The Real Deal on Placebos

A guest article by Nicholas Pang, self professed medical journalist

A placebo, courtesy of the kind folks at Wikipedia, from the Latin for "I will please", is a medical treatment (operation, therapy, chemical solution, pill, etc.), which is administered as if it were a therapy, but which has no therapeutic value other than the placebo effect.

One may question, how do we get people to literally put their lives on the line for this? Answer: Only people who want so, do so. Current regulations require that the researcher, as well as the test subject, will probably not know if they are receiving an active treatment or placebo. The objective of the study and its design should be clearly explained, especially the inclusion/exclusion criteria, masking procedures, and the use of medication washout, placebo, medication discontinuation and specific interventions.

Arguments For Ethical Use of Placebos

The strongest argument against placebos is such: Their use is unethical when there is a proven effective drug that can combat a disease. The new drug should be measured COMPARED to an existing drug. This is termed an equivalence or a noninferiority trial. The logical reasoning stands as thus: The drug administered to the patient will assist the patient either way; either to a larger (new treatment) or a smaller (existing treatment) magnitude.

Such proponents frequently cite Paragraph 29 of the Declaration of Helsinki which states: “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods”

Sadly, the drugs unleashed upon the world as a result of equivalence tests may actually be born of a less stringent quality control process.

Equivalence therapy - commonly deemed "proven effective therapy" - often fails to show superiority to placebo. This is not because these drugs are in fact ineffective, but because the trials in question lack assay sensitivity. Assay sensitivity is defined as the ability of a trial to distinguish an effective from an ineffective therapy.

SENSATIONAL PROOF: FDA review documents on 51 clinical trials on nine antidepressants approved between 1985 and 2000 were obtained and indicated that out of 92 active treatment arms (all involving doses that were eventually approved), 47 (51%) failed to demonstrate statistical superiority to a placebo.

Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research. To approve ineffective drugs based on flawed science and to let them loose on an unsuspecting public would be more unethical.

This Debate is Not Just about Efficacy

...it is also about harm. Not using a placebo group, it may be impossible to interpret a drug's potential for harm. The famous Vioxx study (United States) showed a five-fold difference in the incidence of myocardial infarction in the rofecoxib (Vioxx) group compared with the naproxen group the US Nonsteroidal anti-inflammatory drugs such as naproxen, however, inhibit platelet function and therefore might have a myocardial protective effect. Thus without the use of a placebo it was impossible to tell whether the changes were attributed to naproxen having a protective effect or rofecoxib having a destructive effect.

In the meantime, rofecoxib was distributed liberally to the public, and four years later, the drug was withdrawn due to an alleged "increased cardiovascular risk". The decision was based on - surprise, surprise - an unpublished Adenomatous Polyp Prevention on Vioxx (APPROVe) study, a placebo-controlled three-year trial of rofecoxib.

In his November 2004 testimony before the United States Senate, David Graham of the FDA provided an estimate of the rate of excess cases of Vioxx-related myocardial infarction and sudden cardiac death. He testified that it was as if, for the five years that Vioxx was on the United States market, “2 to 4 jumbo jetliners were dropping from the sky every week”. Of those cases, he added, 30% to 40% probably died.

If those who believe that “proven therapy” trials are ethically preferable to placebo-controlled trials had had their way, the APPROVe study would have been blocked, and Vioxx would still be on the market today, and we would be left with a heightened body count. It seems ironic that such a stance could be taken in the name of ethics.