13 ms·

Are Placebos Really Sugar Pills?

471 points by techdog 14y ago

acchow 14y ago
As an aside, sugars aren't biologically inert either.
- Florin_Andrei 14y ago
  So, is there anything that could be said to be biologically inert in any and every scenario?
  - cotsuka 14y ago
    Chalk?
    - josscrowcroft 14y ago
      Calcium, surely..
      - masklinn 14y ago
        Calcium can interact with a number of other chemicals, potentially negatively (for the surrounding organism). Although doses are probably important in judging that. http://en.wikipedia.org/wiki/Calcium_metabolism#Interaction_with_other_chemicals http://en.wikipedia.org/wiki/Calcium_metabolism#Interaction_...
    - masklinn 14y ago
      Cellulose as well? Dicalcium phosphate is also a common tablet filler, though I don't know if it's biologically inactive.
    - ahi 14y ago
      It has antacid properties.
  - ahi 14y ago
    Probably not, but disclosure of placebo ingredients would be enough to determine if it was a wise choice for a particular study.
  - user24 14y ago
    Gold?
    - Locke1689 14y ago
      Gold allergy.
  - trotsky 14y ago
    A quote from the press release about the paper the OP cites: But, according to the paper's author, Beatrice Golomb, MD, PhD, associate professor of medicine at the University of California, San Diego School of Medicine, this standard has a fundamental problem, "there isn't anything actually known to be physiologically inert." http://www.sciencedaily.com/releases/2010/10/101018174335.htm http://www.sciencedaily.com/releases/2010/10/101018174335.ht...
  - marvin 14y ago
    Cellulose? Diamond? Glass? Ceramics?
    - acchow 14y ago
      I believe glass should work. Maybe teflon?
- sek 14y ago
  Everybody consumes a huge amount of sugar every day, so the pill is not even measurable compared to your normal intake. So on average the effect of this small amount of sugar disappears.
- driverdan 14y ago
  Unless you're studying something related to blood sugar, insulin, etc or the user has a condition impacted by sugar, such as diabetes, a small amount of sugar (pills would contain 100-1000mg) isn't going to have any impact.
cooldeal 14y ago
Aren't the side effects mimicked so that participants won't see the lack of them and then know that they're taking the placebo which will defeat the double blind study? For example, if you're testing fish oil, you wouldn't use a sugar pill since it's easy to know what you're taking by looking at it. You would use something like olive oil.
- newishuser 14y ago
  There are certainly ways to simulate fish oil with biologically inert ingredients.
  - pmelendez 14y ago
    I think you're missing the point. He was talking about this section of the article: >That way, of course, they can say things in their ads like "[drug name] has a low occurrence of side effects, such as dry mouth, which occurred about as often as they did with placebo." cooldeal point is that you need to mimic the side effects to make the control group believable. Whether it is needed to use inert components or not would depend on the nature of the drug in test.
  - kragen 14y ago
    There are? What do you have in mind? If you use mineral oil or Olean, you get diarrhea as a side effect in doses of more than a few grams per day.
- pygy_ 14y ago
  Indeed. It is well known that SSRIs studies were biased because of this, because SSRIs have a lot of early side effects, which break the blinding. Knowing that you're in the treatment branch increases the placebo effect. That being said, the opacity of the manufacture process is concerning. Studies with active placebos should have a third branch with inert placebos, to assess the incidence of side effects.
  - Locke1689 14y ago
    That presents massive ethical issues. One would have to knowingly not give subjects a drug that we know helps them (i.e., the current standard of care).
newishuser 14y ago
What this article leads me to think is that we need to legally protect the word placebo. It seems grossly misleading to use the word placebo to describe non biologically inert ingredients. To do so is to lie and nothing more.
- wiredfool 14y ago
  Just look for homeopathic remedies then. Guaranteed not to have any active ingredients.
  - joshuacc 14y ago
    That's not strictly true. Homeopathic remedies do often include small amounts of alcohol or sugar.
    - hellerbarde 14y ago
      unless it's homeopathic alcohol :P http://homeopathicvodka.com/ http://homeopathicvodka.com/
  - plorkyeran 14y ago
    Not everything that claims to be homeopathic actually is. One example is Traumeel. If you look at their ingredients ( http://www.traumeel.us/Products/ProductDetail.aspx?id=1901000 http://www.traumeel.us/Products/ProductDetail.aspx?id=190100... ), there's enough active ingredients that are only 1X diluted that the total is over .5% active. I assume it's just labeled as homeopathic because they failed to fake some clinical trials to get FDA approval (or didn't even try), but maybe it's actually an effective marketing choice.
