Are Placebos Really Sugar Pills? • Hacker News Board

Re: Are Placebos Really Sugar Pills?

#71

Post by tptacek » Wed, Jan 30, 2013, 6:18 PM UTC

ahoyhere wrote: post #48

abtinf wrote: post #21

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 diffe…

Why does the placebo complexity make a call for regulation and study disclosure "utter bullshit"?

Again: it didn't simply call for "regulation" and "disclosure". It overtly accused pharma companies of using active placebos for marketing purposes, of haphazardly endangering participants in trials, and then later suggested that the whole concept of active placebos might reasonably be outlawed.

The post we're commenting on made a series of outlandishly ignorant assertions.

That there are reasonable challenges we might make to the way active placebos are handled does not make the article better. You're a great writer. Maybe you should write a good article on the perils of undisclosed/underdisclosed active placebos? Because this particular article doesn't appear to be good.

Re: Are Placebos Really Sugar Pills?

#72

Post by BHSPitMonkey » Wed, Jan 30, 2013, 6:19 PM UTC

pygy_ wrote: post #23

cooldeal wrote: post #3

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.

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.

Perhaps the real problem the article should hone in on is that drug companies are (allegedly?) permitted to compare side effect rates to that of the "placebos", when the public will undoubtedly not be aware that the placebos used were manufactured to provide those same side effects.

Re: Are Placebos Really Sugar Pills?

#73

Post by jessriedel » Wed, Jan 30, 2013, 6:21 PM UTC

crpatino wrote: post #59

abtinf wrote: post #21

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 diffe…

While the article might have pulled a few cheap shots at pharma companies, the point stands. We need disclosure of this incredibly complex placebo matching methodology (for lack of a better term), at minimum because the experiments cannot be replicated by a third party without it. Another reason for disclosure is the ethical risk assessment. What is to prevent a misguided executive from arranging a placebo with minim…

Do we know if it hasn't been disclosed in FDA filings (which are way more detailed), or just that it was disclosed in these research articles? Journal articles are meant to be terse for readability, and standard placebo techniques are just the sort of thing I would expect to be left out.

Re: Are Placebos Really Sugar Pills?

#74

Post by gwern » Wed, Jan 30, 2013, 6:21 PM UTC

oneandoneis2 wrote: post #53

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…

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.)

Re: Are Placebos Really Sugar Pills?

#75

Post by sethev » Wed, Jan 30, 2013, 6:22 PM UTC

ahoyhere wrote: post #61

tptacek wrote: post #55

Earlier quoted context omitted.

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.

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 rea…

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?

Re: Are Placebos Really Sugar Pills?

#76

Post by warmwaffles » Wed, Jan 30, 2013, 6:30 PM UTC

tedunangst wrote: post #58

jat850 wrote: post #31

Earlier quoted context omitted.

Is it not possible that, via whatever mechanism placebo drugs have positive intended effects, that they could also cause side effects?

Placebo effect is not a 100% effective substitute for the real deal. If the drug makes you pee more, you could convince yourself of that. If the drug makes your pee turn purple, that'd be harder to achieve just by willing it to happen.

This is a straw man example. Headaches or sinus pressure may be a better way to explain your point.

Re: Are Placebos Really Sugar Pills?

#77

Post by samstave » Wed, Jan 30, 2013, 6:32 PM UTC

abtinf wrote: post #21

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 diffe…

So didn't you just state that a placebo needs to cause side effects?

Doesn't that mean that it's poison by nature if said side effects are negative?

Screw wanting to take part in that.

"Here's a pill that will cause oily discharge and nothing else" Yum!

Re: Are Placebos Really Sugar Pills?

#78

Post by samstave » Wed, Jan 30, 2013, 6:32 PM UTC

abtinf wrote: post #21

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 diffe…

So didn't you just state that a placebo needs to cause side effects?

Doesn't that mean that it's poison by nature if said side effects are negative?

Screw wanting to take part in that.

"Here's a pill that will cause oily discharge and nothing else" Yum!

Re: Are Placebos Really Sugar Pills?

#79

Post by samstave » Wed, Jan 30, 2013, 6:32 PM UTC

abtinf wrote: post #21

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 diffe…

So didn't you just state that a placebo needs to cause side effects?

Doesn't that mean that it's poison by nature if said side effects are negative?

Screw wanting to take part in that.

"Here's a pill that will cause oily discharge and nothing else" Yum!

Re: Are Placebos Really Sugar Pills?

#80

Post by starpilot » Wed, Jan 30, 2013, 6:32 PM UTC

Locke1689 wrote: post #63

pygy_ wrote: post #23

Earlier quoted context omitted.

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.

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).

There are no ethical issues.

1. Study participants are told that some of them will receive a "sham" (placebo) treatment. Participation is voluntary.

2. It is not known whether the drug they are testing is effective or comparable to the current standard of care. Determining that is the purpose of the study.