human experimentation can lead to a much shorter time between a drug being discovered, and it being proven effective enough to become a part of the standard treatmemt protocol. This shorter time to incorporation of an effective drug in standard treatments means survival for hundreds of thousands of people that would have otherwise died.
That the motivations of the parties that would be affected by the loosening of the rules are not all altruistic or even ethical is worth taking into consideration, but it can't be the only priority when crafting regulatory strategy.
There is, as it turns out, an existing market segment for drugs that are safety-only-no-efficacy-required approval status. It's the herbal supplement industry, and it makes Big Pharma look like saints in comparison. There's been plenty of exposes showing that many supplement companies can't even be bothered putting the active ingredients in their products.
Also any proposal needs to take into account that drug trials kill something like 1-2% of patients and inflict lifelong damage on a further 5-10% of them.
Yes, even the ones "proven" to be safe (in the very short term) to use on normal healthy people.
We've had "free to choose" medicine before, and time and time again there is a screwup where 50 or so people (sometimes more) get subjected to incredible damage or killed because of a confluence of factors (pregnancy is a factor that is particularly famous for messing with drugs in a thousand different ways, as is alcohol, parasites, and certain types of bacteria. But it is very hard to know beforehand, there's even a few drugs that have different effects on different races)
Which a lot of holistic doctors have picked up on and some clinics even treat cancer patients in.
Like this clinic in Japan: https://www.saisei-mirai.or.jp who have published several studies and papers on their treatments.
But yeah, why is it being ignored?
Second, the stakes are extremely high when we choose a particular economic path, so extensive discussion about every facet of economics, including the economic effect of regulatory intervention, is warranted. The population is not widely aware of the consequences of regulatory intervention, or even the fact that the economy is becoming more regulated over time (how often do you hear about the "since Reagan, we've tried neoliberalism" trope).
The reason the number of healthcare administrators has increased 3,200 percent since 1970 (compared to an increase of 150 percent in physicians) is the growing number of regulations in healthcare:
https://www.athenahealth.com/insight/expert-forum-rise-and-r...
Or take the example given from the article, of the cost of clinical trials increasing 12.2 percent per year (inflation-adjusted) in the 1980s, up from 7.3 percent in the 1970s.
These are important enough issues to warrant extensive critical discussion. Libertarians may be wrong (though I don't think they are), but the discussion that has been had around these subjects is not commensurate with the stakes involved, so it's good thing if libertarian polemics attract more attention and discussion to them.
“Napster co-founder Sean Parker has donated $250 million for immunotherapy research.”
It was mentioned.
I wonder what's up since.
> Cancer deaths have fallen by a total of just 5 percent since 1950. (In comparison, heart disease deaths are a third of what they were then, thanks to innovations like statins, stents, and bypass surgery.)
Not sure if this takes into account x year survival rates.
There's a saying "live long enough and you'll die of cancer".
Like a bunch of cavemen staring sky and imagining a bear and wondering why some light move around unlike others.
lack of regulation = people make their own choices, take risks, and sometimes suffer the consequences
too much regulation = people die because you killed them
Freedom comes with risk, even at times the risk of death. It is not your place to decide how much risk other people are allowed to take.
Cancer can be very complex, and treatment based on assumptions can shorten lives and kill fertility when another treatment would have been appropriate.
A webcomic author updated their blog about their experience: https://www.erfworld.com/blog/view/60504/rob-lindas-1st-anni...
If that were to happen, we can expect that the drug market would become like the supplement market: full of pseudo-science and products that do nothing. Right now, supplement makers are prohibited from making specific medical claims; they can say something like "gives you energy," but they can't say "cures cancer." The only reason they don't is because they legally can't. (And even then they sometimes do, and sometimes get away with it.) If they were suddenly allowed to, we would not get a flood of new drugs from the current pharmaceutical companies. We would get a flood of sugar pills from the current supplement companies.
The "since" part of the paragraph is also a bit of non-sequitur. Before and after the 1962 provision, drug companies had to prove safety, so it's not a surprise the death rate from drug toxicity stayed constant. Proving efficacy is about preventing companies from exploiting the public by selling stuff that has no hope of ever working as advertised.
The blind spot of proposals like this is that they assume good-faith actors acting rationally. They completely ignore bad-faith actors willing to sociopathically exploit people.
- What is the false negative rate for currently mandated FDA mandated efficacy studies?
- How can studies be improved so it identifies good/bad drug candidates better and quicker?
These are not at all hard to identify, but too many people have "bought in" to the bad methods and incorrect results they generated. The main obstacle to progress in medical research is political rather than scientific.