- jessriedel 14y ago
  Actually, I think "Placebo" has always meant "a thing used to make not taking a drug an indistinguishable experience to taking it" (which, it turns out upon reflection, requires it to inflict side effects). Inertness is just a popular misconception. That said, I think capitalizing on that misconception is wrong and that it might be reasonable to take actions which prevent true but subtle statements like "drug had similar side-effects to a placebo" from misleading laymen.
amund 14y ago
is this like saying: we use the metric system (small print: but our 0 cm point starts at 50 cm)?
brunorsini 14y ago
This reminded me of a very good Wired article from a couple of years ago, "Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why" - http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo...
adcoelho 14y ago
This is not by any means my field of study but i do agree that placebo components should always be disclosed in order to turn these kind of tests more transparent. However, how can we prove that something is 100% biologically inert? We can't account for all the unknown effects, is there any such 'ingredient'? I guess that at least the used placebo should be proven to not affect directly anything directly related to the hypothesis.
- rxmatic 14y ago
  It doesn't appear that anyone actually knows about the field here as this is really a non-issue for a simple reason (I chose you to reply to because you were at the bottom). First of all, most immporant studies don't use a placebo because it would unethical when there are standard treatments out there already and you have to show that your new drug is just as good or better than those treatments (the proper terms are supperior vs. non-inferior trials). But considering trials that do use a placebo - the whole point is to prove that their drug is superior to the placebo. If anything, when they design the placebo, it would have structurally similar molecules that would give the same side effects, and potentially the same results <-- which is key. A research DOES NOT WANT the placebo to do as well as their drug. The placebo can only hurt their results, not help them cheat. You could also argue that since it's not regulated, maybe the active component does actual harm to make the test drug look better! No. There are too many studies showing what the controlled group should look like (whether they are on a placebo or on nothing at all).
abtinf 14y ago
Having worked in the pharma industry, this article is complete bullshit. For double and triple blind (the third blind comes from not even the pharma company knowing the blinding details until after the trial) placebo design is an extraordinarily complex undertaking. A placebo must match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects. Any material difference in any of these categories renders the trial completely and totally meaningless, because at a minimum it unblinds the doctors on the ground. Pointing out a few random oversights out of the thousands of clinical trials that occur every year is not proof of evil on the part of pharma; it is a testament to the care that goes into their design. It represents a defect rate virtually unmatched in any other industry. But sure, go ahead and advocate irresponsible alarmism over a non-issue, as if though drug trials aren't already expensive enough, retarding scientific progress and costing millions of lives from drugs that would have been otherwise developed.
- CodeMage 14y ago
  I encourage you to post that in the comments on the blog itself. There are already comments saying "thank you for this" and "placebos should be regulated" and whatnot. Maybe I'm overly optimistic, but I believe it would be useful to have your comment close to the article text (instead of having to scroll down) to provide balance.
- hellerbarde 14y ago
  I was about to write something similar. Thanks for formulating it so eloquently. I think it's this part that trips up some people: > [...] at a minimum it unblinds the doctors on the ground. It's very important that the person administering the drug/monitoring the patient can not tell the difference.
  - abtinf 14y ago
    The effects of unblinded doctors can be catastrophic and might not even be discovered. There was one study where a drug was designed to improve motor response in patients with retarded motor skills. The doctors had found a way to determine which patient was receiving which drug. So when it came time for the doctors to measure efficacy of the drug, they would do the motor skills test. If the patient was on the actual drug, and didn't show improvement, the doctors had a tendency to say things like "Well, that can't be right. Let me run the test again." Disaster. Hundred million dollar trial down the toilet.
refurb 14y ago
