When you submit a drug for approval at the FDA, you need to list in exacting detail exactly how trials were run, including how they were blinded. The ingredients and form of the placebo are critical for this.

The paper referenced in this blog post examined journal articles to determine if the composition of the placebo was reported. Journal article are notoriously lacking in details and they have to be since no one want to read an article with pages upon pages of details.

If his comment was "Hey, you guys who write papers on clinical trials, it would be awesome if you'd list the placebo composition, since I'd be more likely to believe your findings" I would say "fair point".

But the blog post says "Hey! Drug companies are trying to pull a fast on all of you! Beware of what's in your medicine cabinet" which is a completely ridiculous statement. This "missing information" is available to the people that matter (the FDA).

This is truly an example of making a mountain out of a molehill.

and here: http://pharmastrategyblog.com/2010/10/whats-in-placebos-who-...

But all three article (including the Topic) seem to focus on the Journal articles and neglect to write anything about the reports to the FDA. I'd be really interested in more info on that.

EDIT: I have no opinion nor info about the quality of the links i posted, I just found them through cursory duckduckgoing. So beware, they might both be total cranks. :)

Anyway, I found this comment useful. Thanks for replying.

Actually what it says is that placebo ingredients should be documented in studies, and regulated by the FDA. Why is that such heresy? If placebos are sugar pills, they don't need regulation. If they are designed to cause side effects, they are drugs. And that will skew the results of the drug tests, too, and as he describes in the olive oil example, not always in favor of the drug company.

The blog overtly implies that drug companies use active placebos to minimize advertised side effects, and later suggests that active placebos be outlawed.

In fact, active placebos are a requirement for drug trials, because without them, the trial can't be effectively blinded.

The claim as made by the ads indicates to the average rational person that taking the drug has no higher chance of side effects than simple sugar pills. The reasonable conclusion for anyone who would be willing to take sugar pills is that this medication is safe, when in fact it easily might not be.

And to repeat my point just made in another comment all of it based on "Over the weekend I was reading some medical studies involving placebos.....then I started to wonder..."

FDA needs to review its policies on placebos and either outlaw "active placebos" or rigorously define acceptable conditions for their use.

That's like saying "The US Govt either needs to outlaw medicines OR rigorously define acceptable conditions for their use." Which is not a statement most reasonable people would disagree with… hence the FDA. Everybody would obviously choose the second measure. It's a classic persuasion technique: give an extreme choice so the other choice will seem more reasonable. It gets attention. Nobody is going to outlaw active placebos.

As for overtly implying drug companies manipulate their results, he had a small handful of examples and one of them is a counter example where the drug company looks to be undermining its own results by using a too-good placebo (olive oil) that made its drug look useless.

Finally he raises the question: If you kick people out of the study when they improve on placebo, are you still actually testing against placebo?

How can you know, if the trials don't document what's in the placebo, and the FDA doesn't regulate it?

FDA needs to review its policies on placebos and either outlaw "active placebos" or rigorously define acceptable conditions for their use.

That seems like a profoundly ignorant argument. The article doesn't account for the need to blind studies. Why does it come across as credible to you?

You should have chosen a different line to illustrate how shady the author thinks active placebos are.

This preserves all of what you can currently get, but it frames the issue so that the average individual does not assume that an on-par comparison means all side effects are placebo effect.

The idea behind this statement is similar: if the FDA actually pre-commits to a policy saying "either we're going to figure out a huge set of requirements for publishing placebo composition data [huge hassle for us, honestly] or, if we haven't done that by January 2015, no more active placebos"--well, suddenly the drug companies are breathing down the FDA's neck to get those requirements drafted so they can comply with them before it's too late.

But these are accusations made by a man who admits he had never heard of active placebos until a few days ago. He's reading reports that are summaries of the trials and apparently concluding that since the summary doesn't include the ingredients of the placebo then they're undocumented and not regulated by the FDA. How does he know that?

No, that's the entire point of placebos. Placebos are not supposed to be absolutely nothing they are supposed to account for all manner peripheral effects and determine efficacy.

The idea is to test your treatment against something that should have no or very low effectiveness. It's fine for them to be drugs and it's fine for them to have an effect - there's a name for that: placebo effects. People tend to get this confused with the well known "the placebo effect", but that is not the only effect placebos are intended to control for.

The example you point to is dubious to me. The study seems to be working as intended: if you have a drug that doesn't work better than olive oil - you don't have a useful drug.

We're talking about a cholesterol drug here, and it's not that the drug didn't do what it was supposed to do - control cholesterol - better than olive oil; it didn't improve mortality (for a specific subgroup)...something you'd expect with cholesterol control however that doesn't mean it's not effective in it's primary objective.

In fact Clofibrate was taken off the market for precisely that reason; it's effective in lowering cholesterol but it has side effects which lead to increased mortality.

I'm all for increased transparency in placebo use; but this article seems to have done little to clear the confusion about what placebos are and what they are intended for.

Why not?

Yes, I was being a bit dramatic for impact.

According to the OP whose is (just checked) a tech evangelist at Adobe. Additionally the sum of their research is "Over the weekend I was reading some medical studies involving placebos".

What I'm seeing is that someone wrote something (the OP) and made some statements and additionally pointed to one journal article (which I'm sure only a few HN'ers have even bothered to click through and glance at.)

This is interesting to discuss and that's it (at this point at least).

"(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an "Investigational New Drug Application" (IND) including, in the following order:

...

(c ) A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial."

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRS...