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How Antidepressant Clinical Trial Failures Relates to the Electron Charge

As mentioned in a previous blog post (http://scienceninja.posterous.com/the-epidemic-of-mental-illness-the-illusions), careful meta-analyses of many clinical trials of commonly prescribed anti-depressants suggest that they don’t do any better than placebos, and newer trials seem to demonstrate a trend where any beneficial effects of anti-depressants over placebos is disappearing.
This controversy in psychiatry has prompted this response in the prestigious and high impact “American Journal of Psychiatry”.  What is their explanation for this failure to show efficacy over placebo in new trials?  The patients in the new trials are not really depressed, they are frauds who are looking for cash payouts to be part of clinical trials.  They give a couple of anecdotal examples.


In essence what he is saying:  These drugs really do work. we just can’t demonstrate it in clinical trials because patients lie.  Studies that give the result we want (drugs work good) are good, well designed trials.  Studies which show no effect or placebo doing better are plagued with lying patients that obscure the true efficacy and should be ignore.  Bad trial participants is the problem.  Trust us.  These drugs really do work.  We’ve shown these drugs work in clinical trials.  The good ones.  Where they show that they work.
Now perhaps a better example of what might be happening can be seen in physics, a place where we can make much more careful and exacting physical measurements with lower variability (than for example, self reported mood).  Robert Millikan developed a technique for measuring electron charge looking at falling oil drops in an electric field.  Richard Feynman explains his results and those who followed him in his essay “Cargo Cult Science” (http://www.lhup.edu/~DSIMANEK/cargocul.htm):
We have learned a lot from experience about how to handle some of the ways we fool ourselves. One example: Millikan measured the charge on an electron by an experiment with falling oil drops, and got an answer which we now know not to be quite right. It’s a little bit off, because he had the incorrect value for the viscosity of air. It’s interesting to look at the history of measurements of the charge of the electron, after Millikan. If you plot them as a function of time, you find that one is a little bigger than Millikan’s, and the next one’s a little bit bigger than that, and the next one’s a little bit bigger than that, until finally they settle down to a number which is higher. Why didn’t they discover that the new number was higher right away? It’s a thing that scientists are ashamed of–this history–because it’s apparent that people did things like this: When they got a number that was too high above Millikan’s, they thought something must be wrong–and they would look for and find a reason why something might be wrong. When they got a number closer to Millikan’s value they didn’t look so hard. And so they eliminated the numbers that were too far off, and did other things like that. We’ve learned those tricks nowadays, and now we don’t have that kind of a disease.
It is a very common phenomenon in scientific endeavors that an initially interesting finding or association can often disappear under repeated analyses.  Investigators are biased toward repeating the initial results, but as they investigate further, they semi-assymptotically converge to the true value.


2 responses to “How Antidepressant Clinical Trial Failures Relates to the Electron Charge

  1. Anonymous January 28, 2012 at 8:27 am

    I was adding a bit of rhetoric, and trying to put it in the context of the overall dialogue/debate between the statisticians and the drug producers and prescribers.

  2. Maureen January 28, 2012 at 1:00 am

    Interesting. I read the psych paper and don’t read it nearly as extremely as you do. They’re simply asking why the placebo rates are so high, not why the placebo-response rates are as high as the drug-response rates (though I guess that’s sort of implied…) They point out some lying patients, but don’t go on to say that "good" trials show that the drugs work, as you paraphrased above.They say at the end"We cannot conclude from the basis of our anecdotal experiences that placebo response rates are being significantly inflated by fraudulent volunteers. … We also urge clinicians and professional associations to encourage real patients to volunteer for clinical research."There was a Stanford Medicine magazine article a year or so ago about "professional" clinical trial participants. It was interesting and reminiscent of this.

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