6 ms·

> More radically, it might be possible to repeal the 1962 Kefauver-Harris amendment to the Federal Food, Drug, and Cosmetic Act, a provision that requires drug

> More radically, it might be possible to repeal the 1962 Kefauver-Harris amendment to the Federal Food, Drug, and Cosmetic Act, a provision that requires drug developers to prove a medication's efficacy (rather than just its safety) before it can receive FDA approval. Since this more stringent authorization process was enacted, the average number of new drugs greenlighted per year has dropped by more than half, while the death rate from drug toxicity stayed constant. The additional regulation has produced stagnation, in other words, with no upside in terms of improved safety. If that were to happen, we can expect that the drug market would become like the supplement market: full of pseudo-science and products that do nothing. Right now, supplement makers are prohibited from making specific medical claims; they can say something like "gives you energy," but they can't say "cures cancer." The only reason they don't is because they legally can't. (And even then they sometimes do, and sometimes get away with it.) If they were suddenly allowed to, we would not get a flood of new drugs from the current pharmaceutical companies. We would get a flood of sugar pills from the current supplement companies. The "since" part of the paragraph is also a bit of non-sequitur. Before and after the 1962 provision, drug companies had to prove safety, so it's not a surprise the death rate from drug toxicity stayed constant. Proving efficacy is about preventing companies from exploiting the public by selling stuff that has no hope of ever working as advertised. The blind spot of proposals like this is that they assume good-faith actors acting rationally. They completely ignore bad-faith actors willing to sociopathically exploit people.

bryanrasmussen 8y ago
are you sure it's really a blind spot and not a bad faith proposal itself?
raverbashing 8y ago
I think there are deeper questions to be asked: - What is the false negative rate for currently mandated FDA mandated efficacy studies? - How can studies be improved so it identifies good/bad drug candidates better and quicker?
- nonbel 8y ago
  >"How can studies be improved so it identifies good/bad drug candidates better and quicker?" These are not at all hard to identify, but too many people have "bought in" to the bad methods and incorrect results they generated. The main obstacle to progress in medical research is political rather than scientific. Are you willing to give up cherished beliefs like "tobacco smoke is a strong carcinogen", or "amyloid-beta causes alzheimers", to get cures for diseases?
CryptoPunk 8y ago
>>If they were suddenly allowed to, we would not get a flood of new drugs from the current pharmaceutical companies. We would get a flood of sugar pills from the current supplement companies. We would get a flood of data from human use of the drug, increasing the rate at which efficacy is discovered in drugs. There may be paths to exploitation mitigation that do far less harm to the rate of good-faith experimentation.
- scott_s 8y ago
  I don't see how one follows from the other. If what you said is true, we would expect the rate at which efficacy in supplements to have already increased, but it has not. The effect that I think the original article is missing is that sometimes when you radically change the rules in an industry, different actors take over the industry. If drugs don't have to prove efficacy, companies willing to sell drugs with no hope of ever being effective will massively outcompete those that even try a little - it's just massively easier and more profitable.
  - CryptoPunk 8y ago
    It follows that more human data increases the rate of discovery, ceteris paribus. The medical profession would need to hold itself, or be held, to a higher standard than supplement marketers are, for the negative outcomes you describe to not materialize. We can't have a repeat of the surge in opioid prescriptions since the 1990s, where doctors have been compensated by pharmaceuticals for prescribing opioids. Something a long the lines of Bartley Madden's proposal of requiring doctors to document the results of the use of this class of drugs (those proven safe but not proven effective) in an open access database could go a long way in producing useful information.
    - scott_s 8y ago
      More data is not the same as more good data. And there certainly is such a thing as bad data. And I don't trust all doctors enough to rely on them to sift through the real versus the fake. Doctors are not scientists. Further, since drug makers can market directly to consumers, they will start asking for the fake stuff because the fake stuff will make fantastical claims. You're also side-stepping the issue of over-the-counter drugs. With no efficacy required, we will see a proliferation of sugar pills making specific claims about pain, inflammation, fever suppression, decongestion and allergy reduction that don't require a prescription.