This seems like a ridiculous blog post. Only 6% of clinical studies list what their placebo was, so the conclusion from that is that there is a concerted effort by drug companies to unscrupulously modified the outcomes of their studies by choosing biologically active placebos. That's a bit of a stretch. Typically what is done for a study is that drug company will manufacture the drug for the study in tablet form, complete with fillers and binders (inert ingredients used to make the pill). Then they will manufacture the same tablet without the active ingredient. The drug has to be identical in shape and color or else the study isn't really blinded, physicians could tell that patients were getting two different drug. That's the reason why drug companies make their own placebos. Also, the example of using olive oil instead of clofibrate has two possible explanations: 1) clofibrate is soluble in olive oil so they likely gave one set of patients clofibrate +olive oil and the other just olive oil (negating the effect of olive oil) OR the study was just poorly done (yes it happens) and it would be obviously to anyone familiar with clinical trials (including the people at the FDA). I could go on, but it doesn't really seem necessary. The article speaks for itself.
- pygy_ 14y ago
  Not playing in the conspiracy here, but the lack of transparency is concerning. I know the weight and complexity of the process of designing a clinical study, and I don't doubt that, in most cases, the placebos are well crafted. However, I'm sure that, in some cases there are oversights in the placebo choice (we do make mistakes), and we don't know which ones. There are also big financial stakes, and pharmaceutic firms are known to cheat while attempting to bring drugs to the market. The burial of negative studies come to mind.
- xenophanes 14y ago
  They should list placebo ingredients after the trial is done so it's possible to duplicate the trial and get the same results, right? If you don't provide enough information in your paper to repeat the experiment (and get the same results!!), then it's not good science. Good scientific studies need to be repeatable and need to provide enough information to do it. And even if people don't want to repeat the full experiment, being able to review the details of how it was done will help them spot mistakes. You can't have things like "peer review" without saying what you did. So this is a serious problem, even if the rest is breathless hype.
DanBC 14y ago
Ben Goldacre says that testing against placebo is sub-optimal. You're testing that a medication is better than nothing. What you want is a medication that tests better than whatever we're currently using. I don't know how that fits in with blinding everyone involved. As abtinf and refurb mention, designing placebo is a difficult process. And you don't need to include anything to create side-effects; people taking sugar pills will happily report having a range of side effects.
- quasque 14y ago
  "What you want is a medication that tests better than whatever we're currently using." This is also done, depends on the trial. For example, new vaccines are often tested against the existing one(s).
trotsky 14y ago
This blog seems to be rather senselessly hyperbolic and misleading. For example, it attributes an anecdote in which HIV patients are "dropping like flies" due to lactose intolerance to the research paper it cites. According to other sources [1] [2] the paper actually discusses a situation in which cancer patients were administered a lactose placebo in which the author speculates their predisposition towards lactose intolerance could have influenced the study. The gap between the two situations could hardly be larger. Certain placebos, they add, may skew results in favor of the active drug. The researchers referenced a trial for a drug used to treat anorexia linked with cancer in which a lactose placebo was used. Since lactose intolerance is common among cancer patients, the fact that some suffered stomach problems from the placebo may have made the actual drug look more beneficial. [1] http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-20101018 http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-... [2] https://en.wikipedia.org/wiki/Placebo-controlled_studies#Placebo_ingredients https://en.wikipedia.org/wiki/Placebo-controlled_studies#Pla...
oneandoneis2 14y ago
His cited example of a placebo that could skew data is olive oil, which by reducing heart disease would make the drug appear less effective than it might actually be. Pointing out a study where the pharma company might have used a placebo that made their drug harder to approve is hardly in keeping with the insinuation that they're using placebos for "disturbing" ends. Seems more like a case of "throw all the mud and hope some of it sticks" to me. Sorry.
- gwern 14y ago
  More importantly: if the tested drug can't beat olive oil on the very thing that the drug is meant to treat, then why should it be approved at all? (Drugs should be tested against the best existing alternative treatment, not merely a placebo. We are not interested in whether a new drug has a non-zero effect - but whether it is an improvement on the state of the art in some way.)
