Ethical and scientific challenges of placebo control arms in clinical trials

The ethical and scientific issues in therapeutic and diagnostic clinical research that involve placebo treatment in a control group of patients has been a source of concern for some time. The Declaration of Helsinki in its 1996 amendment tried to clarify placebo usage in biomedical research but, in the opinion of many, it has confused the situation. This paper reviews several aspects of the use of placebos in clinical trials. After a brief historical background, the need for control groups in randomized clinical trials is presented. The placebo-control design raises questions of deception, of patient information and informed consent, of patient bias and unblinding from such information, and of withholding active treatment by randomized allocation of trial medication. There are a number of control group options that can fulfil ethical and scientific needs. Examples of such acceptable placebo treatment arms are given in clinical trials of depression, epilepsy, Alzheimer's disease and other forms of dementia. Finally, a decision tree is offered and a possible rewording of the relevant clause in the Declaration of Helsinki.