Aiming to please

As a clinical research tool, a placebo is often referred to as nothing but a sugar pill – neutral and benign. In fact, “placebo” comes from the Latin word meaning “I shall please.” Everything about the word would seem to be guileless. Or that’s what the general thinking is anyway.

In last week’s e-Alert “Seeing Red” (7/16/03) I told you about two different studies in which red clover extract was tested in the treatment of menopausal hot flashes. In both studies, the group of women who received red clover showed about the same rates of success in controlling hot flashes. But the subjects in the placebo group in one study reported almost no effect at all, while in the other study the placebo subjects had almost the same results as the red clover group.

How could the results of these two placebo groups be so different? One strong possibility: The placebos may have been very different. Because contrary to common thinking, clinical research trials – especially pharmaceutical trials – bring a whole new meaning to the old Latin idea of “I shall please.”

The importance of being inert

There was a time when doctors would prescribe phony medication – sugar pills – to their patients who they regarded as hypochondriacs. They called the pills “placebo” and when the patients reported positive results the idea of the placebo effect was born.

These days, placebo pills are used in clinical trials to measure the true effect of a drug or supplement. They are thought to be made of inert substances designed to have no effect. But consider this: there’s no such thing really as an inert substance. For instance, placebo pills are still called sugar pills. Is sugar inert? Far from it, of course. If you take a sugar pill, your body will have a reaction, especially if you happen to have an insulin disorder. But if you’re given that same pill as part of a drug research trial, your reaction becomes a factor in the research.

That may seem like nothing (what real difference could a little boost of sugar make?) but sugar and other supposedly inactive ingredients are not the issue. Not in the least.

A little secret

When a pharmaceutical company tests its products, where do you suppose they get placebo pills? Do they place an order with a placebo pill manufacturer? Or does Nestle’s candy company run a little side business to supply researchers with sugar pills?

The fact is, drug companies make their own placebo pills for research purposes, and for each individual study they create a unique placebo formula – sometimes purposely including ingredients that match ingredients in the drugs being tested. But at no time do the contents of the placebos have to be revealed.

Does that sound “inert” or “inactive” to you? Suddenly the idea of a “sugar pill” doesn’t seem so innocent anymore.

Before conducting human trials for drugs, pharmaceutical companies are often fully aware of many of the side effects of the products they’re testing. So, for instance, if a drug is known to cause dizziness and nausea, the drug company running the test wants the placebo to have the same side effects. And they have an explanation for this. They say the placebo should mimic the drug being tested so that the control group of the experiment will have side effects similar to the placebo group. Without that, they claim, the results of a blind study would be compromised.

There are plenty of gray areas to debate in that logic, but for the moment let’s focus on the idea of what they call an “active placebo,” designed to mimic the side effects of a tested drug. And with that in mind let’s look at an advertising campaign for the allergy medication called Claritin. In the Claritin TV spots, when it comes to the moment to list the side effects, the voice-over says, “The most common side effects with Claritin, including headache, drowsiness, fatigue and dry mouth, occurred about as often as they did with a sugar pill.”

A sugar pill? Really? Just what kind of “sugar pill” were the researchers using that caused headache, drowsiness, fatigue and dry mouth? Sounds to me like a sugar pill with a little something added. But they want us to believe that this medication will produce side effects no more serious than what you’d get with a TicTac.

The whistle blower

Dr. Beatrice Golomb, MD, PhD, is an assistant professor of medicine at the University of California, San Diego, and has been actively fighting the research establishment’s claim that placebos are inactive substances. Dr. Golomb wants scientists to provide a list of placebo ingredients so trial results can be properly evaluated.

To level the playing field, Dr. Golomb suggests that drug companies start divulging all placebo ingredients. She also recommends that a standardized set of placebos be developed that would have known and predictable side effects. This would go a long way toward eliminating the pharmaceutical industry’s cynical manipulation of test data.

As you might suspect, the drug companies are not very receptive to Dr. Golomb’s idea of letting go of this aspect of product testing that they have full control over.

Meanwhile, what about physicians and researchers who work independently from the pharmaceutical giants – do they know the truth about placebos supplied by drug companies? Right now it’s hard to tell just how widespread this knowledge is. According to the National Center for Complementary and Alternative Medicine at the National Institutes of Health (NIH), the placebo effect is defined as “desirable physiological or psychological effects attributable to the use of inert medications.” From that statement it would appear that NIH officials either believe that placebos are genuinely inactive, or they’re not admitting that they know better.

Or maybe they’re just feeling drowsy, dizzy, irritable and nauseous from a sugar pill someone gave them.

To Your Good Health,

Jenny Thompson
Health Sciences Institute