Confusion over use of placebos in clinical trials

Abstract

Better guidelines needed “Medicine the science” is gradually replacing “medicine the art,” and demands for treatments to be evidence based have given the process a recent fillip.1 The key to this transition has been the controlled clinical trial, which, for drugs at least, is now an essential component for assessing interventions. But the clinical trial is more than a scientific instrument, for in addition to meeting the needs of the scientist it must also satisfy licensing authorities, marketing departments, prescribers, consumers, ethicists, lawyers, and often all of these in many countries. With such diverse interests, disagreements over the design of trials are inevitable, and one area in which conflict arises is in the use of the placebo. On page 844 of this week's journal Aspinall and Goodman, who have analysed trials of ondansetron for postoperative nausea and vomiting, argue that placebos have been used so excessively that patients have been deprived of effective treatment.2 Similar concerns were raised last year about trials of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, antidepressants, and ondansetron (when used for the treatment of nausea and vomiting induced by chemotherapy).3 These allegations need addressing. Firstly, however, understanding of what determines the use of placebos is important. Controlled clinical trials are designed to show whether a product has a pharmacological effect. Some trials seek evidence by using historical comparisons, some by comparing the product with no treatment, and others by showing a doseresponse relation for the new drug. But proof is scientifically strongest if data …