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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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June 21, 2004

Primum Non Nocere, Eh?

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Posted by Derek

The placebo effect is a real problem in some clinical trials. It varies, but in things like antidepressants it's a major factor (while with, say, pancreatic cancer it doesn't change the results too much.) In a given sample of depressed patients, there are a fair number of people (20 or thirty percent) who will respond if you give them 50 milligrams of confectioner's sugar which they truly believe to be an efficacious drug.

Of course, the majority will respond as if you'd given them, well, confectioner's sugar, but that group of placebo responders will blow your statistical workup to pieces. This is one of the reasons that you see multiple trials for antidepressants, because the trials themselves often just produce noisy data. Of course, one way to interpret this is that the antidepressants themselves are fairly worthless. That's a tempting conclusion, and for some people, they clearly don't do much good. But you can find others that truly appear to have been helped. Depressed patients, even ones who may look and act similarly, are clearly a heterogeneous population.

What if those strong placebo-responders could be weeded out of the patient population before you even started the clinical trial? This question is a good test of a person's attitude toward the drug industry. Many folks will hear that idea and cry "Fraud! Stacking the deck!" But think about it. If you could find the people who will improve when given a sugar pill, then you could pull them aside and just go ahead and give 'em the sugar pill. Hey, it's effective therapy, and that's what counts, right? And they'll miss out on the side effects of the antidepressant drugs themselves, and every drug has side effects at some level - every single one.

Meanwhile, once those folks have been sorted out, you're left with a cohort of patients who need all the help they can get, and now you're in a statistical position to see if you can really provide any. As far as I can see, everyone comes out ahead.

It turns out that there may be ways to see who's a strong placebo effect candidate and who isn't. There have been several studies in the last few years that show some real correlations in brain activity during placebo situations, and this has lead to the idea of a test for it.

If this goes on, though, there could be some interesting developments. What if everyone becomes aware of the test to see if you're going to get a placebo? Will the responders still respond if they thing there's a reasonable chance that they didn't get a "real" drug? I think that what we'll need to do is present the test as a standard procedure, to help figure out which therapy would work the best - not a method to see if you get a drug or not, but a method to see which drug you should get. That should keep things working.

Comments (5) + TrackBacks (0) | Category: Clinical Trials


1. Peter North on June 22, 2004 12:35 AM writes...

Don't knock sugar. My dad was Director of Research for Tate & Lyle (50% of the UK Sugar Industry). Dad told the story of his counter part in Lousiana (Dennis Dickinson). Dennis was always scared that sugar would be moved from Food & Agriculture regulation to FDA regulation because it gave kids such an effective high. You can tell me what would happen to the price.

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2. SP on June 22, 2004 10:58 AM writes...

But the placebo can have side effects as well- "side effects were similar to sugar pill."

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3. kevin white on June 22, 2004 11:46 AM writes...

I'll be really annoyed if my parents have to start smuggling sugar from Canada.

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4. Derek Lowe on June 22, 2004 12:39 PM writes...

The line between a food and a drug can be rather blurry, no doubt about it. I think that the problem is a misplaced Cartesian outlook, leading to unsupportable positions like: "food affect the body, not the mind. CNS drugs affect the mind, not the body."

Makes you wonder if there's such a thing as a properly placed Cartesian worldview, actually.

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5. Richard Dietzel on June 24, 2004 9:32 PM writes...

I read a summary of a study some years ago that purported to show that Doctors had the strongest placebo response in studies. I always told fellow patients this was for two reasons, Doctors know that drugs can work and their egos don't allow them to believe they wouldn't get the active compound.

It may be that the fact of testing for Placebo Sensitivity will effect Placebo Sensitivity or PS may be ingrained, like genetic optimism.

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