Analysis of clinical trials reveals that placebo content is rarely described

A new paper entitled ‘What’s in Placebos: Who Knows? Analysis of Randomized, Controlled Trials’ was published in the Annals of Internal Medicine on 25th October 2010.

On reflection, it is surprising that a study such as this has not been carried out before now. With the concept of placebos so high on the public agenda, courtesy of the publicity given the revered randomised, placebo-controlled trial (RCT) by the mainstream media, it seems blindingly obvious that the placebos should also come under scrutiny.  At the very least the substances used as placebos should both be disclosed and established not to affect the outcome of the trial.

In fact, what these researchers have uncovered gives grave cause for concern, as trials that do report details of their placebo formulations are very unusual exceptions. The rule appears to be to say “You can trust us, we’re using inert substances that will have no bearing on the trial results”, while not disclosing any information on what those substances might be! While it may very well be true that the companies and organisations running clinical trials are whiter-than-white in terms of the substances given to patients as placebo, the potential for mistakes, invalid results and plain old medical fraud are huge.

Just think: it would be so easy for unscrupulous researchers to pollute their anonymous placebo with a substance that made those patients a little bit sicker – even if only on one or two clinical indicators – and thereby skew the results in favour of the trial drug. Placebos are often known as “sugar pills”, but what would be the effect of a real sugar pill in an RCT for a type II diabetes drug? It would be a black day indeed for the pharmaceutical industry if it turned out that decades of clinical trials were declared invalid, due to a lack of definitive evidence that their placebos were safe and inert.

These researchers have taken an important first step toward full disclosure of the true state of the science behind RCTs. We await further developments with interest.

Access the abstract and full paper.

Short summary of the abstract:

Background: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting.

Purpose: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials.

Data Synthesis: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002).

Limitation: Journals with high impact factors may not be representative.

Conclusion: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.

Golomb BA, Erickson LC, Koperski S, Sack D, Enkin M, Howick J. What’s in Placebos: Who Knows? Analysis of Randomized, Controlled Trials. Annals of Internal Medicine 2010; 153: 532–535.

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