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Nearly 400 medical devices, procedures and practices found ineffective in study (sciencealert.com)
274 points by EndXA 33 days ago | hide | past | web | favorite | 143 comments



The study was discussed a few days ago at https://news.ycombinator.com/item?id=20164809


I found this one from the table of reversals to be interesting:

Article: Efficacy of infant simulator programmes to prevent teenage pregnancy: a school-based cluster randomised controlled trial in Western Australia

Summary: The infant simulator is an example of persuasion technology or captology, where the use is intended to prevent teenage pregnancy.26 Their use is widespread in developed countries27 and is expanding into low-income and middle-income countries.28 However, in this study done in Australia, the infant simulator-based VIP program did not reduce teenage pregnancy. In fact, girls in the intervention group (n=1,267) were more likely to experience a birth (8% vs. 4%; HR=1.35; 95% CI=1.06-1.73; p=0.016) or an induced abortion (9% vs. 6%; HR=1.33 (1.00-1.78; p=0.049) than those in the control group (n=1,567) before they reached 20 years of age. This is a reversal of the practice of infant simulator programs to prevent teenage pregnancy.

A school district I contract with purchased some of these "infant simulators" a few years ago. I shared spooky photos of them entombed in foam in their storage cases (evoking visions of racks of "hibernating" astronauts from sci-fi) with my wife. She made a general observation that she thought some fraction of teenage girls would feel encouraged to have a baby after time w/ the infant simulator. Guess there was some truth to that intuition after all.


That would only explain part of the effect. It wouldn't explain why the number of abortions went up by 50%.


- dolls stimulate maternal instinct (child “gets clucky”)

- child gets pregnant

Then

- parents find out, recommend terminating pregnancy

- friends find out, recommend terminating pregnancy

- doctor finds out, recommends terminating pregnancy (“you are not ready for this”)

- unpleasant side effects set in, child decides she is not ready to handle pregnancy, or

- reality sets in, child decides she is not ready to be a mother/wants to finish school

- boyfriend abandons her

Basically increasing the number of pregnancies will necessarily increase the number of abortions.


I can't find the study now, but I read previously that even filling in a questionare asking about tennagers sexual history (or lack of) increases the chance of those teenagers having children and abortions. I assume at that in some level this seeds the idea of sex and babies in a group that might have not had that thought, opportunity or imputus otherwise.


Potentially, the subset of those girls who felt encouraged and then changed their minds.


The majority of every invention / attempt will be wrong in any human pursuit. Just think, 400 useless apps or pieces of software are probably released DAILY to the itunes store. The only difference is the impact, but its still understandable. What if you had to write software that did the following:

* Fixed a bug in an existing "legacy system", deployed remotely without your knowledge. You have no logs or debug information, but you can speculate on cause and try it in small simulated / test environments (e.g. rodents). By introducing this fix you would also be changing the system in unknown ways.

* You only have a vague idea of how the code in the OS for this system works, your fix doesn't even change the code. Your only mechanism of change is injecting some foreign JS into a webform to cause ripple effects on the system for the user, meanwhile the system is setup to try to stop / avoid such "attacks" and will try to undo your fix if it can be detected by the system's "AI".

* if your fix fails in production for even one user, you may lose millions and potentially go jail, that person may die.

* You get one shot to release it to the public, after go-live it basically has to work or everything was for nothing. There is no "push this fix and everything gets better", even one small change is a complete restart (new molecule == new drug).

* If you accidentally release any information about the users, or lose their data, you lose millions and potentially go to jail.

* This software will take 10 years, a handful of scientists, a lab, some lawyers, lobbying, and a few billion dollars to make.

* Every user using your software will be on an entirely unique stack, processing all kinds of data in tandem with your software, and will not follow directions. Some will even have lots of other bugs in the system that are unrelated to your fix.


Have you ever thought that maybe not everything has to be seen through the lens of software? Not trying to be snarky, but it's something I see so often here on HN and it kind of bugs me.


It is much easier to relate to a known quantity than an unknown. I would say the vast majority of people here are either programmers or at least have enough knowledge in programming to relate to it.


Abstract:

> The ability to identify medical reversals [practices that have been found, through randomized controlled trials, to be no better than a prior or lesser standard of care] and other low-value medical practices is an essential prerequisite for efforts to reduce spending on such practices. Through an analysis of more than 3000 randomized controlled trials (RCTs) published in three leading medical journals (the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine), we have identified 396 medical reversals. Most of the studies (92%) were conducted on populations in high-income countries, cardiovascular disease was the most common medical category (20%), and medication was the most common type of intervention (33%).

The original study can be found here: https://doi.org/10.7554/eLife.45183.001


Supplementary File 2 contains the full list of reversals:

https://elifesciences.org/articles/45183/figures#supp2

I don’t know if this is a permalink due to the hash parameter but I’ll try:

https://elifesciences.org/download/aHR0cHM6Ly9jZG4uZWxpZmVzY...


The b64 of that crazy link directs you to https://cdn.elifesciences.org/articles/45183/elife-45183-sup... - maybe slightly more permanent?


I think it's bad policy for the FDA to screen medicines not just for safety but also efficacy. From this study it appears to be frequently unjustified but it gives the drug a seal of approval that has a tendency to replace the judgement of doctors and patients. It's not that the FDA decision makers are corrupt or incompetent. These are wildly complex issues that nobody can get right consistently. Better not to conceal that with centralized decision making.

Modern medicine can't even agree in broad strokes on the proper ratio of macronutrients for humans. We give them too much power when we uncritically accept their judgement on any given treatment. For me, prayer would have no effect. For others it could be a life saving intervention. The efficacy of a particular molecule for a particular patient isn't much easier than that to determine. Therefore decision making should be as decentral and computationally parallel as we can make it.


Efficacy is important as many drugs have significant side effects. If a drug is not going to actually reduce your chance of heart attack or help treat aggressive cancer it's likely not worth the trade-off with side effects.


Not to mention cost, and the opportunity costs that emerge from it.


Part of the opportunity cost being that you could have chosen a more effective treatment if the bar had been set higher. Difficult for patients to be able to correctly determine whether a treatment would actually be good for them. They're not in a good place to decide, for the same reason why lawyers should never represent themselves if possible.