drewg123 8y ago
How does this act relate to drugs targeted to specific genetic markers? I think we're moving into an era when we need to consider that everybody is different, and a lot of cancers are different. This isn't like curing a bacteria, where (mostly) one-size fits all. I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker, but is safe and will cure cancer for those with the marker?
- jcranmer 8y ago
  I believe so, but you do have to make sure your drug application clearly labels when it is safe to use.
- chimeracoder 8y ago
  > I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker We already do this. A large class of both antipsychotics and antidepressants require certain genes in order to metabolize properly and have the intended effect, instead of just giving a bunch of side effects with no benefit. These genes are not universal and not evenly distributed; people of certain ethnic backgrounds are dramatically less likely to have the requisite genes, which means that most antipsychotics and antidepressants literally don't work on them.
  - perl4ever 8y ago
    Do you have a citation for this?
- mjewkes 8y ago
  Yes - if you prove that it is safer than other options for the indicated population, the FDA will approve it with a label indicating it only for that population. Indications can be as specific as "indicated for tumors with specific mutations"[1] or indicated "prostate cancer when all other options have failed"[2] [1]https://en.wikipedia.org/wiki/Pembrolizumab https://en.wikipedia.org/wiki/Pembrolizumab [2]https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm613543.htm https://www.fda.gov/drugs/informationondrugs/approveddrugs/u...
ikeboy 8y ago
Off-label uses of drugs don't need to show efficacy but don't suffer from that problem. Doctors prescribe off-label based on what consensus has shown works even without FDA approved studies.
r_smart 8y ago
As a libertarian, Reason annoys the bejesus out of me. As a human, journalists annoy the bejesus out of me. The real test here is, are drugs more efficacious then prior to the legislation. If not, we need to review it. I'd argue repeal, others would argue replace. I'd look forward to vigorous debate, but first we have to do some actual work to figure out if this legislation is effective. If it is leave it alone. There's probably lots of other stuff we can look at to review, much of which is nothing but drag on the system. Journalists, of course, have no interest in the truth or doing work that doesn't involve twitter.
gowld 8y ago
You are missing the key point. Supplements are allowed because they are made of "Generally Recognized As Safe (GRAS)" ingredients. New drugs aren't, and that's the point. Experimental drugs are obviously risky.
valuearb 8y ago
When did I give the FDA authority over what i put in my body?
alan-crowe 8y ago
The big hope for people who suffer from ME/CFS is an off-label use of an existing drug such as Rituximab. Under the current system, drugs go through phase I trials to make sure that they are safe enough for doctors to prescribe. Then they go through phase II trials to get a feel for dosage and effect size for the intended indication. Then they fail at phase III because they compare poorly with an existing drug for that indication. What determines whether ME/CFS patients get to try a drug, to see if it does anything for them? Phase I and II results. Fair enough. But also Phase III. So the efficacy of the drug for a different indication plays a positive roll. If Rituximab were ineffective for leukemia, it would be forbidden to explore it for ME/CFS in a way that might later justify a big trial to check for efficacy. Given the side-effects of Rituximab, that is fair enough, but the law is equally restrictive on all that failed in Phase III. So drugs with mild side-effects that did nothing for the intended indication cannot be explored for ME/CFS. That is sad. Those who believe that ME/CFS is due to a viral infection would love to try a failed anti-viral. Those who believe that ME/CFS is an auto-immune disease would love to try a failed treatment for Irritable Bowel Syndrome. Meanwhile, researchers tend to stay away from diseases with such unclear etiology. But the efficacy requirement has worse implications. As wikipedia puts it > Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. So a drug that passes Phase I and Phase II can be eligible or ineligible for off label exploration because of the efficacy of a different drug for a different indication.