  - kragen 14y ago
    It might be an improvement on the state of the art in some other way. For example, a new antibiotic might be less effective than existing antibiotics, but have no cross-resistance with them and therefore be useful in treating antibiotic-resistant strains in the future (the magainin case), or a new antipsychotic might be less effective than existing antipsychotics for average patients, but more effective or less damaging for a few. Finally, you might be able to get synergistic effects by combining the drug with the best existing alternative treatment.
- lwat 14y ago
  Also: The placebo effect is stronger if the placebo used has side effects. Again this works AGAINST drug companies.
hermannj314 14y ago
From the article: It's inconceivable (to me, at least) that there are no laws requiring drug companies to list placebo ingredients. From CFR 21 Part 312.23 (a)(7)(iv)(c): A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial. [is required to be supplied for an Investigational New Drug Application] What is the difference? It seems the law clearly states that for new drugs, you must list the composition of your placebo to the FDA. It would seem the article is mistaken. I am not a lawyer nor do I work in the pharmaceutical industry. I just did a google search for "placebo composition site:fda.gov"
alayne 14y ago
The blog title is "Are Placebos Really Sugar Pills?". Was "Or Something Worse?" editorialized on? The thrust of the article isn't that placebos are bad, it's that they are inert and not regulated or reported on consistently.
tokenadult 14y ago
It appears that a lot of participants on Hacker News are interested in the role of placebos in treatment trials. I have some recommendations for background articles on the use of placebos in clinical trials and the pitfalls sometimes encountered in interpreting results from such trials. The articles are all by expert authors who practice frequently writing on this topic for general readers. August 2009 "The Rise of Placebo Medicine" by Steven Novella, M.D. http://www.sciencebasedmedicine.org/index.php/the-rise-of-placebo-medicine/ http://www.sciencebasedmedicine.org/index.php/the-rise-of-pl... December 2010 "Placebo Effects without Deception? Well, Not Exactly" by David Gorski, M.D. http://www.sciencebasedmedicine.org/index.php/placebo-effects-without-deception-well-not-exactly/ http://www.sciencebasedmedicine.org/index.php/placebo-effect... January 2013 "Is acupuncture as effective as antidepressants? Part 2. Blinding readers who try to get an answer" by James Coyne, Ph.D. http://www.sciencebasedmedicine.org/index.php/is-acupuncture-as-effective-as-antidepressants-part-2-blinding-readers-who-try-to-get-an-answer/ http://www.sciencebasedmedicine.org/index.php/is-acupuncture... There are many more good articles about placebos and how they are used in clinical trials on the site where these articles come from. The issue the blogger whose post is kindly submitted here seems so upset about is simply an issue of making a placebo (sham) treatment indistinguishable from the treatment under investigation, so that doctors and patients are properly "blinded" during the trial. Another comment already posted here on HN has pointed out that the FDA does oversee what ingredients are put into placebos, whether or not those detailed ingredients are published in a peer-reviewed research study. The blogger's concerns are legitimate, but not proportionate to the actual problem. Disclosure: I have been a subject of FDA-regulated medical trials. I was very impressed by thoroughness of data collection in those trials, and by my inability to distinguish whether I was receiving placebo or genuine medicine in one of those trials. My oldest son, now a hacker for a start-up, had work experience while in college at a medical device company, and he was impressed that every line of computer code he wrote during his summer job was reviewed line-by-line by FDA computer scientists as part of the review process for the medical device he worked on.
- guelo 14y ago
  It makes no sense that the FDA receives extra information that is not available to peer reviewers. Why would that be?
kuenx 14y ago
http://imgur.com/a/7Vfnc http://imgur.com/a/7Vfnc Here are some Alzheimer placebo samples (pictures) from Pfizer, handed out to doctors in Switzerland. Sorry for the bad quality. Pictures taken with a phone.
rdl 14y ago
It would be interesting to do placebo vs. placebo trials (telling patient A he's getting a specific drug and giving him a placebo instead, and telling patient B he's getting another drug which treats the same condition, and also giving him a placebo). i.e. would you subjectively report more pain relief when given ibuprofen (placebo) vs. vicodin (placebo). But, pesky IRBs :(