Without some kind of efficacy standard, you could sell water as a cancer cure. That would be very bad for health outcomes.

However, I do agree that it's a difficult topic, in general. Off-label drug uses is one example.


you could sell water as a cancer cure. That would be very bad for health outcomes.

Well, if all you have to do is compare the patient's health outcome of, say, 3 days with water vs. 3 days without, I am sure you could find a very positive correlation between the two treatment paths.


That would be plain false advertising. The FDA doesn't need to get involved in such trivia.

I have no problem with the FDA as a certification agency, whether they're certifying safety or efficacy or both. I do have a problem with their approval being mandatory in order for the product to be sold. If their stamp of approval means anything—if lack of FDA approval implies that a product is unsafe and/or ineffective—then doctors, insurers, and patients will all look for that approval and avoid products without it. The problem is that "safe and effective" is neither necessary nor sufficient to obtain FDA approval.


The lack of safety would affect those who can't afford the "approved" options. :/


Which is more likely to cause an issue, a treatment with no FDA safety approval (but also no history of problems, and possibly safety approval from some other trusted organization) or going without treatment altogether because you can't afford the one with FDA approval and everything else is prohibited?

The existence of uncertified, or just differently certified, options should also put some downward pressure on the prices of the certified options compared to the current monopoly environment. When everyone has to obtain FDA approval there is no incentive to minimize the cost and plenty of reason for established incumbents to make approval as expensive as possible to lock out any potential competition. You can always push for "more safety" above and beyond the level of risk reasonable people would be willing to accept.


Mixing up cross-approval (from let's say the EU's EMA) with no history is very dangerous. Exactly because snake fucking oil salesfolk rely on the latter.

Downward pressure is nice from unapproved/unknown stuff, but any kind of price stratification inevitably leads to harm for those who are at risk the most.

People already order generics on "ebay" and a lot of those shipments are seized at customs, etc.

We know why prices are high in the US. And that's not because the need to go through FDA approved trials, but because of patents and because every other developed market got their shit together and negotiates in bulk with suppliers. (Thus the US market is what pays for most of R&D.)

> FDA approval there is no incentive to minimize the cost

Do you mean the cost of going through the approvals? I think it should be largely subsidized (and ratio should be computed from a reputation score of the requester - of course using the lower bound of the Wilson score interval, or something similarly fast converging).

> established incumbents to make approval as expensive as possible

True. But there are quite a lot of newcomers. VC money is pouring into medical tech. (Though usually small promising research projects [and sometimes the labs themselves too] are bought up wholesale by bigger companies that then do the preclinical and clinical trials and the FDA approval.) This of course incentivizes incumbents to consolidate.

Keeping the approval sane is largely the job of watchdog organizations (NGOs, other civil advocacy groups, expert groups). Of course filtering the lobbyist bullshit should be the job of everyone's beloved dear leaders. The incentives are not stacked in the common man's favor, as we already know it for some time.

Pushing for safety is of course the usual think of the children argument, but I'm not pushing for more. I'm pushing for the same amount that is currently there.

Furthermore, the FDA costs are almost negligible compared to the development cost of new drugs. (Seriously, it's less than one percent.) And running clinical trials themselves cost a lot of money. Which is something that cannot be simply avoided. Because human biology is very complex, and even with these trials getting the signal from the noise is not easy. Just look at the mess in psychiatry ( https://slatestarcodex.com/2019/05/07/5-httlpr-a-pointed-rev... how basically targeting one gene is [almost?] completely uselss)


> The efficacy of a particular molecule for a particular patient isn't much easier than that to determine.

How do you handle situations where the provider doesn’t know/care which is best either and just chooses the intervention that was the most heavily marketed to them?

Why do we see new patent drugs replace the “old and boring” generics without any proven efficacy benefit?


You make public health care with fixed prices to contain the capitalism incentive. Worked for us in france: hospitals get pressure from the state and must justify their refundable expenses.

It's not perfect, there are still abuses, but it's nowhere the circus we see in the US.


How about outpatient prescriptions? Does a GP (or group thereof) get a budget of expenditures on prescriptions that they have to stay within?


I never heard about it.


> For me, prayer would have no effect. For others it could be a life saving intervention.

In the same vein, I often get to read about an emerging approach called precision medicine.

Precision Medicine refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease, in the biology or prognosis of those diseases they may develop, or in their response to a specific treatment [1]

[1] https://en.wikipedia.org/wiki/Precision_medicine


Even computationally parallel algorithms hopefully have a centralization point where the compulation completes. What's the equivalent for whether or not a drug is more effective than a sugar pill, given countless edge cases? I could imagine a case where a drug that was never effective is widely distributed before being calculated to be no more effective than placebo. In the meantime, such a widely distributed drug could cause significant harm as it is selected over medication with actual efficiacy or effective drugs avoided due to the side effects of the ineffective one.


It seems wrong to judge based on the number of false positives without weighing agianst all the snake oil they keep out.


Also sometimes a medicine's most important uses end up being off-label anyways. E.g. http://nielsenhayden.com/makinglight/archives/007140.html


Typically the efficacy stamp does come with whatever caveats came up during FDA approval - for example, my SSRIs came with two sheets of double sided paper listing in excruciating detail the potential side effects, and reminding me on every page that the pills may just make me want to kill myself so watch out for that.

SSRIs being top of the list of drugs that "sometimes work sometimes don't" I think are a good example of why the FDA rubber stamping efficacy are still good. I'm not convinced I'd had those sheets of paper if drug makers had the run of the market.

I've never actually seen evidence that a "free market" (i.e. drug market with no FDA) results in a better world for consumers, unilaterally.


“Therefore decision making should be as decentral and computationally parallel as we can make ”

This may work if the decentralized decisions were made based on results. But they are often made based on profits and there is a lot of money to be made in doing useless therapies.


Please, let's not kid ourselves about what actually is life saving intervention for a person. It downplays the need for funding and we're already dealing with a lot of suicides per day.


Not screening for efficacy will result in both legitimate cancer medication and homeopathic medicine having an FDA stamp of approval.

