Bioethics Clinical trials Complementary and alternative medicine Medicine Surgery

Some placebos are more equal than others

ResearchBlogging.orgPerusing the news early this morning, I noticed an article on ABC News about placebos. One thing I found interesting about it was that it was a story about a research letter to JAMA, not a full study. Heck, there isn’t even an abstract.

Even so, the study was rather interesting and described thusly:

The more expensive your pain medications are, the better the relief you get from taking them — even if they’re fake.

That’s according to a study published this week in the Journal of the American Medical Association, which suggests that sugar pills labeled as expensive drugs relieve pain better than sugar pills labeled as discounted drugs.

Of course, this is entirely consistent with what is known about the placebo effect, namely that more invasive and elaborate procedures or treatments tend to have a seemingly greater effect on the relief of subjective symptoms. Indeed, this is very likely a major reason why homeopathy appears to work for so many people, even though most homeopathic remedies have been diluted to nothing but water. It’s a reason why surgical procedures themselves can produce a powerful placebo effect, even when they do nothing.

So what did this little study show?

In the study, 82 volunteers were subjected to a series of electric shocks — a standard research protocol for measuring pain thresholds. They were then given a placebo pill alongside a fake drug company brochure for the fictitious drug “Veladone-Rx,” — ostensibly a new fast-acting painkiller made in China.

The only catch was that half of the test subjects received brochures showing that the drug had been marked down from the original price of $2.50 a pill to 10 cents a pill. These modified brochures also included circled fine print which suggested that the pills were manufactured in China.

After participants went through the shocks again, 85 percent in the full-price group reported pain relief from their sugar pill, while only 61 percent in the discount group reported pain relief.

This describes the brief report pretty accurately. The p-value for the above finding wasn’t the kind that would knock me out (0.03), but it was statistically significant. The authors also divided up the results according to all shocks and the highest intensity shocks only, with results as follows:


What’s also remarkable is that not only did more patients receiving the more “expensive” placebo report a reduction in pain but more patients receiving the “less expensive” placebo reported an increase in pain than those receiving the “more expensive” placebo (43.9% versus 19.5%). The results were even more striking in that increased pain relief was observed for the “expensive” placebo at all voltages used. The authors conclude:

These results are consistent with described phenomena of commercial variables affecting quality expectations1 and expectations influencing therapeutic efficacy.4 Placebo responses to commercial features have many potential clinical implications. For example, they may help explain the popularity of high-cost medical therapies (eg, cyclooxygenase 2 inhibitors) over inexpensive, widely available alternatives (eg, over-the-counter nonsteroidal anti-inflammatory drugs) and why patients switching from branded medications may report that their generic equivalents are less effective. Studies of real-world effectiveness may be more generalizable if they reflect how medications are sold in addition to how they are formulated. Furthermore, clinicians may be able to harness quality cues in beneficial ways,6 for example, by de-emphasizing potentially deleterious commercial factors (eg, low-priced, generic).

This study is, of course, rather small, but, given its consistency with much of what is known about the placebo effect, I tend to think it’s likely to be correct. Obviously, replication and extension are required. I’m not sure I agree with the authors on how this effect can be harnessed, though:

For Hadler, the study might convince doctors to develop their own positive marketing for a treatment.

In his own studies, Hadler has found that the way a physician describes a drug can change how much a patient will follow through with a treatment regimen.

“Compliance goes down when you go through all the side effects listed for the drug,” said Hadler. “But if you say, ‘This is the best thing ever, side effects are rare,’ people will respond positively.”

The problem with this approach is that it can easily flirt with being unethical and with being dishonest to patients. If there are known complications, it’s also a lovely way to leave oneself open to a malpractice suit for failure to disclose risks of treatment. On the other hand, changes in packaging to resemble brand-name drugs and other methods of making generics look less “generic” may well be helpful.

This study also suggests to me why some CAM therapies works so well. Not only do patients tend to invest a lot of effort and time into them (think acupuncture, for example, which frequently requires multiple sessions a week lasting 30 minutes or more), but these therapies can be fairly expensive. It is as though CAM practitioners instinctively understand how best to maximize the placebo effect.


Waber, R.L., Shiv, B., Ariely, D. (2008). Commercial Features of Placebo
and Therapeutic Efficacy. Journal of the American Medical Association, 299(9), 1016-1017. (Link)

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

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