471 points by techdog 14y ago

acchow 14y ago

As an aside, sugars aren't biologically inert either.

Florin_Andrei 14y ago
So, is there anything that could be said to be biologically inert in any and every scenario?
- cotsuka 14y ago
  Chalk?
  - josscrowcroft 14y ago
    Calcium, surely..
    - masklinn 14y ago
      Calcium can interact with a number of other chemicals, potentially negatively (for the surrounding organism). Although doses are probably important in judging that. http://en.wikipedia.org/wiki/Calcium_metabolism#Interaction_with_other_chemicals http://en.wikipedia.org/wiki/Calcium_metabolism#Interaction_...
  - masklinn 14y ago
    Cellulose as well? Dicalcium phosphate is also a common tablet filler, though I don't know if it's biologically inactive.
  - ahi 14y ago
    It has antacid properties.
- ahi 14y ago
  Probably not, but disclosure of placebo ingredients would be enough to determine if it was a wise choice for a particular study.
- user24 14y ago
  Gold?
  - Locke1689 14y ago
    Gold allergy.
- trotsky 14y ago
  A quote from the press release about the paper the OP cites: But, according to the paper's author, Beatrice Golomb, MD, PhD, associate professor of medicine at the University of California, San Diego School of Medicine, this standard has a fundamental problem, "there isn't anything actually known to be physiologically inert." http://www.sciencedaily.com/releases/2010/10/101018174335.htm http://www.sciencedaily.com/releases/2010/10/101018174335.ht...
- marvin 14y ago
  Cellulose? Diamond? Glass? Ceramics?
  - acchow 14y ago
    I believe glass should work. Maybe teflon?
sek 14y ago
Everybody consumes a huge amount of sugar every day, so the pill is not even measurable compared to your normal intake. So on average the effect of this small amount of sugar disappears.
driverdan 14y ago
Unless you're studying something related to blood sugar, insulin, etc or the user has a condition impacted by sugar, such as diabetes, a small amount of sugar (pills would contain 100-1000mg) isn't going to have any impact.

cooldeal 14y ago

Aren't the side effects mimicked so that participants won't see the lack of them and then know that they're taking the placebo which will defeat the double blind study? For example, if you're testing fish oil, you wouldn't use a sugar pill since it's easy to know what you're taking by looking at it. You would use something like olive oil.

newishuser 14y ago
There are certainly ways to simulate fish oil with biologically inert ingredients.
- pmelendez 14y ago
  I think you're missing the point. He was talking about this section of the article: >That way, of course, they can say things in their ads like "[drug name] has a low occurrence of side effects, such as dry mouth, which occurred about as often as they did with placebo." cooldeal point is that you need to mimic the side effects to make the control group believable. Whether it is needed to use inert components or not would depend on the nature of the drug in test.
- kragen 14y ago
  There are? What do you have in mind? If you use mineral oil or Olean, you get diarrhea as a side effect in doses of more than a few grams per day.
pygy_ 14y ago
Indeed. It is well known that SSRIs studies were biased because of this, because SSRIs have a lot of early side effects, which break the blinding. Knowing that you're in the treatment branch increases the placebo effect. That being said, the opacity of the manufacture process is concerning. Studies with active placebos should have a third branch with inert placebos, to assess the incidence of side effects.
- Locke1689 14y ago
  That presents massive ethical issues. One would have to knowingly not give subjects a drug that we know helps them (i.e., the current standard of care).

newishuser 14y ago

What this article leads me to think is that we need to legally protect the word placebo. It seems grossly misleading to use the word placebo to describe non biologically inert ingredients. To do so is to lie and nothing more.

