6 ms·

> For a drug to be approved by the Food and Drug Administration, it must prove itself better than a placebo, or fake drug. False, the FDA doesn't actually have

> For a drug to be approved by the Food and Drug Administration, it must prove itself better than a placebo, or fake drug. False, the FDA doesn't actually have any requirement to prove that a treatment is better than placebo. Many trials don't even include a placebo arm, they only compare themselves against existing drugs that were grandfathered into the system without any efficacy testing. Or they compare themselves to inert placebos rather than active ones, even if they are psychoactive drugs. Or they only compare themselves against placebos for a few weeks, even if they are meant to be used for long periods of time. This is how we have drugs like antidepressants and ADHD drugs on the market even the though research shows they are actually worse than taking no drug at all.

viewer5 12y ago
> antidepressants and ADHD drugs on the market even the though research shows they are actually worse than taking no drug at all What do you mean?
- Alex3917 12y ago
  http://www.amazon.com/gp/product/0307452425/ref=s9_simh_gw_p14_d0_i1?pf_rd_m=ATVPDKIKX0DER&pf_rd_s=center-2&pf_rd_r=1T1TZZVVDR83AX2SD7HT&pf_rd_t=101&pf_rd_p=1688200382&pf_rd_i=507846 http://www.amazon.com/gp/product/0307452425/ref=s9_simh_gw_p... http://www.amazon.com/gp/product/0465022006/ref=s9_simh_gw_p14_d0_i2?pf_rd_m=ATVPDKIKX0DER&pf_rd_s=center-2&pf_rd_r=1T1TZZVVDR83AX2SD7HT&pf_rd_t=101&pf_rd_p=1688200382&pf_rd_i=507846 http://www.amazon.com/gp/product/0465022006/ref=s9_simh_gw_p...
  - refurb 12y ago
    Rather than linking to a book on Amazon, could you link to some peer-reviewed journal articles?
    - Alex3917 12y ago
      Both of these books are just writeups on peer reviewed journal articles. No individual article is going to tell you very much on its own, so I don't see much value in just linking to a random list of studies.
      - mbreese 12y ago
        A review article (academic) then...
    - pessimizer 12y ago
      http://alphachoices.com/repository/assets/pdf/EmperorsNewDrugs.pdf http://alphachoices.com/repository/assets/pdf/EmperorsNewDru... http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0050045 http://www.plosmedicine.org/article/info:doi/10.1371/journal...
      - refurb 12y ago
        The PLOS article isn't really news. It's been known for a long time that measuring the efficacy of drugs for CNS diseases is ridiculously hard.
        pessimizer 12y ago
        The article doesn't say that it's hard, it says that when you do it, there aren't significant benefits over placebo.
        refurb 12y ago
        The article doesn't say that, what it says is"Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. ". The other thing to keep in mind is that this was a meta-analysis using data pooled across many different trials. It certainly isn't as rigorous as a RCT.[1] [1]http://www.ccjm.org/content/75/6/431.full http://www.ccjm.org/content/75/6/431.full
        Alex3917 12y ago
        > "Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective." You seem to be taking that demonstrate efficacy, when what they're actually saying is more like 'there is no evidence that this works, but if nothing works then why the hell not.' It's no different than doctors giving patients the go ahead to use alternative medicine or whatever when the doctors know the patient is already going to die from cancer regardless.
lisper 12y ago
> inert placebos rather than active ones Isn't "active placebo" a contradiction in terms?
- beagle3 12y ago
  No. Because people know they could be taking a placebo, then having undeniable effect (psychoactive, redness, soreness, etc.) tells them that they are not using the placebo. Conversely, having no undeniable side effects lets them know that they are using the placebo. Thus, placebo usage is undermined. "Active placebo" has an undeniable effect, but not the compound being tested, so that the test subjects cannot tell if they have the placebo or the real things.
  - nitid_name 12y ago
    Couldn't that raise the question of if the side effects themselves are a source of benefit?
    - acornax 12y ago
      Not if they're already understood not to be...
    - Alex3917 12y ago
      This is what the book The Emperor's New Drugs is about. The idea of the book is that there was some well-known research showing that anti-depressants are effective for severe depression, but not mild or moderate cases. But if you actually only look at studies that used active placebos as controls, then there is no evidence clinical efficacy even for severe depression. Meaning that the nominal benefit for anti-depressants for severe depression that's seen in many studies is in fact probably due to people thinking they are better due to the side effects of the drug, rather than due to true drug benefits.