Nothing is stopping decentralized decision making, you just need to market whatever non-effective but safe remedy you're selling as a food supplement, a tea or whatever. You just can't advertise that it's a drug.


> Nothing is stopping decentralized decision making, you just need to market whatever non-effective but safe remedy you're selling as a food supplement a tea or whatever. You just can't advertise that it's a drug.

Unfortunately, this is false. The FDA will still intervene in situations where it doesn't like what you're doing even if you don't advertise your work as a drug, medical procedure, or as having any particular efficacy.

https://www.technologyreview.com/s/603530/a-biohackers-plan-...

On another note, see the sensor pads story here: http://www.fdareview.org/devices.shtml

"We rarely get to try products that the FDA fails to approve, and we never get to try products that are never brought into existence because FDA rules and regulations have made research and development uneconomic. As a result, the public remains ignorant of the true costs of FDA power."


The story you've linked to is where the FDA shut down some private individual selling genetically modified dogs to the public.

But yes, the FDA aren't complete morons. If you're selling genetically modified dogs you're obviously selling the results of an unapproved medical procedure to the public, even if all you say about it is that you're selling fluffy friends to the public.

The second story you've linked to is one where someone was clearly trying to sell a replacement for breast examinations to the public.

I've never heard about the "sensor pad" before, and there's probably a good case to me made for such a device being more beneficial than not, and that the FDA made a mistake etc.

But I think their process is more sound than not in demanding clinical trials of these sorts of products. This is because in practice people will use them as a replacement for going to their physician, so having some DYI breast cancer scanning kit doesn't just need to be harmless in isolation. You also need to consider the increased death rate from people not going to their doctor for an examination as a result.


What kind of bizarre definition of the term "medical procedure" would exclude using CRISPR gene editing to get rid of an inherited disease?


Well, the one that says medical procedures are only practiced on people.... and that embryo editing is not editing a person. But anyway, we really do need a way for people to let themselves opt out of the FDA's regulatory regime for all sorts of reasons- chronic pain, euthanasia, pick your poison there's thousands.


>Unfortunately, this is false. The FDA will still intervene in situations where it doesn't like what you're doing even if you don't advertise your work as a drug, medical procedure, or as having any particular efficacy.

This is completely false. Proof: homeopathy and chiropractic are very popular and still on the market.


You lost me when you made the assertion that the FDA isn’t corrupt.


Is this a general assertion that "government" is corrupt, or do you have any specific assertions? Can you describe how you think drugs are approved and at what stage the "corrupt" FDA manifests itself?


Most comments here are only focusing on medical devices; this is about the practice of medicine, not shitty companies!

In dentistry/endodontics it was believed for a long time that installing a post helped keep a crown and tooth intact for longer. But long term studies showed posts can actually reduce longevity. In another case, a study showed that a common type of knee surgery for pain is actually less helpful than a placebo surgery.

The overarching problem is that it's (currently) very hard to evaluate the real effect of practicing medicine on large swaths of the population, and then using those results to change what doctors do. By getting doctors into a continuous improvement cycle, we could identify costly, useless practices, and improve health.



Remember, in research it is easy to conclude that some treatment does no good -- just do sloppy statistics. E.g., collect some data, flip a coin, and report the results of the coin flip. That will work because the coin flip is, in probability, independent of everything else including the data and treatment. Well that's not the only way to do sloppy statistics -- just pick some measures that are relevant but not very good. And use a small sample size.

E.g., there are some reports on how much data was needed by the Large Hadron Collider (LHC) to conclude that the Higgs Boson DOES exist -- the amount of data needed was beyond belief. Sooooo, anytime well short of that much data they could have conluded that the Higgs did not exist, that is, so far their data failed to show that it DID exist. Same for any treatment: If don't collect enough data, use poor measures, let the data get corrupted, etc., i.e., do sloppy work, then will fail to find where the treatment did work and conclude that it didn't.


I do remember watching a documentary about medical devices where it describes a FDA loophole; if the device you are trying to introduce is similar to a previous already approved product then the scientific rigor involved is significantly less. I wonder if this has something to do with it.


I wonder how many of these are still covered by insurance companies. You'd think they're in ideal (data collection) position to raise questions about what works and what doesn't. Certainly, the insurance cos have more incentive to raise red flags than Big Pharma.


upvoted this, but what happens with conflicts of interest? for example, what if insurance companies insure both patients (to cover medical expenses) and doctors (to cover malpractice lawsuit costs)? insurance company houses and systems are typically set up such that the house will statistically win out (a supposed small tax that pays for running the paper work, and manpower within an insurance company). In such a setting, where insurance companies insure both doctors and patients, the net motivation is no longer defending what works, but increasing throughput of interactions...


Challenging chemo: https://www.icnr.com/articles/ischemotherapyeffective.html

Australia has a study that's pretty damning. Is that one of these practices listed?


the website you linked reads like homeopathic conspiratorial junk. I would be wary of anything they cite


The papers cited (eg Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol). 2004;16(8):549-60.) have been instrumental in removing Chemotherapy as the defacto treatment of many cancers in Australia. The science is definitive insofar as the inefficacy of the treatment.

The pharmacological industry resistance to these findings is unsurprising.


Here's information about the Cancer Drugs Fund which was used in England to provide access to newer forms of chemo.

Most of it didn't work, and caused severe side effects.

This is from the British Medical Association: https://www.bmj.com/content/357/bmj.j2097

This is from the Royal Society of Medicine: https://journals.sagepub.com/doi/full/10.1177/01410768187968...


It's hard to see this headline as something other than a result of The Irreproducibility Crisis.


Can anyone comment on the validity of this publication? I'm sceptical towards the site given it's "flashy" title and I'm not well enough schooled in distinguishing good vs. bad publications.


Everyone yelling about how the FDA is corrupt or should only screen for safety are completely ignorant of history and basic facts.