wiredfool 14y ago
Just look for homeopathic remedies then. Guaranteed not to have any active ingredients.
- joshuacc 14y ago
  That's not strictly true. Homeopathic remedies do often include small amounts of alcohol or sugar.
  - hellerbarde 14y ago
    unless it's homeopathic alcohol :P http://homeopathicvodka.com/ http://homeopathicvodka.com/
- plorkyeran 14y ago
  Not everything that claims to be homeopathic actually is. One example is Traumeel. If you look at their ingredients ( http://www.traumeel.us/Products/ProductDetail.aspx?id=1901000 http://www.traumeel.us/Products/ProductDetail.aspx?id=190100... ), there's enough active ingredients that are only 1X diluted that the total is over .5% active. I assume it's just labeled as homeopathic because they failed to fake some clinical trials to get FDA approval (or didn't even try), but maybe it's actually an effective marketing choice.
jessriedel 14y ago
Actually, I think "Placebo" has always meant "a thing used to make not taking a drug an indistinguishable experience to taking it" (which, it turns out upon reflection, requires it to inflict side effects). Inertness is just a popular misconception. That said, I think capitalizing on that misconception is wrong and that it might be reasonable to take actions which prevent true but subtle statements like "drug had similar side-effects to a placebo" from misleading laymen.

amund 14y ago

is this like saying: we use the metric system (small print: but our 0 cm point starts at 50 cm)?

brunorsini 14y ago

This reminded me of a very good Wired article from a couple of years ago, "Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why" - http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo...

adcoelho 14y ago

This is not by any means my field of study but i do agree that placebo components should always be disclosed in order to turn these kind of tests more transparent. However, how can we prove that something is 100% biologically inert? We can't account for all the unknown effects, is there any such 'ingredient'? I guess that at least the used placebo should be proven to not affect directly anything directly related to the hypothesis.

rxmatic 14y ago
It doesn't appear that anyone actually knows about the field here as this is really a non-issue for a simple reason (I chose you to reply to because you were at the bottom). First of all, most immporant studies don't use a placebo because it would unethical when there are standard treatments out there already and you have to show that your new drug is just as good or better than those treatments (the proper terms are supperior vs. non-inferior trials). But considering trials that do use a placebo - the whole point is to prove that their drug is superior to the placebo. If anything, when they design the placebo, it would have structurally similar molecules that would give the same side effects, and potentially the same results <-- which is key. A research DOES NOT WANT the placebo to do as well as their drug. The placebo can only hurt their results, not help them cheat. You could also argue that since it's not regulated, maybe the active component does actual harm to make the test drug look better! No. There are too many studies showing what the controlled group should look like (whether they are on a placebo or on nothing at all).

abtinf 14y ago

Having worked in the pharma industry, this article is complete bullshit. For double and triple blind (the third blind comes from not even the pharma company knowing the blinding details until after the trial) placebo design is an extraordinarily complex undertaking. A placebo must match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects. Any material difference in any of these categories renders the trial completely and totally meaningless, because at a minimum it unblinds the doctors on the ground. Pointing out a few random oversights out of the thousands of clinical trials that occur every year is not proof of evil on the part of pharma; it is a testament to the care that goes into their design. It represents a defect rate virtually unmatched in any other industry. But sure, go ahead and advocate irresponsible alarmism over a non-issue, as if though drug trials aren't already expensive enough, retarding scientific progress and costing millions of lives from drugs that would have been otherwise developed.

CodeMage 14y ago
I encourage you to post that in the comments on the blog itself. There are already comments saying "thank you for this" and "placebos should be regulated" and whatnot. Maybe I'm overly optimistic, but I believe it would be useful to have your comment close to the article text (instead of having to scroll down) to provide balance.
hellerbarde 14y ago
I was about to write something similar. Thanks for formulating it so eloquently. I think it's this part that trips up some people: > [...] at a minimum it unblinds the doctors on the ground. It's very important that the person administering the drug/monitoring the patient can not tell the difference.
- abtinf 14y ago
  The effects of unblinded doctors can be catastrophic and might not even be discovered. There was one study where a drug was designed to improve motor response in patients with retarded motor skills. The doctors had found a way to determine which patient was receiving which drug. So when it came time for the doctors to measure efficacy of the drug, they would do the motor skills test. If the patient was on the actual drug, and didn't show improvement, the doctors had a tendency to say things like "Well, that can't be right. Let me run the test again." Disaster. Hundred million dollar trial down the toilet.

