Pharmaceutical companies have discovered an unexpected nemesis in their quest to bring new drugs to market: the placebo.
As Steve Silberman reports in a recent article in Wired magazine, the percentage of new pharmaceutical products being scrapped due to poor performances in clinical trials has been climbing steadily over the past decade.
Today, “[h]alf of all drugs that fail in late-stage trials drop out of the pipeline due to their inability to beat sugar pills,” he says. (For FDA approval, a new drug must beat a placebo in at least two trials.)
Furthermore — and this has drug companies equally worried — even some of its older products, like Prozac, are not faring well against the placebo in follow-up trials. Writes Silberman:
In many cases, these are the compounds that, in the late ‘90s, made Big Pharma more profitable than Big Oil. But if these same drugs were vetted now, the FDA might not approve some of them. … It’s not that the old meds are getting weaker, drug developers say. It’s as if the placebo effect is somehow getting stronger.
The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today’s economy, the fate of a long-established company can hang on the outcome of a handful of tests.
Silberman reports that Big Pharma, under the auspices of the National Institutes of Health, has launched a sort of hush-hush program (people would talk about it only anonymously) to figure out exactly why the placebo effect has been gaining strength.
I found a couple of the proposed explanations for this conundrum by the article’s experts particularly intriguing:
• Direct-to-consumer advertising of antidepressants, statins and other “blockbuster drugs” in the United States has been so successful that it’s difficult for Big Pharma to find potential volunteers here who aren’t already taking some kind of medication.
So drug companies are going overseas (Africa, India, China, and the former Soviet Union) to conduct their trials. But there they’re finding that “cultural dynamics can boost the placebo response in other ways,” says Silberman. “Doctors in these countries are paid to fill up trial rosters quickly, which may motivate them to recruit patients with milder forms of illness that yield more readily to placebo treatment.”
• When it comes to psychiatric drugs, one of Big Pharma’s problems with beating placebo may lie in its expansive definition of mental illnesses, including depression.
“Existing tests also may not be appropriate for diagnosing disorders like social anxiety and premenstrual dysphoria — the very types of chronic, fuzzily defined conditions that the drug industry started targeting in the ‘90s, when the placebo problem began escalating,” writes Silberman. “The neurological foundation of these illnesses is still being debated, making it even harder for drug companies to come up with effective treatments.”
After reading the article, I found myself wondering whether what’s running amok is not the placebo effect, but disease mongering (the invention of nonexistent medical conditions or the exaggeration of ordinary ailments in order to sell drugs or procedures).
Now, if only that could be cured with a pill.
FYI:
To learn more about the latest research on the placebo effect, I recommend Maj-Britt Niemi’s article in last February’s Scientific American Mind.
It’s an interesting subject, isn’t it. But the context is interesting too. Newer generation antidepressants have been unable to beat placebos beyond a clinically significant margin for the entirety of their use, if we are to place our trust in comprehensive pooling studies (meta-analyses).
One researcher who looked at the entire FDA database (Kirsch) found the difference between SSRI’s and sugar pills — according to the industry’s best efforts to prove their pills worked — amounted to an average of 2 points on the Hamilton Depression Inventory. That’s about the amount of benefit you’d receive from a good night’s sleep, in his words. A more recent study (by Kirsch and Deacon) found that this held right up to the very severest cases.
Many of these studies had already threw out placebo responders in the early weeks after enrolling subjects, already stacking the deck in the drug’s favor, as it were. So one could ask if the placebo effect is getting stronger — which seems possible, as you say, given all the marketing and broadening of their use. But another good question for Wired to have asked might have been how could the drugs perform more poorly than they already have?
This hardly seems mysterious.
The placebo effect happens when the patient is sufficiently convinced that a treatment will work. The actual mechanism, though officially unknown, may very well be that the body’s own recuperative and/or pain management abilities are invoked by the faux treatment. But doubt is the enemy. If a patient is not convinced that the “drug” can help, the placebo effect disappears.
With direct-to-consumer drug advertising continuing to expand essentially unchecked, the industry has spent all kinds of money trying to convince the public that there is a drug for every possible malady, and that every single drug is the last word in treatment for its target disease (existent or not). An increase in the public’s overall belief in the potential effectiveness of drugs would seem a natural and direct result.
Putting these two things together you can see that the public is now generally more predisposed to believe that some new treatment will actually work. The advertising has accomplished this.
Thus, the entire pool of possible test subjects (at least in the US) is tainted by these increased beliefs. (I’m not a scientist, but something like this really should be in the list of possible explanations.)
If overseas trials are affected for the reasons mentioned in this article (tainted and hastily-selected volunteers), then they are useless for any data to begin with, including placebo effect data.
Now the question might be: Does the drug industry know how to analyze itself?
What irony if it ever could be established that the widespread advertising had led, even indirectly, to either a reduction in drug effectiveness, or an increase in a placebo-related alternative.
Read the entire article before posting criticisms, please.
It is clear that the writer of this article never read the full article or she would not have written this:
After reading the article, I found myself wondering whether what’s running amok is not the placebo effect, but disease mongering (the invention of nonexistent medical conditions or the exaggeration of ordinary ailments in order to sell drugs or procedures).
Now, if only that could be cured with a pill.
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As the article states the origin of the placebo effect was a nurse who, having run out of morphine, injected sugar water into a wounded soldier. His leg was blown off!!
This is a breakthrough story in Wired. The placebo effect does not mean that it only appears in bogus diseases or that the benefit is “imagined.” The brain actually believes it and the brain creates chemicals as if the drug were real.
Please, put your thinking caps on and re-read this article.
The main point of the article is the mind/body connection with respect to health and healing. If you believe that it will work, it often does. But the beauty of the Wired article is that it digs much deeper into the question of just what is a placebo.
For me, the main take away was that I have more control over my chronic pain, due to nerve damage from failed surgeries. That I started doing biofeedback and meditation my pain levels are lower.
When meditators are monitored we see their blood pressure being reduced, heart rate slowing down, and a whole host of bodily functions being controlled by the individual. This is not supposed to be possible according to current neurological dogma, as taught in the best medical schools in the country and the world.
If you are still skeptical, search “neuroplasticity” and you will see that the number of brain cells (neurons) is not fixed at birth and depleting throughout life. This is the exact opposite of what we were taught our entire lives until around 8-9 years ago when neuroplasticity was discovered and scientifically verified.
This article in Wired is *very* significant and a great read.