Medicine is not like trying out a new coding framework - in some cases, like cancer:

i) There is no ability to "try it out for your self" - you are either all in or not

ii) There are extreme risks to taking the drug (most cancer drugs are actually somewhat to extreme toxic...just less toxic than cancer)

iii) You only get a few tries (since, you know, cancer will kill you).

iv) People are very desperate and will try anything

v) Data sharing is very very hard given the sensitivity of the information (patient data) - making it effectively impossible to have an open data exchange. (This is also due to the billions of dollars at stake on the pharma side).

Try designing a system to overcome those challenges...and you will likely end up with a central governing body that looks like the FDA. Anything else you are going to get way way more drugs that don't work, which waste time and money and kill people, which endanger patient privacy, or which are not satisfactory to pharma or, ...

The fact is, the FDA is full of many of the smartest and hardest working doctors and scientists in all of medicine. They take their jobs extremely seriously. They are far more careful and rigorous than most academic or even pharma-level researchers.

Do they get it wrong? Yes, occasionally. Not frequently. Occasionally. But that also, is science. The FDA follows rigorous statistical procedures, but even p<0.05 (or <0.001) still means false positives can happen.


This. Having been through the FDA process myself (though we didn't make it to NDA, sob) I have to say that dealing with the Agency was great. Tedious, but great, and nothing seemed stupid except some trivialities at the margin (e.g. certain formatting issues).

Honestly the worst parts of dealing with them are direct consequences of people trying to game the system. We went out of our way to make sure nothing we did could give that impression and got excellent guidance and response.


Same.

Been through that process with a couple products from a medical imaging software startup. Extreme professionalism and competence was the lasting impression I got from my time interacting with them. We were making software that could be used in oncology for diagnosis, analysis, and treatment planning, so yeah, we got the regulatory proctology exam. But I wasn't annoyed at all. They were highly competent people who took their duty to protect the public from me seriously.

I took no offense at all.


Sounds interesting! Which startup?


>Do they get it wrong? Yes, occasionally. Not frequently. Occasionally. But that also, is science. The FDA follows rigorous statistical procedures, but even p<0.05 (or <0.001) still means false positives can happen.

The issue is that there is a huge lack of transparency. When a third of the studies involved in approval of anti-depressants were withheld from the public [0] and even some withheld at the insistence of the FDA [1], what good do low P-values do?

Hard to trust the science when you're not even allowed to review the papers for yourself.

[0]: https://www.nytimes.com/2008/01/17/health/17depress.html

[1]: http://www.washingtonpost.com/wp-dyn/articles/A9802-2004Sep9...


Well, current medical research is not really science, more of a sort of office politics with added prestige and financial incentive.

Actually you can read all the papers you want, you have no guarantee that what's on paper is what happened. Academic and industrial misconduct and epidemiological ignorance are so prevalent in the field that it's more akin to a religious cult.

No, unfortunately I'm not being pessimistic. This is also the case for the FDA people. They can't know, even by doing good work and to a very large extent, whether something will prove harmful or useful.


>you have no guarantee that what's on paper is what happened....

Can't speak for others, but we were deathly afraid of submitting anything dependent on papers that we had not verified ourselves to 100% satisfaction. This actually held us up a lot, but it was safer than taking a chance that you would get it by those people at the FDA. Now of course, we were making software, and when you deal with computer science research, there are a lot of BS papers out there. I remember reading through papers on ray tracing, which had supposedly been peer reviewed, but were presenting arithmetic that was entirely incorrect. Literally every paper we found on this particular algorithm was riddled with almost identical mathematical errors. It was crazy. (I would say that computer scientists have got to be the worst mathematicians I've seen during my time in the sciences.) In any case. I knew that one of the people we were dealing with was a pretty good math guy. Yeah, we decided not to chance it.

Having bogus research out there is one thing, getting lucky enough to slip it by the FDA is something entirely different. Don't mistake those two things for the same issue, it could cost your company. Or worse, if you do manage to slip it by the FDA, it could cost your freedom when your bass ackwards ortho normal basis calculation switches left and right, and the surgeon goes in after the wrong kidney.


During my MSc, I was implementing, validating, and comparing multiple numerical methods for a certain field of Aeroacoustics. Most (peer-reviewed!) papers had errors, some glaring, some subtle. The cynic in me thought those were done on purpose so that results were harder to reproduce.

There was one specific signal change (a + to a - in an equation) that took me almost a month of hitting my head against a wall to figure out...


Yeah, people need to learn that just because it's published doesn't mean it correct. The problem worsens when people just link papers they don't understand when arguing online.


Having worked closely with FDA, I've been very impressed by the people there and how thoughtful they are despite the pressure they're under and the almost complete lack of good software tooling due to the sensitivity, regulatory requirements, and complexity and specialization of the data. Most of the medical officers there could easily be a very successful (and much higher paid) private physician or a pharma researcher somewhere but choose to remain at FDA.

On one point people are making specifically -- unlinking safety with efficacy is really tough -- an immunooncology product that causes serious AEs/hospitalizations in a quarter of the population and costs $250k and only extends life by 6 months may be approved because the alternative is almost certain mortality; whereas another drug may not be approved simply because it increases bleeding risk in a small percentage of people because there are good alternatives already.


With respect to cancer drugs, while generally no one can be prescribed medication that has not passed clinical trials, in the case of terminal patients who could potentially be saved by a drug currently in trials, there is a system for allowing them access to the medication.

It's called "Expanded Access" (also known as "Compassionate Use") https://www.fda.gov/news-events/public-health-focus/expanded...

The other reason why data sharing is hard is because it costs on average over $1,000,000,000 (1 billion USD) and 10 years of time to whittle over 10,000 drug candidates into a single new FDA approved NME (new molecular entity).

If you spent a billion dollars and a decade on a project, you will consider the data you collected to be a trade secret and would protect it with everything you can, because you have to now take this drug to market and make up the billion you spent making this drug. If you simply shared all your results, foreign competitors will simply copy your work without paying you, and will then offer your product without the cost of R&D and regulation built in: AKA they will charge 1/10 or less than you and you will struggle to profit anywhere they are in the market.


This is a good argument for government funded R&D, and government owned drugs.

They cost a ton of money and take forever to create, so the product becomes very expensive, and rights to it are owned by the creating company. The government empowers a body to regulate the flow of new drugs on the market, and once the drug meets regulatory requirements, the government - in many cases - pays on behalf of the patient.

