Are Placebos Really Sugar Pills?

Having worked in the pharma industry, this article is complete bullshit.<p>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 <i>completely and totally meaningless</i>, because at a minimum it unblinds the doctors on the ground.<p>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.<p>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.

This seems like a ridiculous blog post.<p>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.<p>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.<p>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).<p>I could go on, but it doesn't really seem necessary. The article speaks for itself.

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.<p>August 2009 "The Rise of Placebo Medicine" by Steven Novella, M.D.<p><a href="http://www.sciencebasedmedicine.org/index.php/the-rise-of-placebo-medicine/" rel="nofollow">http://www.sciencebasedmedicine.org/index.php/the-rise-of-pl...</a><p>December 2010 "Placebo Effects without Deception? Well, Not Exactly" by David Gorski, M.D.<p><a href="http://www.sciencebasedmedicine.org/index.php/placebo-effects-without-deception-well-not-exactly/" rel="nofollow">http://www.sciencebasedmedicine.org/index.php/placebo-effect...</a><p>January 2013 "Is acupuncture as effective as antidepressants? Part 2. Blinding readers who try to get an answer" by James Coyne, Ph.D.<p><a href="http://www.sciencebasedmedicine.org/index.php/is-acupuncture-as-effective-as-antidepressants-part-2-blinding-readers-who-try-to-get-an-answer/" rel="nofollow">http://www.sciencebasedmedicine.org/index.php/is-acupuncture...</a><p>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.<p>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.

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.<p>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.<p>Seems more like a case of "throw all the mud and hope some of it sticks" to me. Sorry.

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.<p><i>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.</i><p>[1] <a href="http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-20101018" rel="nofollow">http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-...</a><p>[2] <a href="https://en.wikipedia.org/wiki/Placebo-controlled_studies#Placebo_ingredients" rel="nofollow">https://en.wikipedia.org/wiki/Placebo-controlled_studies#Pla...</a>

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" - <a href="http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all" rel="nofollow">http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo...</a>

From the article: <i>It's inconceivable (to me, at least) that there are no laws requiring drug companies to list placebo ingredients.</i><p>From CFR 21 Part 312.23 (a)(7)(iv)(c): <i>A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial.</i> [is required to be supplied for an Investigational New Drug Application]<p>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"

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.<p>I don't know how that fits in with blinding everyone involved. As abtinf and refurb mention, designing placebo is a difficult process.<p>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.

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.<p>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.

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

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.

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.

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).<p>i.e. would you subjectively report more pain relief when given ibuprofen (placebo) vs. vicodin (placebo).<p>But, pesky IRBs :(

<a href="http://imgur.com/a/7Vfnc" rel="nofollow">http://imgur.com/a/7Vfnc</a><p>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.

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

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?<p>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.