bryanrasmussen 8y ago

are you sure it's really a blind spot and not a bad faith proposal itself?

raverbashing 8y ago

I think there are deeper questions to be asked: - What is the false negative rate for currently mandated FDA mandated efficacy studies? - How can studies be improved so it identifies good/bad drug candidates better and quicker?

nonbel 8y ago
>"How can studies be improved so it identifies good/bad drug candidates better and quicker?" These are not at all hard to identify, but too many people have "bought in" to the bad methods and incorrect results they generated. The main obstacle to progress in medical research is political rather than scientific. Are you willing to give up cherished beliefs like "tobacco smoke is a strong carcinogen", or "amyloid-beta causes alzheimers", to get cures for diseases?

CryptoPunk 8y ago

>>If they were suddenly allowed to, we would not get a flood of new drugs from the current pharmaceutical companies. We would get a flood of sugar pills from the current supplement companies. We would get a flood of data from human use of the drug, increasing the rate at which efficacy is discovered in drugs. There may be paths to exploitation mitigation that do far less harm to the rate of good-faith experimentation.

scott_s 8y ago
I don't see how one follows from the other. If what you said is true, we would expect the rate at which efficacy in supplements to have already increased, but it has not. The effect that I think the original article is missing is that sometimes when you radically change the rules in an industry, different actors take over the industry. If drugs don't have to prove efficacy, companies willing to sell drugs with no hope of ever being effective will massively outcompete those that even try a little - it's just massively easier and more profitable.
- CryptoPunk 8y ago
  It follows that more human data increases the rate of discovery, ceteris paribus. The medical profession would need to hold itself, or be held, to a higher standard than supplement marketers are, for the negative outcomes you describe to not materialize. We can't have a repeat of the surge in opioid prescriptions since the 1990s, where doctors have been compensated by pharmaceuticals for prescribing opioids. Something a long the lines of Bartley Madden's proposal of requiring doctors to document the results of the use of this class of drugs (those proven safe but not proven effective) in an open access database could go a long way in producing useful information.
  - scott_s 8y ago
    More data is not the same as more good data. And there certainly is such a thing as bad data. And I don't trust all doctors enough to rely on them to sift through the real versus the fake. Doctors are not scientists. Further, since drug makers can market directly to consumers, they will start asking for the fake stuff because the fake stuff will make fantastical claims. You're also side-stepping the issue of over-the-counter drugs. With no efficacy required, we will see a proliferation of sugar pills making specific claims about pain, inflammation, fever suppression, decongestion and allergy reduction that don't require a prescription.

drewg123 8y ago

How does this act relate to drugs targeted to specific genetic markers? I think we're moving into an era when we need to consider that everybody is different, and a lot of cancers are different. This isn't like curing a bacteria, where (mostly) one-size fits all. I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker, but is safe and will cure cancer for those with the marker?

jcranmer 8y ago
I believe so, but you do have to make sure your drug application clearly labels when it is safe to use.
chimeracoder 8y ago
> I wonder: is it possible to bring a drug to market that is ineffective and sometimes fatal to most people without a genetic marker We already do this. A large class of both antipsychotics and antidepressants require certain genes in order to metabolize properly and have the intended effect, instead of just giving a bunch of side effects with no benefit. These genes are not universal and not evenly distributed; people of certain ethnic backgrounds are dramatically less likely to have the requisite genes, which means that most antipsychotics and antidepressants literally don't work on them.
- perl4ever 8y ago
  Do you have a citation for this?
mjewkes 8y ago
Yes - if you prove that it is safer than other options for the indicated population, the FDA will approve it with a label indicating it only for that population. Indications can be as specific as "indicated for tumors with specific mutations"[1] or indicated "prostate cancer when all other options have failed"[2] [1]https://en.wikipedia.org/wiki/Pembrolizumab https://en.wikipedia.org/wiki/Pembrolizumab [2]https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm613543.htm https://www.fda.gov/drugs/informationondrugs/approveddrugs/u...

ikeboy 8y ago

Off-label uses of drugs don't need to show efficacy but don't suffer from that problem. Doctors prescribe off-label based on what consensus has shown works even without FDA approved studies.

r_smart 8y ago

As a libertarian, Reason annoys the bejesus out of me. As a human, journalists annoy the bejesus out of me. The real test here is, are drugs more efficacious then prior to the legislation. If not, we need to review it. I'd argue repeal, others would argue replace. I'd look forward to vigorous debate, but first we have to do some actual work to figure out if this legislation is effective. If it is leave it alone. There's probably lots of other stuff we can look at to review, much of which is nothing but drag on the system. Journalists, of course, have no interest in the truth or doing work that doesn't involve twitter.

gowld 8y ago

You are missing the key point. Supplements are allowed because they are made of "Generally Recognized As Safe (GRAS)" ingredients. New drugs aren't, and that's the point. Experimental drugs are obviously risky.

valuearb 8y ago

When did I give the FDA authority over what i put in my body?

alan-crowe 8y ago

The big hope for people who suffer from ME/CFS is an off-label use of an existing drug such as Rituximab. Under the current system, drugs go through phase I trials to make sure that they are safe enough for doctors to prescribe. Then they go through phase II trials to get a feel for dosage and effect size for the intended indication. Then they fail at phase III because they compare poorly with an existing drug for that indication. What determines whether ME/CFS patients get to try a drug, to see if it does anything for them? Phase I and II results. Fair enough. But also Phase III. So the efficacy of the drug for a different indication plays a positive roll. If Rituximab were ineffective for leukemia, it would be forbidden to explore it for ME/CFS in a way that might later justify a big trial to check for efficacy. Given the side-effects of Rituximab, that is fair enough, but the law is equally restrictive on all that failed in Phase III. So drugs with mild side-effects that did nothing for the intended indication cannot be explored for ME/CFS. That is sad. Those who believe that ME/CFS is due to a viral infection would love to try a failed anti-viral. Those who believe that ME/CFS is an auto-immune disease would love to try a failed treatment for Irritable Bowel Syndrome. Meanwhile, researchers tend to stay away from diseases with such unclear etiology. But the efficacy requirement has worse implications. As wikipedia puts it > Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. So a drug that passes Phase I and Phase II can be eligible or ineligible for off label exploration because of the efficacy of a different drug for a different indication.