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 Sources: 4 English-language general and internal medicine journals with high impact factors.
Study Selection: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009.
Data Extraction: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus.
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.
In many trials of new drugs in development such as cardiovascular, dermatology, neuroscience etc, the test agent is typically compared to a placebo with a similar formulation such as a pill, topical cream etc, but as the journal points out, rarely is the composition defined in detail.
This is not surprising, as the authors of the paper reported that they found that only a paltry 8.2% of the 86 studies they looked at actually stated clearly what the contents of the placebo were.
Does it matter?
Well, you might think it's just a 'sugar pill', but as this article in the LA Times noted, some placebos in cardiovascular trials might consist of olive oil or other polyunsaturated oils, thereby potentially reducing cholesterol and heart disease. Certainly something to think about, as they may have unexpected effects.
Although most cancer clinical trials are typically comparing a new treatment to the standard of care, often placebo is used in the comparator combination. A recent example is the abiraterone trial reported last week at ESMO in men with advanced, castration resistant prostate cancer after prior docetaxel therapy. The study compared abiraterone (a pill) with prednisone (a steroid) to placebo (pill) plus prednisone. Based on the information provided in clinicaltrials.gov, it isn't clear what the placebo actually was.
I liked the quote from the authors in the LA Times article above:
"Perfect placebo is not the aim, rather, we seek to ensure that its composition is disclosed."
Given the placebo could have unexpected effects or at least have an impact, perhaps we should start disclosing what's actually in them.