Placebos Becoming More Effective

People’s response to placebos has been increasing by almost 7% per decade since 1981. I’m not exactly sure what the implications are for security, but they’re probably significant. For drug companies, this is huge… to the point they’ve started specifically designing studies to reduce the placebo effect, by selecting for placebo non-responders.

Rather than changing human psychology, it’s possible this is the result of study participant composition changing. (Study participants used to be mostly unpaid inpatients in the ’60s and ’70s. Now they’re mostly paid outpatients, found via subway and bus ads.)

“The response to placebo in these studies varied from 10% to more than 50%. Over time, placebo response increased by an average of 7% per decade, going from 21% in 1981 to 35% in 2000.

Interestingly, it wasn’t just placebo response that went up in this time frame. Drug response went up too, at nearly the same rate as placebo response. ”

“The pharma industry has a big problem on its hands: Placebos are getting to be way too effective. Something needs to be done. But what? What can you do about placebo response? The old saying “It is what it is” would seem to hold true in this case.

One answer: come up with low-placebo-response study designs, and patent them if possible. (And yes, it is possible. But we’re getting ahead of the story.) […]

The drug companies say these failures are happening not because their drugs are ineffective, but because placebos have recently become more effective in clinical trials. (For evidence on increasing placebo effectiveness, see yesterday’s post, where I showed a graph of placebo efficacy in antidepressant trials over a 20-year period.) […]

Some idea of the desperation felt by drug companies can be glimpsed in this slideshow (alternate link here) by Anastasia Ivanova of the Department of Biostatistics, UNC at Chapel Hill, which discusses tactics for mitigating high placebo response. The Final Solution? Something called The Sequential Parallel Comparison Design.

SPCD is a cascading (multi-phase) protocol design. In the canonical two-phase version, you start with a larger-than-usual group of placebo subjects relative to non-placebo subjects. In phase one, you run the trial as usual, but at the end, placebo non-responders are randomized into a second phase of the study (which, like the first phase, uses a placebo control arm and a study arm). SPCD differs from the usual “placebo run-in” design in that it doesn’t actually eliminate placebo responders from the overall study. Instead, it keeps their results, so that when the phase-two placebo group’s data are added in, they effectively dilute the higher phase-one placebo results. The assumption, of course, is that placebo non-responders will be non-responsive to placebo in phase two after having been identified as non-responders in phase one. In industry argot, there will be carry-over of (non)effect from placebo phase one to placebo phase two.”

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