A company is interested in making a profit on their time investment, whereas the government could be content to break even (for the good of their citizens).

If the government instead paid a company to do the R&D, maybe even providing access to approved facilities where the work is to be done, the government could then retain ownership of that product and then create agreements with drug manufacturers to produce those drugs.

This solves a couple of problems, like sole producers of a product arbitrarily increasing prices (it is expensive and time consuming to set up production for a new drug, even if it is off patent), as well as supply issues (I don't think right now the FDA has any rules saying a drug company must be able to supply a certain amount of a drug to get their license to distribute).


A good argument against government funded R&D is that several of our modern medical challenges have been deeply embroiled in political debates.

AIDS/HIV(originaly called GRID) was originally considered a punishment for gay men who were seen in the 80's as being immoral and sinful by the establishment. Government-funded R&D for AIDS drugs would have been unlikely for decades.

Another example is hormonal birth control. Birth control in general is a huge political football with portions of the establishment wanting no access to birth control at all. If R&D were government funded it's possible for these people to prevent access simply by making funding of certain lines of research illegal.

I think you have to look beyond the price of treatment to really see the benefit of a healthy private enterprise here. There are still a ton of ways that government contributes to new treatments, like grant funding for basic research and development. But I can see your proposed future becoming a dystopia, where whoever is in power in government makes it illegal to sell certain patented drugs to their particular underclass of the week.


> If you spent a billion dollars and a decade on a project, you will consider the data you collected to be a trade secret and would protect it with everything you can, because you have to now take this drug to market and make up the billion you spent making this drug.

You would also be heavily incentivized to make sure the numbers show that your drug is effective, with very limited side effects..


You can try to fudge your data but the FDA is the most rigorous science based regulator in America and possibly the world.

And, the FDA monitoring of drugs requires more than Phase 1-3 clinical trials (which cost hundreds of millions of dollars to produce some of the most rigorous science in human history), but they also do post-release data analysis (so called Phase 4), and have even recently pulled drugs which are not meeting the Phase 2 and 3 standards for safety and efficacy over existing treatments (not efficacy over placebo, the results must show efficacy also over existing drugs).

Not to mention, the FDA fines of pharma corporations are some of the largest fines in American history.

So with the FDA you have

* A regulator using science forcing big business to spend 10 years creating scientific evidence that their product is safe and effective. No other industry on the planet has these requirements.

* A regulator using market data to actively govern products and pull products which aren't safe and effect (pretty normal)

* A regulator assessing multi-billion dollar fines pretty regularly https://en.wikipedia.org/wiki/List_of_largest_pharmaceutical...

You might find this surprising but pharmaceuticals is a money losing industry in the long term. Most of these companies are looking pretty bad, they're spinning off any division which could potentially be profitable (biologics, medical devices maybe) but your average business of finding new drugs? It's not profitable, the regulation is so intense and the work is so hard and competition which ignores intellectual property is so damaging that it's very likely most major pharma companies will go bankrupt in the coming decades.

When you compare how much science the FDA makes drug companies do to any other industry, food, finance, supplements, makeup, cars, houses, anything at all... nothing else compares. A forensic audit is nothing compared to a Phase 3 clinical trial. Far less goes into proving a car is safe than a drug. Etc.

The FDA is doing incredible scientific work with an extremely thin budget.


Thank you for this. So often we rip on government agencies from our perch on...Hacker News, when we really have no idea what's going on.

We do work with the Government in a different context, and I've found nothing but professionalism and deep expertise. In fact the people I've met in the agencies we're working with are some of the smartest I've encountered in my entire career.


>often we rip on government agencies from our perch on...Hacker News, when we really have no idea what's going on.

In a single department, we don't know.

As a whole, it's been shown over and over that like any organization, government becomes corrupt.

Between defense and universities, I've heard depressing ancedotes as well.

It's lucky and temporary you had a good experience.


That seems like a pretty cynical perspective to me. Like if Edison had said "it's been shown over and over that electric light bulbs don't work" after the first couple hundred experiments didn't pan out.


In every country, in every world, in every decade of humanity, in every department.

But this time will be different.

Very interesting take.


You clearly have never dealt with people from local jurisdictions, such as from the local city government or county governments, and even up to the state.

I hate to say it, but every one of these folks I have encountered falls into two categories: 1. Recent college graduates who don't know much if anything, 2. People who have worked a government job for a long time but have little intellectual capacity to understand complex subjects.


I deal with people in local, city, county, and state governments all the time.

Haven't met many recent college graduates, as they don't usually have the experience to land a government job. Have met a few old-timers. But otherwise almost all of them were efficient, helpful, and good at their jobs. In the specialized departments, they definitely had the intellectual capacity to understand complex subjects and could have earned significantly more money in private practice if they wanted to waste their lives in a rat race.


I guess I need to find a job in your area then, because my experiences here are the pits.


Also it’s important to understand the context that medicine wasn’t originally “scientific “ for all the reasons you are touching on.

Historically treatments were based on some theory of how the body works, and a plausible intervention either based job that model, or based on tradition and anecdotal experience.

As people tried to implement more empiricism it hits all the difficulties you mention and others ... it’s an extremely difficult ugly challenge.

We should have lots of medical reversals. It means we are slowly getting better. Probably things could move faster if there was some giant anonymized database of every patient treatment, with documentation of symptoms, intervention, and outcome.

There are so many reasons why that is impractical, I’m astonished we are making the progress we are.


> are completely ignorant of history and basic facts

Sam Peltzman's "Regulation of Pharmaceutical Innovation" does an evaluation of this based on statistics, and concludes that the efficacy requirements are a net negative.

It's not about the FDA scientists being incompetent. It's about the increase in cost is so large that far fewer new treatments are even attempted. Conditions that affect a smaller number of people are simply not worth finding a treatment for.


>Data sharing is very very hard given the sensitivity of the information (patient data) - making it effectively impossible to have an open data exchange. (This is also due to the billions of dollars at stake on the pharma side).

There is promising work going on in this area to allow the sharing of models while maintaining privacy. (Differential privacy, homomorphic encryption, multi-party computation, etc.)