      - mjevans 12y ago
        It could also be that participating in the study addresses sources of depression by giving the subject a way that they are 'helping out' society, or are 'cared about' etc. There are probably many factors to depression which may include chemical or structural causes; however the human brain is a complex self adapting analog computer. It would be foolish to think that such a system can be reduced a single or even simple set of controlled variables.
harvestmoon 12y ago
While there is a good amount of controversy around the efficacy of antidepressants, first-line ADHD medications (the stimulants) work in roughly 70% of cases, which is much superior to placebo. For those with ADHD, treatment can make a large quality of life improvement. Source - memory from having written a book on adult ADHD
- Alex3917 12y ago
  > first-line ADHD medications (the stimulants) work in roughly 70% of cases What do you mean by 'work'? The research cited by Anatomy of an Epidemic shows that there is no affect on grades or other academic outcomes. And that while concentration itself improves somewhat in the short term, after 2+ years it is worse than if the person were never given the drugs to begin with. See also: http://online.wsj.com/news/articles/SB10001424127887323368704578593660384362292 http://online.wsj.com/news/articles/SB1000142412788732336870...
  - wiredfool 12y ago
    Academic performance doesn't seem to be an optimal measure for Adult ADHD.
    - pessimizer 12y ago
      What is? Self-reporting?
  - jeangenie 12y ago
    The history behind ADD medications (http://en.wikipedia.org/wiki/Obetrol http://en.wikipedia.org/wiki/Obetrol) is also troubling. This is a drug designed to induce weight loss in adults and today it's widely given to children and even toddlers (http://www.today.com/health/thats-nuts-10-000-toddlers-get-drugs-adhd-2D79684452 http://www.today.com/health/thats-nuts-10-000-toddlers-get-d...).
  - Houshalter 12y ago
    That's deeply concerning. Everything I've read highly recommended medication. People with ADHD report it significantly improved their lives. Can anyone say if this article is reliable? I can't even read it on this computer.
taeric 12y ago
I'm not sure I understand the first scenario. If they are tested against drugs which have already been shown to be better than a placebo, doesn't basic logic show they would be, as well? Or is there a case where one could "pass" this test, but still "lose" against a placebo? For the rest, I didn't realize there was a difference between inert and active placebos.
- Alex3917 12y ago
  > Or is there a case where one could "pass" this test, but still "lose" against a placebo? The main issue is that a lot of the existing drugs aren't better than placebos: - Some were never required to be tested for efficacy by the FDA before approval. - Some were tested for whatever reason., but the methodology used by testing was flawed for whatever reason. - In many the data was blatantly faked or manipulated by the company running the test. In general NIH tests show much lower efficacy for the same drugs as in pharma trials sponsored by the drug manufacturer. There is tons of research on this. However, there are other tricks that pharma companies use when testing against existing drugs. One of the main ones is using non-effective doses of the older drugs... E.g. by using a higher than normal dose of the older drug in order to make it look like the newer drug has less side effects. This is how the newer generation of anti-psychotics got approved, and it's also how Nexium got approved even though it's basically chemically identical to Prilosec.
  - refurb 12y ago
    Some were never required to be tested for efficacy by the FDA before approval Yes they were used before the FDA had a formal approval process, but your comments doesn't make sense. If the current standard of care is a drug and you test against it, aren't you showing it's more effective?
    - Alex3917 12y ago
      > If the current standard of care is a drug and you test against it, aren't you showing it's more effective? The main issue is that a drug can be more effective than an older drug but still be less effective than taking no drug at all. But given all the problems, both theoretical and practical, with current drug trials, there is pretty much no guarantee of anything. Just because something makes sense on paper doesn't mean that it's actually true. There are a number of books about the issues with drug trials... Bad Pharma by Ben Goldacre, The Truth About Drug Companies by Marcia Angell, Overdosed America, etc. All of these books cover largely different issues, so imho it's worth reading them all.

viewer5 12y ago

> antidepressants and ADHD drugs on the market even the though research shows they are actually worse than taking no drug at all What do you mean?