refurb 14y ago

This seems like a ridiculous blog post. Only 6% of clinical studies list what their placebo was, so the conclusion from that is that there is a concerted effort by drug companies to unscrupulously modified the outcomes of their studies by choosing biologically active placebos. That's a bit of a stretch. Typically what is done for a study is that drug company will manufacture the drug for the study in tablet form, complete with fillers and binders (inert ingredients used to make the pill). Then they will manufacture the same tablet without the active ingredient. The drug has to be identical in shape and color or else the study isn't really blinded, physicians could tell that patients were getting two different drug. That's the reason why drug companies make their own placebos. Also, the example of using olive oil instead of clofibrate has two possible explanations: 1) clofibrate is soluble in olive oil so they likely gave one set of patients clofibrate +olive oil and the other just olive oil (negating the effect of olive oil) OR the study was just poorly done (yes it happens) and it would be obviously to anyone familiar with clinical trials (including the people at the FDA). I could go on, but it doesn't really seem necessary. The article speaks for itself.

pygy_ 14y ago
Not playing in the conspiracy here, but the lack of transparency is concerning. I know the weight and complexity of the process of designing a clinical study, and I don't doubt that, in most cases, the placebos are well crafted. However, I'm sure that, in some cases there are oversights in the placebo choice (we do make mistakes), and we don't know which ones. There are also big financial stakes, and pharmaceutic firms are known to cheat while attempting to bring drugs to the market. The burial of negative studies come to mind.
xenophanes 14y ago
They should list placebo ingredients after the trial is done so it's possible to duplicate the trial and get the same results, right? If you don't provide enough information in your paper to repeat the experiment (and get the same results!!), then it's not good science. Good scientific studies need to be repeatable and need to provide enough information to do it. And even if people don't want to repeat the full experiment, being able to review the details of how it was done will help them spot mistakes. You can't have things like "peer review" without saying what you did. So this is a serious problem, even if the rest is breathless hype.

DanBC 14y ago

Ben Goldacre says that testing against placebo is sub-optimal. You're testing that a medication is better than nothing. What you want is a medication that tests better than whatever we're currently using. I don't know how that fits in with blinding everyone involved. As abtinf and refurb mention, designing placebo is a difficult process. And you don't need to include anything to create side-effects; people taking sugar pills will happily report having a range of side effects.

quasque 14y ago
"What you want is a medication that tests better than whatever we're currently using." This is also done, depends on the trial. For example, new vaccines are often tested against the existing one(s).

trotsky 14y ago

This blog seems to be rather senselessly hyperbolic and misleading. For example, it attributes an anecdote in which HIV patients are "dropping like flies" due to lactose intolerance to the research paper it cites. According to other sources [1] [2] the paper actually discusses a situation in which cancer patients were administered a lactose placebo in which the author speculates their predisposition towards lactose intolerance could have influenced the study. The gap between the two situations could hardly be larger. Certain placebos, they add, may skew results in favor of the active drug. The researchers referenced a trial for a drug used to treat anorexia linked with cancer in which a lactose placebo was used. Since lactose intolerance is common among cancer patients, the fact that some suffered stomach problems from the placebo may have made the actual drug look more beneficial. [1] http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-20101018 http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-... [2] https://en.wikipedia.org/wiki/Placebo-controlled_studies#Placebo_ingredients https://en.wikipedia.org/wiki/Placebo-controlled_studies#Pla...

oneandoneis2 14y ago

His cited example of a placebo that could skew data is olive oil, which by reducing heart disease would make the drug appear less effective than it might actually be. Pointing out a study where the pharma company might have used a placebo that made their drug harder to approve is hardly in keeping with the insinuation that they're using placebos for "disturbing" ends. Seems more like a case of "throw all the mud and hope some of it sticks" to me. Sorry.

