[Placebo in clinical research--a continual compromise between ethical requirements and scientific rigor]

The use of placebo in clinical trials has been the object of continuous controversy. If effective treatment is not available, then the comparison of a new treatment versus placebo is the only sound and ethical approach. If effective treatment exists and its withdrawal can cause severe or irreversible harm or severe suffering, the use of placebo is forbidden. In all other instances, the scientific community has been divided into two extreme positions: the placebo orthodoxy considers the use of placebo as the only scientifically and hence ethically valid approach; and the active-control orthodoxy denies the use of placebo and recommends the comparison between active treatments. The latter has been supported by the Declaration of Helsinki that, until the Edinburgh 2000 Version, denied the use of placebo whenever effective treatment existed. This position has been the object of recent, strong criticism by ethicists and international Institutions, to the point that in October 2001 the World Medical Association decided to review paragraph 29 of the Declaration. The new version of the Declaration admits the use of placebo, even in the presence of effective treatment, when there are scientifically sound methodological reasons or when the patients receiving placebo are not exposed to any additional risk of serious or irreversible harm. The problem now is that the sudden opening of the World Medical Association may be interpreted as an encouragement to use placebo. Thus, it is necessary to define a new area for a scientifically motivated, but not unscrupulous use of placebo.