Are you willing to give up cherished beliefs like "tobacco smoke is a strong carcinogen", or "amyloid-beta causes alzheimers", to get cures for diseases?
We would get a flood of data from human use of the drug, increasing the rate at which efficacy is discovered in drugs.
There may be paths to exploitation mitigation that do far less harm to the rate of good-faith experimentation.
The effect that I think the original article is missing is that sometimes when you radically change the rules in an industry, different actors take over the industry. If drugs don't have to prove efficacy, companies willing to sell drugs with no hope of ever being effective will massively outcompete those that even try a little - it's just massively easier and more profitable.
The medical profession would need to hold itself, or be held, to a higher standard than supplement marketers are, for the negative outcomes you describe to not materialize. We can't have a repeat of the surge in opioid prescriptions since the 1990s, where doctors have been compensated by pharmaceuticals for prescribing opioids.
Something a long the lines of Bartley Madden's proposal of requiring doctors to document the results of the use of this class of drugs (those proven safe but not proven effective) in an open access database could go a long way in producing useful information.
You're also side-stepping the issue of over-the-counter drugs. With no efficacy required, we will see a proliferation of sugar pills making specific claims about pain, inflammation, fever suppression, decongestion and allergy reduction that don't require a prescription.
As someone involved in translating something from the leading edge of research right now, if you speak to straight up practicing Oncologists you have to do a lot of education in terms of bringing them up to speed in the field. We have found researcher-clinicians are easier to speak to and engage with as they are in touch with experimentation and more open minded.
The idea that enough good data wouldn't be generated from laxening rules, to make it a net benefit for progress on developing/discovering effective new cancer drugs, seems farfetched to me. It requires completely discounting the unpredictability of drug discovery, and the role luck plays in it.
I think we're moving into an era when we need to consider that everybody is different, and a lot of cancers are different. This isn't like curing a bacteria, where (mostly) one-size fits all.
I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker, but is safe and will cure cancer for those with the marker?
We already do this. A large class of both antipsychotics and antidepressants require certain genes in order to metabolize properly and have the intended effect, instead of just giving a bunch of side effects with no benefit.
These genes are not universal and not evenly distributed; people of certain ethnic backgrounds are dramatically less likely to have the requisite genes, which means that most antipsychotics and antidepressants literally don't work on them.
Indications can be as specific as "indicated for tumors with specific mutations"[1] or indicated "prostate cancer when all other options have failed"[2]
[1]https://en.wikipedia.org/wiki/Pembrolizumab [2]https://www.fda.gov/drugs/informationondrugs/approveddrugs/u...
The real test here is, are drugs more efficacious then prior to the legislation. If not, we need to review it. I'd argue repeal, others would argue replace. I'd look forward to vigorous debate, but first we have to do some actual work to figure out if this legislation is effective. If it is leave it alone. There's probably lots of other stuff we can look at to review, much of which is nothing but drag on the system.
Journalists, of course, have no interest in the truth or doing work that doesn't involve twitter.
Under the current system, drugs go through phase I trials to make sure that they are safe enough for doctors to prescribe. Then they go through phase II trials to get a feel for dosage and effect size for the intended indication. Then they fail at phase III because they compare poorly with an existing drug for that indication.
What determines whether ME/CFS patients get to try a drug, to see if it does anything for them? Phase I and II results. Fair enough.
But also Phase III. So the efficacy of the drug for a different indication plays a positive roll. If Rituximab were ineffective for leukemia, it would be forbidden to explore it for ME/CFS in a way that might later justify a big trial to check for efficacy. Given the side-effects of Rituximab, that is fair enough, but the law is equally restrictive on all that failed in Phase III. So drugs with mild side-effects that did nothing for the intended indication cannot be explored for ME/CFS.
That is sad. Those who believe that ME/CFS is due to a viral infection would love to try a failed anti-viral. Those who believe that ME/CFS is an auto-immune disease would love to try a failed treatment for Irritable Bowel Syndrome. Meanwhile, researchers tend to stay away from diseases with such unclear etiology.
But the efficacy requirement has worse implications. As wikipedia puts it
> Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment.
So a drug that passes Phase I and Phase II can be eligible or ineligible for off label exploration because of the efficacy of a different drug for a different indication.
Bone Cancer does have funding, from dog owners. Bone Cancer my son has hasn't had a change in survival rates in 35 years. Fortuitously people have greater hope for a cure for dogs then sick kids and are putting millions into bone cancer research and we hope that once they finally have something we can start the 10 year process of testing for kids.
We wouldn't have done the trial for bone cancer. Reason is that when your in a trial you have to leave the tumor in the body so they can see the effectiveness. Bone cancer is extremely painful and is only curable through surgery. Why would anyone agree to leaving the painful hard tumor in your kids body???