It's always worthwhile to learn the history of an organisation. That tells you a lot about it's culture.

https://en.wikipedia.org/wiki/History_of_the_Food_and_Drug_A...


This is true, but there may be moderate reforms that would work. Could drugs approved by European regulators be allowed without FDA approval? Which regulators do a better job?


> Could drugs approved by European regulators be allowed without FDA approval?

Why should they be? It's not like European regulators have a better track record than the FDA here.


Well, Propranolol was available in Europe for its main indication about a decade earlier than it was allowed in the US saving 10,000s of lives. European drug regulation encourages competition in ways that provide for about a dozen EpiPen equivalents rather than just one provider that can jack up its price to $1000. You can buy sunscreen that blocks both UVA and UVB in Europe, though the FDA is thinking about maybe allowing those sunscreens in the US soon. They did miss Thalidomide, though.


> European drug regulation encourages competition in ways that provide for about a dozen EpiPen equivalents rather than just one provider that can jack up its price to $1000.

This has literally nothing to do with FDA approval of NMEs.


No, but it is a reason you might want to be able to buy drugs imported from Europe.


> No, but it is a reason you might want to be able to buy drugs imported from Europe.

Which is illegal in itself, for reasons that have nothing to do with FDA approval or the issues relevant to this article.


As long as they're not worse, it could result in more approved drugs.


>to actively seek out independent, governmental and non-conflicted clinical research

does this mean private sector pharma studies are to blame?


I read the original study. I have a few thoughts. My partner is a physician and I am an AI researcher working in medicine. I think a lot about doctors as machine learning models, and RCT results like loss terms in a complicated objective function.

What is the best learning rate for updating physicians (our models) from the results of RCT's (part of our loss)?

The authors reviewed all articles in three journals from (generally) between 2003-2017. They didn't, afaict (please point me if they did), review the time-to-correction (if any correction has been made). It takes some time before the results of an RCT end up in established practice. I'm actually surprised it's so small in many cases.

It's not like there's a database where the results of every RCT are immediately updated and the physician model is retrained overnight on the new data.

Even if there were, imagine if the learning rate (so to speak) were so high that every discipline immediately changed their published best practices on the basis of a single RCT?

Here's a cautionary paragraph from one of the excellent reversal studies they use:

Several limitations of the study warrant discussion. First, because we enrolled only 26% of eligible patients, our findings must be generalized cautiously. The most frequent reason that patients declined enrollment was a strong preference for one treatment or the other. Since patients' preferences may be associated with treatment outcome, our trial may be vulnerable to selection bias. Participating surgeons may not have referred potentially eligible patients because they were uncomfortable randomly assigning these patients to treatment; this form of selective enrollment may also create bias.26 Second, because the trial was conducted in academic referral centers, the findings should be generalized carefully to community settings. Third, we did not formally assess the fidelity of the physical therapists or surgeons to the standard intervention protocols. Finally, our study was not blinded, since our investigative group did not consider a sham comparison group feasible. [0]

I'm less concerned about RCT to Best Practice time than from Best Practice to Typical Physician Practice time. There is a cascaded model connected to the 'complex RCT loss' and it's discipline published practice down to individual physician treating patients. Compressing the time from RCT to individual physician is fraught with difficulties, but could be improved.

Finally, RCT is the gold standard, but it's not perfect and it doesn't always clearly translate to the individual physician's model of practice. Many best practices weren't established from RCT's either.

And an inconclusive result from an RCT is not the same thing as proving that there's no difference in outcomes, but a proper statistician can chime in there.

[0]https://www.nejm.org/doi/full/10.1056/NEJMoa1301408


[flagged]


If you keep posting unsubstantive comments or flamebait to HN, we will ban you.

https://news.ycombinator.com/newsguidelines.html


Banning someone for expressing opinions you disagree with falls in line with some very bad history.

My comment wasnt unsubstantive by any definition of the word. There are countless examples of the govt doing things to lose trust and that is the root cause of many of societies issues.

Banning people from a forum for expressing that thought seems counter to the guidelines you post.


The issue isn't agreeing or disagreeing. I don't have the energy to agree or disagree with most comments that get posted here. If that sounds odd, imagine how weary you'd be after doing this thirty thousand times, which apparently I have by now.

The comment was against the site guidelines. Provocative, grandiose claims on controversial topics are flamebait.


You pay hardly anything to the agency -- their fees are a rounding error compared to all your other costs. And while it's valuable for some jobs to have on your resume that you used to work there, so many people have done so over the years that it doesn't raise any salaries; it's merely that for certain regulatory roles it's good to have someone who knows what it's like to receive the filings so you can make them clear.

It's utterly unlike the legislator->lobbyist revenue model or, say, the Department of the Interior where the regulators were doing drugs and having sex with employees of the companies they were regulating. It's more like "oh, you worked on DevOps at $LARGE_COMPANY_X, our needs are similar to theirs." Not the magic path to riches.


When employees at the FDA leave and take positions at one of the companies they had a hand in approving something for, at an increased salary. The appearance of impropriety is blatant.

Regardless of it actually happening or not it looks terrible. This should never happen


> Regardless of it actually happening or not it looks terrible. This should never happen

I understand the problem you're describing, but consider what you're asking for: people with competence and experience should be barred from taking jobs that require competence and experience? Non-competes have the same problem.


Think of it like a judge. You should be recusing yourself of anything that looks improper.

Public servants have a higher standard they need to adhere to and they simply aren't, it is endemic in the public space.


Public servants are not compensated for that higher standard.


I’m not “compensated” financially when I pick up litter I encounter when walking around but that doesn’t dissuade me from doing so.


When picking up trash substantially impacts your lifetime earnings, that might matter.


I am not in this field, but I guess that as an employee at the FDA you approve drugs for all the big pharma companies, which aside from the FDA are the major employers that value their skillset. It may be that if you prohibit FDA employees to transition to one of the big pharma companies, you're telling them that they can either work at the FDA forever or have to leave their field


Yes, there is a price to pay for being a public servant.


You realize they're not actually servants, right?