Alex3917 12y ago
http://www.amazon.com/gp/product/0307452425/ref=s9_simh_gw_p14_d0_i1?pf_rd_m=ATVPDKIKX0DER&pf_rd_s=center-2&pf_rd_r=1T1TZZVVDR83AX2SD7HT&pf_rd_t=101&pf_rd_p=1688200382&pf_rd_i=507846 http://www.amazon.com/gp/product/0307452425/ref=s9_simh_gw_p... http://www.amazon.com/gp/product/0465022006/ref=s9_simh_gw_p14_d0_i2?pf_rd_m=ATVPDKIKX0DER&pf_rd_s=center-2&pf_rd_r=1T1TZZVVDR83AX2SD7HT&pf_rd_t=101&pf_rd_p=1688200382&pf_rd_i=507846 http://www.amazon.com/gp/product/0465022006/ref=s9_simh_gw_p...
- refurb 12y ago
  Rather than linking to a book on Amazon, could you link to some peer-reviewed journal articles?
  - Alex3917 12y ago
    Both of these books are just writeups on peer reviewed journal articles. No individual article is going to tell you very much on its own, so I don't see much value in just linking to a random list of studies.
    - mbreese 12y ago
      A review article (academic) then...
  - pessimizer 12y ago
    http://alphachoices.com/repository/assets/pdf/EmperorsNewDrugs.pdf http://alphachoices.com/repository/assets/pdf/EmperorsNewDru... http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0050045 http://www.plosmedicine.org/article/info:doi/10.1371/journal...
    - refurb 12y ago
      The PLOS article isn't really news. It's been known for a long time that measuring the efficacy of drugs for CNS diseases is ridiculously hard.
      - pessimizer 12y ago
        The article doesn't say that it's hard, it says that when you do it, there aren't significant benefits over placebo.
        refurb 12y ago
        The article doesn't say that, what it says is"Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. ". The other thing to keep in mind is that this was a meta-analysis using data pooled across many different trials. It certainly isn't as rigorous as a RCT.[1] [1]http://www.ccjm.org/content/75/6/431.full http://www.ccjm.org/content/75/6/431.full
        Alex3917 12y ago
        > "Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective." You seem to be taking that demonstrate efficacy, when what they're actually saying is more like 'there is no evidence that this works, but if nothing works then why the hell not.' It's no different than doctors giving patients the go ahead to use alternative medicine or whatever when the doctors know the patient is already going to die from cancer regardless.

lisper 12y ago

> inert placebos rather than active ones Isn't "active placebo" a contradiction in terms?

beagle3 12y ago
No. Because people know they could be taking a placebo, then having undeniable effect (psychoactive, redness, soreness, etc.) tells them that they are not using the placebo. Conversely, having no undeniable side effects lets them know that they are using the placebo. Thus, placebo usage is undermined. "Active placebo" has an undeniable effect, but not the compound being tested, so that the test subjects cannot tell if they have the placebo or the real things.
- nitid_name 12y ago
  Couldn't that raise the question of if the side effects themselves are a source of benefit?
  - acornax 12y ago
    Not if they're already understood not to be...
  - Alex3917 12y ago
    This is what the book The Emperor's New Drugs is about. The idea of the book is that there was some well-known research showing that anti-depressants are effective for severe depression, but not mild or moderate cases. But if you actually only look at studies that used active placebos as controls, then there is no evidence clinical efficacy even for severe depression. Meaning that the nominal benefit for anti-depressants for severe depression that's seen in many studies is in fact probably due to people thinking they are better due to the side effects of the drug, rather than due to true drug benefits.
    - mjevans 12y ago
      It could also be that participating in the study addresses sources of depression by giving the subject a way that they are 'helping out' society, or are 'cared about' etc. There are probably many factors to depression which may include chemical or structural causes; however the human brain is a complex self adapting analog computer. It would be foolish to think that such a system can be reduced a single or even simple set of controlled variables.

