Placebo controls, ethical considerations

In some situations double-blind placebo-controlled trials are not acceptable from an ethical standpoint examples are studies on patients in life-threatening conditions such as severe withdrawal symptoms (e.g. delirium tremens) or diseases with a high risk of suicide. To keep double-blind conditions in longterm treatment may also be difficult or even impossible, e.g. if one of the drugs used needs special safety monitoring or if the side-effect profile requires special treatment considerations. 

In general, according to EU law, applicants are expected to carry out controlled clinical trials, randomized and as appropriate against a placebo and an established medicinal product (an active comparator) of proved therapeutic value. However, applicants may justify use of other trial design. The treatment of the control groups will vary from case to case and also will depend on ethical consideration and therapeutic area. In some cases it may be more justified to compare the efficacy of a new medicinal product with that of an established medicinal product of proved therapeutic value rather than with a placebo. 

Although the use of a placebo control is generally preferred, this study design is not always possible because of ethical considerations. Fatal or potentially fatal illness, such as malignancy, severe depression, or infections must not go untreated in randomly selected patients simply to satisfy the ideal study design. However, if no placebo is used and the new therapy can be compared only with another therapy, the analysis of the results should at least address the... 

Control group treatment established medical product or treatment,placebo less likely, due to ethical considerations. 

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