My son had a 15% chance of surviving 5 years when he was diagnosed with bone cancer (It was in his whole left femur and both lungs, bone cancer for some reason grows in your lungs so you have crazy bone cells growing in your lungs). He made it past 4.5 years, but it grew into both legs, his neck, and hip and had countless surgeries, radiation and chemo and it all sucked. That the funding isn't there is a constant thought in your brain at all times. Heck American Cancer Society (Largest on the planet) gave a penny per dollar raised to pediatric cancer research and then cut funding to kids camps and family resources about 7 years ago so they could focus on adult research. They finally agreed to stop using pictures of kids sick on their fund raising efforts. So yeah it is frustrating.
Personally these events have increased my enjoyment of life and I try to not ever take a day for granted. My faith also was increased in the midst of these difficult times.
Now there is still a dent in the door frame where I punched it when I almost dropped him when he was in hospice and needed to go to the bathroom. I leave it there to remind me how mad I got and how much it sucked (We usually remember our past by remembering happy times and forgetting negative times), but for the most part it has made me a and my family better.
'Frustrating' doesn't do enough justice, based on your story. I'm terribly sorry for your loss.
https://www.cbsnews.com/news/on-the-horizon-osteosarcoma-how...
I have to say my son was adopted. He was a dirt poor kid who was neglected and had serious mental health issues due to his enviroment. My son got his femur replaced by one of the best pediatric orthopedic surgeons. His surgeon actually invested the procedure where they replace your femur bone instead of an removing the leg at the hip. We also got to stay at Children's Hospital of Philadelphia (CHOP) and stay at the Ronald McDonald House (This is where it actually was founded).
I figure I will share this video of him since I mentioned his Mental Health issues. My kid was so resilient and he got better. His body didn't get healed but his heart and mind is the biggest miracle I have ever witnessed.
https://vimeo.com/65522201
I'm convinced that if some objective 'progress bar' existed, constantly put in front of the public's mind by media or by government diktat - then a firehose of resources would be put at the disposal of R&D, like X-Prizes for medical enterprises.
1 - https://www.sciencealert.com/the-hpv-vaccine-has-halved-cerv...
It's really rare, though... 1.6 adult cases per 100k, and about twice that many child cases (doctors generally believe it's passed during childbirth). Children die from it because it goes undiagnosed, with doctors treating it as bronchitis, when the only actual treatment is specialist surgery.
At any rate, I totally applaud the rise of HPV vaccine. No one should have to deal with this crap.
Ways this article misuses statistics and history (lies):
0. Title: When Cancer was Conquerable.
Response: Cancer has never been conquerable. Chemotherapy increased survival rates. Also, cancer is not a single disease.
1. "The first attempt to treat cancer in humans with chemotherapy happened within days of doctors realizing that it reduced the size of tumors in mice."
Response: True, but misleading. Critical question: What treatment is being replaced? When nothing else worked, you might as well try something. Going from 0% effective treatment to 20% effective treatment is huge enough to warrant extreme risks. Going from 50% to 55% may not warrant the same risks.
2. "Cancer deaths have fallen by a total of just 5 percent since 1950."
Response: Everyone will die eventually, some people die of cancer; many more people die with cancer (but not necessarily because of cancer). A better metric would be a combination of things like added years of life due to treatment and quality of life factors.
3. "It is now nearly impossible to conceive of going from a eureka moment to human testing in a few years, much less a few days."
Response: Thank goodness. First, all the easy solutions have been tried. Second, if there is a reasonably, or even partially effective solution in place, the new proposal MUST at least shown to be safe - something that cannot be done in a few days.
4. "To find cures for cancer, we need novel approaches that produce dramatic results. The only way to get them is by lowering barriers to entry."
Response: The only way to reproduce the dramatic results of the past is to stop treating cancer, and then replace the lack of treatment with a new treatment. Also, there is no such thing "the only way". There is "the only thing I thought of" or "this is the way I think will work"
5. "Running a clinical trial now requires getting "protocols" approved."
Response: Among other things, if you just run a study and then try to find some benefit, you will ALWAYS find some benefit.
6. "The problem is clear: Despite tens of billions of dollars every year spent on research, progress in combating cancer has slowed to a snail's pace."
Response: https://en.wikipedia.org/wiki/Potato_paradox
7. "Years ago, a Cato Institute study estimated the loss of life resulting from FDA-related drug delays from 1962 to 1985 in the hundreds of thousands."
Response: Did Cato also do a study to show lives saved by FDA (and IRB, and safety testing) drug cancellations? New drugs are not risk free.