gwern 14y ago
More importantly: if the tested drug can't beat olive oil on the very thing that the drug is meant to treat, then why should it be approved at all? (Drugs should be tested against the best existing alternative treatment, not merely a placebo. We are not interested in whether a new drug has a non-zero effect - but whether it is an improvement on the state of the art in some way.)
- kragen 14y ago
  It might be an improvement on the state of the art in some other way. For example, a new antibiotic might be less effective than existing antibiotics, but have no cross-resistance with them and therefore be useful in treating antibiotic-resistant strains in the future (the magainin case), or a new antipsychotic might be less effective than existing antipsychotics for average patients, but more effective or less damaging for a few. Finally, you might be able to get synergistic effects by combining the drug with the best existing alternative treatment.
lwat 14y ago
Also: The placebo effect is stronger if the placebo used has side effects. Again this works AGAINST drug companies.

hermannj314 14y ago

From the article: It's inconceivable (to me, at least) that there are no laws requiring drug companies to list placebo ingredients. From CFR 21 Part 312.23 (a)(7)(iv)(c): A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial. [is required to be supplied for an Investigational New Drug Application] What is the difference? It seems the law clearly states that for new drugs, you must list the composition of your placebo to the FDA. It would seem the article is mistaken. I am not a lawyer nor do I work in the pharmaceutical industry. I just did a google search for "placebo composition site:fda.gov"

alayne 14y ago

The blog title is "Are Placebos Really Sugar Pills?". Was "Or Something Worse?" editorialized on? The thrust of the article isn't that placebos are bad, it's that they are inert and not regulated or reported on consistently.

tokenadult 14y ago

It appears that a lot of participants on Hacker News are interested in the role of placebos in treatment trials. I have some recommendations for background articles on the use of placebos in clinical trials and the pitfalls sometimes encountered in interpreting results from such trials. The articles are all by expert authors who practice frequently writing on this topic for general readers. August 2009 "The Rise of Placebo Medicine" by Steven Novella, M.D. http://www.sciencebasedmedicine.org/index.php/the-rise-of-placebo-medicine/ http://www.sciencebasedmedicine.org/index.php/the-rise-of-pl... December 2010 "Placebo Effects without Deception? Well, Not Exactly" by David Gorski, M.D. http://www.sciencebasedmedicine.org/index.php/placebo-effects-without-deception-well-not-exactly/ http://www.sciencebasedmedicine.org/index.php/placebo-effect... January 2013 "Is acupuncture as effective as antidepressants? Part 2. Blinding readers who try to get an answer" by James Coyne, Ph.D. http://www.sciencebasedmedicine.org/index.php/is-acupuncture-as-effective-as-antidepressants-part-2-blinding-readers-who-try-to-get-an-answer/ http://www.sciencebasedmedicine.org/index.php/is-acupuncture... There are many more good articles about placebos and how they are used in clinical trials on the site where these articles come from. The issue the blogger whose post is kindly submitted here seems so upset about is simply an issue of making a placebo (sham) treatment indistinguishable from the treatment under investigation, so that doctors and patients are properly "blinded" during the trial. Another comment already posted here on HN has pointed out that the FDA does oversee what ingredients are put into placebos, whether or not those detailed ingredients are published in a peer-reviewed research study. The blogger's concerns are legitimate, but not proportionate to the actual problem. Disclosure: I have been a subject of FDA-regulated medical trials. I was very impressed by thoroughness of data collection in those trials, and by my inability to distinguish whether I was receiving placebo or genuine medicine in one of those trials. My oldest son, now a hacker for a start-up, had work experience while in college at a medical device company, and he was impressed that every line of computer code he wrote during his summer job was reviewed line-by-line by FDA computer scientists as part of the review process for the medical device he worked on.

guelo 14y ago
It makes no sense that the FDA receives extra information that is not available to peer reviewers. Why would that be?

kuenx 14y ago

http://imgur.com/a/7Vfnc http://imgur.com/a/7Vfnc Here are some Alzheimer placebo samples (pictures) from Pfizer, handed out to doctors in Switzerland. Sorry for the bad quality. Pictures taken with a phone.

rdl 14y ago

It would be interesting to do placebo vs. placebo trials (telling patient A he's getting a specific drug and giving him a placebo instead, and telling patient B he's getting another drug which treats the same condition, and also giving him a placebo). i.e. would you subjectively report more pain relief when given ibuprofen (placebo) vs. vicodin (placebo). But, pesky IRBs :(