7 ms·

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

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.

gumby 7y ago
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.
- bilbo0s 7y ago
  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.
  - abrichr 7y ago
    Sounds interesting! Which startup?
criley2 7y ago
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-access 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.
- briffle 7y ago
  > 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..
  - criley2 7y ago
    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_settlements 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.
ghaff 7y ago
>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.)
whiddershins 7y ago
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.
skybrian 7y ago
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?
- chimeracoder 7y ago
  > 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.
  - skybrian 7y ago
    As long as they're not worse, it could result in more approved drugs.
  - Symmetry 7y ago
    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.
    - chimeracoder 7y ago
      > 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.
      - Symmetry 7y ago
        No, but it is a reason you might want to be able to buy drugs imported from Europe.
Macross8299 7y ago
>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 https://www.nytimes.com/2008/01/17/health/17depress.html [1]: http://www.washingtonpost.com/wp-dyn/articles/A9802-2004Sep9.html http://www.washingtonpost.com/wp-dyn/articles/A9802-2004Sep9...
- rscho 7y ago
  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.
  - bilbo0s 7y ago
    >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.
smackay 7y ago
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_Administration https://en.wikipedia.org/wiki/History_of_the_Food_and_Drug_A...
adam 7y ago
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.
- throwayEngineer 7y ago
  >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.
  - dractori 7y ago
    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.
    - throwayEngineer 7y ago
      In every country, in every world, in every decade of humanity, in every department. But this time will be different. Very interesting take.
- hurrdurr2 7y ago
  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.
lekanwang 7y ago
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.
WalterBright 7y ago
> 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.
- hennas962500 7y ago
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gumby 7y ago

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.

bilbo0s 7y ago
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.
- abrichr 7y ago
  Sounds interesting! Which startup?

criley2 7y ago

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-access 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.

briffle 7y ago
> 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..
- criley2 7y ago
  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_settlements 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.

ghaff 7y ago

>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.)

whiddershins 7y ago

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.

skybrian 7y ago

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?

chimeracoder 7y ago
> 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.
- skybrian 7y ago
  As long as they're not worse, it could result in more approved drugs.
- Symmetry 7y ago
  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.
  - chimeracoder 7y ago
    > 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.
    - Symmetry 7y ago
      No, but it is a reason you might want to be able to buy drugs imported from Europe.

Macross8299 7y ago

>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 https://www.nytimes.com/2008/01/17/health/17depress.html [1]: http://www.washingtonpost.com/wp-dyn/articles/A9802-2004Sep9.html http://www.washingtonpost.com/wp-dyn/articles/A9802-2004Sep9...

rscho 7y ago
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.
- bilbo0s 7y ago
  >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.

smackay 7y ago

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

adam 7y ago

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.

throwayEngineer 7y ago
>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.
- dractori 7y ago
  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.
  - throwayEngineer 7y ago
    In every country, in every world, in every decade of humanity, in every department. But this time will be different. Very interesting take.
hurrdurr2 7y ago
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.

lekanwang 7y ago

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.

WalterBright 7y ago

> 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.

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