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This was discussed 2 years ago here: http://www.doctorslounge.com/index.php/news/pb/14946

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. :)

Journal articles are short because journals have limited space. In the year 2013, this is no longer a relevant issue. Just add appendices, online only if necessary, covering placebo composition and other details so that people who want to dive deep can.

I'm a little late responding to this, but there are good points here. It seems like a good compromise might be to have the FDA release the details of the trials / placebo ingredients. That way they can be mapped to the studies that used them (assuming the studies don't just start documenting them). That might be happening already, I don't work in the field, so I don't know.

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

> But the blog post says "Hey! Drug companies are trying to pull a fast on all of you!…"

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.

That's not all the blog post says. Your implicit summary is inaccurate.

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.

Everything else aside, it should be illegal to advertise that your drug "has similar side-effects to placebo" if the placebo has active ingredients deliberately intended to cause the side effects.

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.

Their takeaway is the same one I got, so perhaps you are reading it differently than we are? The piece I read was alarmed that a very important detail can only be found in 8% of the studies they examined and wondered what's up with that.

"and later suggests that active placebos be outlawed."

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..."

He doesn't simply call for active placebos to be outlawed. He lists several problems with the current system and then says:

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?

I'm not sure we read the same article. The one I read said, and this is the whole graf:

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?

Why do blind studies need the regulation on active placebos to be non rigorous?

Who are you arguing with? Surely not me. But the case you're making isn't the case the blog post made. The blog post suggests, with varying levels of overtness, that there is something shady about active placebos.

I'm talking about the quote you used on your comment. That quote by itself does not sound particularly outrageous or ignorant.

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

Outlawing active placebos might be a reasonable course of action?

Outlawing active placebos would actually be very foolish. Up to 90% of patients and 100% of physicians have been found to have broken blinds in trials of tricyclics, almost certainly because of the side effects. The original article is extremely weak in failing to address this... in fact, drug companies really should be adding ingredients with side effects to their placebos, but won't because it increases the complexity and reduces the statistical power of the trials they run.

Agreed, so change advertising requirements. Instead of "compared to a placebo" (which is highly misleading in this case), make the drug companies disclose side effects differently. "In clinical trials, this drug had the following incidents of side effects... An active placebo intended to cause anticipated side effects had the following incidents...."

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.

I take the sentence to mean "If there are no rigorous controls in place on active placebos, they should be outlawed" which doesn't sound unreasonable.

It's totally unreasonable; it would be saying "because we don't trust the FDA, we should unblind drug trials".

People threaten people with things that they themselves would find horrible, in order to incentivize the other party, all the time. The US budget sequestration, for example: a bunch of spending cuts none of us wanted, created with the intention of making us pick spending cuts we did want instead so that it wouldn't happen.

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.

The blog post author may have used the idea of outlawing active placebos as a "door in the face" to make regulating them seem more palatable. At the least, it seems koide is interpreting the second suggestion as having more weight, while you are focusing on the first.

I don't think it would be a reasonable course of action. However, I do think that as long as they are relatively unregulated, a much better approach would be to limit inserts and advertising descriptions on the incidents of side effects to absolute proportions, not comparing side effect proportions to those on active placebos intended to mimic expected side effects.

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

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?

> And that will skew the results of the drug tests, too,

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.

>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.

Why not?

because people have olive oil already...

Well, you are assuming they cannot be combined.

That would be a completely different study. You can't make any claims about the effect of a&b if you've only studied a|b.

"This "missing information" is available to the people that matter (the FDA)." - That's right, I'm just too unimportant and stupid to be trusted to look at this stuff, also when the issue a lot of people are having is not being able to trust big pharma and the FDA, well hiding stuff isn't going to fix that.

Yes, I was being a bit dramatic for impact.