Placebo-controlled trials of new drugs: ethical considerations.

Abstract

Much controversy exists regarding the ethics of placebo-controlled trials in which an experimental therapy will compete with an already established treatment (or treatments). In such cases, argue critics, patients in the control arm of the study should receive an accepted therapy rather than a placebo. By using an active and effective drug, the control patients would not be placed at risk for deterioration of their disease, and the study would generate more meaningful results for physicians. The key question, it is said, is not whether a new therapy is better than nothing but whether it is better than the current standard of care (1,2). In response, say proponents of placebo-controlled trials, critical information cannot always be obtained by giving control patients an existing therapy. For some effective therapies, the drug may perform no better than placebo in a particular trial even though other trials demonstrate the drug’s superiority to placebo. If an experimental agent confers the same benefit as such an existing therapy in a comparative trial, we cannot be certain that the new agent is any better than placebo. We might have one of the trials in which the existing therapy (and therefore the new agent) does no better than placebo, perhaps because of inadequate sample size, perhaps because the outcome measure can vary widely from one patient group to another (3–5). In addition, some new therapies are useful even if they are less effective than existing therapies. Some patients might choose a less effective drug if substantial cost savings or a reduction in side effects would be realized (6). Without a placebo control, however, one cannot always tell whether a new drug that is not as effective as existing therapy is still sufficiently more effective than placebo to justify its use. Finally, not …