"Take a job with the Fed, sign up for a lifetime of lower income so that HN can nod sagely about avoiding the appearance of impropriety" is a recipe to get no one to ever work for the government.


The attitude they aren’t servants to the public is part of the problem


“Hand in approving” is an important factor: approval is such a complex process no one person is really decisive, except possibly at the very very beginning.

Drug companies used to hire multiple trucks simply to deliver their submissions.


> Me and most of America think the FDA approves things according to the highest bidder.

Why do you think this?



Revolving doors between regulators and industry can raise conflict of interest concerns, but this is not at all the same problem that you alluded to above.


Sure it is. Stocks and salaries are definitely financial incentives.


Highest bidder of what?


That really isn’t the truth though. What should be done?


Transparency, in all levels of government.

And quit equating money to speech. Lobbying is legalized bribery and everyone knows it.


[flagged]


That's not true. Trust is a major issue and is directly responsible for anti vaxxer movement. Major corporations and media outlet have made bending the truth (PR spins etc) a legitimate common place practice. Any talking head you see on television /other media is not genuinely trying to convince you. They are all hired hands which will say whatever it takes to produce the results their employers demand. The amount of half truths exaggerations and out right lies we encounter daily is staggering. We thought critical thinking might be the answer, but the overwhelming quantities of adversarial content makes a critical thinker into a conspiracy theorist. If alot of experts lie and tell half truths to benefit themselves why should you believe any expert?


This is nonsense. The anti vaxxers place far more trust on someone who is known to have falsified data, and committed egregious malpractice.

The anti vaxxers lack of trust in the media has almost nothing to do with what the media may or may not have done to lose trust.

The actual difference is that one side does not have a good explanation for what causes autism, and as a result admits that they don’t have the answers yet, while the other does not have a good explanation as well, but makes up stuff and boasts that they actually do know the answer.

For vulnerable parents who are just looking for some answer, the second side is extremely attractive.

Everything else about lack of trust, and corporate influence, etc is all secondary, and are after the fact justifications.


You dont need that falsified data to come to the conclusion vaccinations in the US are a problem. Remove it from the picture.

Compare the US vaccination schedule to any other develop country. Compare our infant mortality rate.

Aside from the differences in the vaccination schedules what is the US doing different from other developed nations. Keeping in mind infants do little but eat food, sleep and see a doctor.

So it's food or healthcare causing the difference. With WIC and the fact poor people qualify for free medical care it's arguable economics dont play much into this.

so explain why the US is so bad at this ?


> Compare our infant mortality rate.

Part of the problem is that the US uses a weird definition for infant mortality that makes it hard to compare across countries.

But even after accounting for that the US is still worse than other countries, and we don't know why.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856058/


The NHS vaccine schedule is just as large as the CDC's: https://assets.publishing.service.gov.uk/government/uploads/...

We're worse at prenatal care. And post-natal care. And there's some serious income inequality problems "poor people qualify for free medical care" doesn't actually obviate things as much as you think it does.


[flagged]


Please don't post flamewar comments to HN.

https://news.ycombinator.com/newsguidelines.html


He has a point. Lately, our federal agencies have really ruined the trust people had in them for so long. Just look at the FAA for instance, not doing their job with Boeing's 737MAX and proving themselves to just be in Boeing's pocket. No one can really trust the FAA any more, and we have to look for European and even Chinese (!) regulators for proper regulation and approving new aircraft before we can trust that they're safe for the flying public to use.

Why is the FDA different? What makes it immune to the sheer corruption that has infected the FAA and other US federal agencies?

And where are foreign drug-regulation agencies anyway? The US isn't the world's gatekeeper to medicine.


Anti-vax stuff aside, the attitude of

>Trust experts or die.

is not a scientific attitude, it is borderline scientism and an appeal to authority. Remember when the tobacco industry paid medical experts such as ENT Doctors to endorse smoking? [0]

The idea that "the rubes" don't have to or shouldn't be allowed to see the data behind FDA decisions and should just trust the experts blindly is completely condescending and is probably a key contributor to anti-vax sentiment and the anti-intellectualism movements you decry.

[0]: https://med.stanford.edu/news/all-news/2012/01/big-tobacco-l...


>is not a scientific attitude

True, but asking non-scientists to have a scientists attitude is ridiculous.

This "everyone is a scientist" idea creates the "everyone is a skeptic" situation, except, when a rube is a skeptic, they're not intellectually skeptical, they're using "skeptic" to mean "bias confirmation".

If you're not a scientist (PhD and publishing) then you don't need a "scientific" attitude.

For the other 99%, you don't need a scientific attitude.

If you are diagnosed with cancer and that diagnosis is confirmed by a second doctor, do you need to demand access to your labs so you can review them personally "with a medical attitude"?

No. Frankly, the only way to have a "scientific attitude" is to spend 4-8 years praciticing in academia. If you don't do that, you can't have the attitude.

You can only pretend. Play makebelieve. Be a pretend scientist. And, almost assuredly, ignore real scientists in the process. After all, due to Illusory Superiority (Dunning-Kruger) you will think yourself just as qualified as the experts. So you will overrule them.

Trust experts or die AKA interdependence in a civilization.


>If you are diagnosed with cancer and that diagnosis is confirmed by a second doctor, do you need to demand access to your labs so you can review them personally "with a medical attitude"?

When considering a medication that is being sold to me such as an anti-depressant with possible long-term harmful side effects, I absolutely want to be familiar with the clinical efficacy and peer reviewed literature on that medication to assess the risks of whether it's worth it for myself.

What about opioids? There were some studies conducted by experts and promoted by the Sacklers that said that opioids were not addictive. Surely I don't have a right to be skeptical of those claims because the surveys were conducted by experts, right? I'm not a post-doc researcher, so obviously I can't tell you that OxyContin is habit-forming.

You're basically arguing for blind trust on the part of the patient, which is very disempowering.

It's very understandable when you present unquestioning obedience and credentialism worship as the only alternative to taking active steps towards being empowered, why people would tell the "experts" to fuck off and trust their own common sense instead as Taleb describes [0]

[0]: https://medium.com/incerto/the-intellectual-yet-idiot-13211e...