harvestmoon 12y ago

While there is a good amount of controversy around the efficacy of antidepressants, first-line ADHD medications (the stimulants) work in roughly 70% of cases, which is much superior to placebo. For those with ADHD, treatment can make a large quality of life improvement. Source - memory from having written a book on adult ADHD

Alex3917 12y ago
> first-line ADHD medications (the stimulants) work in roughly 70% of cases What do you mean by 'work'? The research cited by Anatomy of an Epidemic shows that there is no affect on grades or other academic outcomes. And that while concentration itself improves somewhat in the short term, after 2+ years it is worse than if the person were never given the drugs to begin with. See also: http://online.wsj.com/news/articles/SB10001424127887323368704578593660384362292 http://online.wsj.com/news/articles/SB1000142412788732336870...
- wiredfool 12y ago
  Academic performance doesn't seem to be an optimal measure for Adult ADHD.
  - pessimizer 12y ago
    What is? Self-reporting?
- jeangenie 12y ago
  The history behind ADD medications (http://en.wikipedia.org/wiki/Obetrol http://en.wikipedia.org/wiki/Obetrol) is also troubling. This is a drug designed to induce weight loss in adults and today it's widely given to children and even toddlers (http://www.today.com/health/thats-nuts-10-000-toddlers-get-drugs-adhd-2D79684452 http://www.today.com/health/thats-nuts-10-000-toddlers-get-d...).
- Houshalter 12y ago
  That's deeply concerning. Everything I've read highly recommended medication. People with ADHD report it significantly improved their lives. Can anyone say if this article is reliable? I can't even read it on this computer.

taeric 12y ago

I'm not sure I understand the first scenario. If they are tested against drugs which have already been shown to be better than a placebo, doesn't basic logic show they would be, as well? Or is there a case where one could "pass" this test, but still "lose" against a placebo? For the rest, I didn't realize there was a difference between inert and active placebos.

Alex3917 12y ago
> Or is there a case where one could "pass" this test, but still "lose" against a placebo? The main issue is that a lot of the existing drugs aren't better than placebos: - Some were never required to be tested for efficacy by the FDA before approval. - Some were tested for whatever reason., but the methodology used by testing was flawed for whatever reason. - In many the data was blatantly faked or manipulated by the company running the test. In general NIH tests show much lower efficacy for the same drugs as in pharma trials sponsored by the drug manufacturer. There is tons of research on this. However, there are other tricks that pharma companies use when testing against existing drugs. One of the main ones is using non-effective doses of the older drugs... E.g. by using a higher than normal dose of the older drug in order to make it look like the newer drug has less side effects. This is how the newer generation of anti-psychotics got approved, and it's also how Nexium got approved even though it's basically chemically identical to Prilosec.
- refurb 12y ago
  Some were never required to be tested for efficacy by the FDA before approval Yes they were used before the FDA had a formal approval process, but your comments doesn't make sense. If the current standard of care is a drug and you test against it, aren't you showing it's more effective?
  - Alex3917 12y ago
    > If the current standard of care is a drug and you test against it, aren't you showing it's more effective? The main issue is that a drug can be more effective than an older drug but still be less effective than taking no drug at all. But given all the problems, both theoretical and practical, with current drug trials, there is pretty much no guarantee of anything. Just because something makes sense on paper doesn't mean that it's actually true. There are a number of books about the issues with drug trials... Bad Pharma by Ben Goldacre, The Truth About Drug Companies by Marcia Angell, Overdosed America, etc. All of these books cover largely different issues, so imho it's worth reading them all.