8. "We used to think cancer was conquerable. Today, that idea is often laughed off as utopian. But there are countless reasons to believe that progress has slowed because of organizational and governmental problems, not because the disease is inherently incurable."
Response: We also used to thing we'd have anti-gravity and moon bases by this point. There is also a much deeper understanding of the class of diseases known as cancer.
>>Response: Cancer has never been conquerable. Chemotherapy increased survival rates.
This is a reference to the confidence early researchers had, as a result of the rapid pace of progress. Your literal reading of it is disingenuous.
>>Response: True, but misleading. Critical question: What treatment is being replaced? When nothing else worked, you might as well try something.
An article is limited in the number of caveats it can include. It's pretty harsh to describe a pertinent fact: that human experimentation came much earlier 70 years ago, which in turn resulted in some rapid advances in cancer treatment, as "misleading", because it didn't outline every other contributing factor to the change.
Also, there are cancers today that are 100% fatal. We don't see the rapid time from discovery to human use for drugs used for this class of cancer.
>>Response: Among other things, if you just run a study and then try to find some benefit, you will ALWAYS find some benefit.
This is hyperbole, and in any case, doesn't negate the point about the rising costs of doing human studies.
So you start your comment with:
>>Ways this article misuses statistics and history (lies):
And all I see is you misreading the points made, or disagreeing with the implications of the points made.
If you're going to accuse people of lying, you have a moral responsibility to be more rigorous with your arguments.
You can't have it both ways. It's either a factual article or a puff piece. (It's a puff piece by the way).
> An article is limited in the number of caveats it can include.
The author does not introduce ANY caveats which get in the way of her points.
> If you're going to accuse people of lying, you have a moral responsibility to be more rigorous with your arguments.
http://wondermark.com/1k62/
Instead of administering the drug to the first patient and waiting to note if there are adverse effects, they were done one after another, and are still suffering ill effects to this day.
[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964774/
Cancer is much more difficult and complicated than other types of diseases
Clinical trials bypass the FDA but very seldom result in cures or improved survival. It's not like people with advanced cancer are being denied experimental treatments, but the problem is for every success that gets media attention, the vast majority of these treatments do nothing or are even harmful
Cancer is much more difficult and complicated than other types of diseases"
Or maybe the people researching it haven't been doing a very good job and have generated a bunch of irreproducible (even in principle) results: https://news.ycombinator.com/item?id=17702380
Trying to make sense of a topic when the literature is filled with incorrect facts would be quite difficult and complicated.
This is suuuuper misleading, to the point where I'm thinking that the author has an agenda.
Cancer deaths is the wrong metric to use, since population is always increasing and the proportion of people getting cancer is also changing over time.
You want to look at the cancer death rate instead, from 1991 to 2015 the cancer death rate decreased by 26%. It's also really important to take into account that mortality rates are _vastly_ different across different types of cancers and across genders -- in that same time period, the death rate for males with lung cancer decreased by 45%! [2]
Again, this article is misleading and probably has an agenda behind it. If you want to learn more about the history of cancer treatment, The Emperor of All Maladies is a great book.
[1] https://www.cancer.org/latest-news/understanding-cancer-deat... [2] https://www.cancer.org/latest-news/facts-and-figures-2018-ra...
http://slatestarcodex.com/2018/08/01/cancer-progress-much-mo...
The gist of the post was that cancer rates since 1990 have gone down primarily because smoking has declined, not because cancer treatment has improved.
Longer lifespans means more people dying of cancer. Something eventually gets you..."natural causes" isn't really a thing.
People live a lot longer than in 1950, which gives them more years to get cancer. This is why you have to report age-diagnosis-specific outcomes and not merely incidence or prevalence.
However, I appreciate the spirit of constant vigilance against the lethargy of bureaucracy, even if I know nothing myself firsthand on this topic.
They absolutely are, all the time. Animal testing is relatively cheap (esp. for mice) and widespread in biotech. It's generally hard to get an IND approval (step 1 of human testing) without successful animal tests.
Animal models, unfortunately, aren't super effective at predicting human outcomes.
Thalidomide is just one example.
Being less safe is as simple as operating outside the conventional protections that regulatory bodies use, in order to safeguard ethics.
If that’s not your priority, and you want to press your luck, feel free to take your chances, so long as you acknowlege your adoption of the risks that ride along with that decision.
Break the law, in favor of searching places others dare not go. It’s uncharted territory, out where there’s no lifeguard. Maybe it seems timid to shy away from risk in a dire situation, but honestly, push hard enough, and I’m sure enterprising people will ignore their own safety in pursuit of impatience.
Watson didn’t understand congress rarely approves anything that durant supply pork to a majority of districts.