Abstract: As a general rule, research subjects in the control group of a biomedical research involving human subjects should receive an established effective intervention.In some circumstances, however, it may be ethically acceptable to use an alternative comparator, such as placebo, “ no treatment” or other effective alternative. This article discusses these special circumstances in detail, and puts forward means of minimizing harm to placebo- control subjects.

Key words: medical ethics, clinical trial, Council for International Organizations of Medical Sciences, guideline, ethical, thedesign of study