Experts are incentivised to be dishonest like everyone else. It's the appeal to authority rather than facts that fuels distrust in agencies.


I'm inclined to agree with you, however the FDA has problems with a lack of transparency. A pharmaceutical company can run 20 studies, and show one result to the FDA that shows safety and efficacy with p < .05. We already have an irreproducibility crisis in science. Medical studies, more than any other type of science, should be pre-registered with the FDA, and the results of those studies should be made public, regardless of their findings.

https://en.wikipedia.org/wiki/Pre-registration_(science)

https://www.xkcd.com/882/


Good way to convince people...

Call them stupid ;)


You were never going to be convinced otherwise by a rational argument. You've literally dismissed the credibility of the American government and the entire field of medicine in a single comment.


Of course I did. After watching the govt and the FDA in action for 5 decades, detassling corn for Monsanto, watching Monsanto sue farmers into submission, seeing increased rates of cancer autism and other issues. Being told everything is ok.

Then I travel the world eating food in other countries and notice the difference in my health. I see the cancer rates in Africa.

You say I am uneducated and stupid. I say I have experience and that experience doesnt jive with your experts statements.

So yeah.... prove you are trustworthy


My argument would be to look into the studies made by numerous universities from all around the world, not just American ones. I have no business telling you whether or not you should trust American government entities, it's not my country. But the world has had medicines and universities for longer than the United States has existed.


You do realize the EU has banned many many things allowed by the FDA because of their studies ?


Isn't that a good thing from your perspective?

My point was that if you don't trust the FDA, there are literally hundreds of other medical and educational institutions you could look to for information.


No one has said everything is ok.

Just by claiming we are being told “everything is ok” you are showing the absolute lies and false straw men and disingenuousness that is at the centre of the anti vax movement.

Somehow you don’t apply even close to the same standards to the anti vax side, where the only evidence is proven to have been falsified.

Also, Anti vaxxers claim they are sick of experts, yet are unwilling to show even the slightest bit of curiosity. Have they seen any iron lungs lately? Maybe they should go talk to their grandparents about the scourge of polio, and how Salk and Sabin were heroes in their time because of their efforts in making the polio vaccine possible.

You don’t even need to go that far in history. Just read current events about measles, and how it’s popping up in precisely the pockets of the US where the anti vaccination movements are strongest, whether it’s religious nutjobs in Texas and Brooklyn, or Hollywood hippie nutjobs in California.


I have more empathy for people who are intellectually stunted and now buy into conspiracy theories. They really never had a choice. If the US or their parents had provided them with sufficient education, maybe it would have been different, but it's hard for me to get as mad at them as you are.

On the other hand, the doctor who knows better, but chooses his own pocket book over the well being of millions is far less empathetic in my mind.

Both people suck in their own way, but I'm less inclined to get worked up about the former.


Why does the truth have to be packaged for believably?

I'm not asking you to change your mind, I'm stating reality.


They are actively resisting scientific data, analysis, and research that overwhelmingly supports vaccines. They may not be stupid, but they are acting like it by putting their beliefs and bias over fact.

I'll stick with actively malicious over stupid as anti-vax is actually crippling and killing people by increasing the spread of diseases that were prevented or eradicated.


How else do we describe the misunderstandings of the uneducated.

Can you blame a high school grad for seeing 1 vaccine death and not understanding those are extremely low probability vs death due to disease?

I think everyone should know Math, but if they cannot, they should defer to professionals.


The stupid can't be convinced anyway. All that remains is to point them out to others.


No, the trust is not gone, and the opinions of an uneducated fringe groups such as the anti-vaxers do not represent the majority in any way. The only reason they get any coverage is because of the perverse click-bait atmosphere of news. Its the tabloidization of news.


[flagged]


"Eschew flamebait. Don't introduce flamewar topics unless you have something genuinely new to say. Avoid unrelated controversies and generic tangents."

https://news.ycombinator.com/newsguidelines.html

Edit: we had to ask you the exact same thing recently. Please don't do this on HN—regardless of how strongly you feel on the topic, it leads to flamewar and the flamewars are all the same.


What you're suggesting already exists. Nobody gets the smallbox vaccine anymore. People only get the rabies vaccine after exposure. There are a handful of vaccines you only need if you're traveling to certain international destinations [1]. The set of vaccines that everyone gets is already subset that everyone needs. And because of people expressing unfounded "skepticism" like this, we're getting outbreaks of diseases that were being kept at bay by the vaccines.

[1] https://www.cdc.gov/features/vaccines-travel/index.html


> I believe that the efficacy of many of them should be put to the test.

https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolesc...

Here's the list. Which ones do you have a problem with?

>I believe that profit-motivated pharmaceutical companies have incentives to make new vaccines -- more sales, and if they're also cheap to make, more profit.this together with some corporate ethics, political regulators, and greedy humans and I think you can see where I'm going with this.

Does this also not apply to Silicon Valley? Insurance? Automobiles? Entertainment? No industry is exempt from human greed and the resulting malfeasance.

> I am just advocating we review how truly necesary they all are. maybe not everybody needs the same set of vaccines? (thou I don't doubt there's a subset everyone needs)

Well, no vaccine is truly necessary. Its preventative, to reduce harm from potential exposure to disease causing antigens. You could go through life without encountering any of those pathogens. Also, its not like a random idiot bureaucrat that lists a vaccine as "needed" because his palms got greased. This is a public committee whose meetings and work you can easily follow https://en.wikipedia.org/wiki/Advisory_Committee_on_Immuniza...

>second note: unwritten rule of HN, do not question vaccines.

Can you provide a rationale for your questioning?


The efficacy of vaccines is tested as part of the approval process, vaccines are not profit centres for anyone, I award you zero points and may God have mercy on your soul.


> I am just advocating we review how truly necesary they all are. maybe not everybody needs the same set of vaccines?

Is this something you believe no one has done so far?


You are not being downvoted for questioning vaccines generally. You are being downvoted for specifically suggesting something that has already been done and is continuing to be done already.


third note: don't whine about being downvoted.


Last Week Tonight with John Oliver did a segment on this recently: https://youtu.be/-tIdzNlExrw




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