Examples Controlled clinical trials Controlled

clinical trials, especially in the form which up to now has been the gold standard, ie, the double-blind randomized controlled clinical trial (RCCT) are research studies for the proof of efficacy and safety of a new intervention. Objective influences on the outcome of a specific intervention are controlled by randomizing the allocation of research subjects to the index group and to the control group, and subjective influences byblinding the patient and – if necessary – the researcher Inhibitors,research,lifescience,medical (double-blinding). However, the more the sample of research subjects is selected according to strong inclusion and exclusion criteria, the less the generalizability of results will Inhibitors,research,lifescience,medical be. Therefore, the result of the same intervention in nonselected samples from routine practice may differ, and justifies additional trials under

naturalistic conditions. Two controversially debated ethical issues are placebocontrolled trials and the “therapeutic misconception.” Placebo-controlled trials The revision of article 29 of the Helsinki Declaration in 2000 and its “Note of Clarification” in 2002 on the use of placebo controls in cases Inhibitors,research,lifescience,medical of an existing standard treatment provoked a heated controversy between advocates of an “active control orthodoxy” as opposed to those

of a “placebo orthodoxy.” 2 The former argue that withholding a proven standard therapy is unethical and violates the ethical principle of nonmaleficence, Inhibitors,research,lifescience,medical whereas the latter defend the position that placebo controls are necessary to evidence the efficacy of a new intervention in cases, in which the efficacy of an established standard treatment is Serotonin receptor antagonist drugs supplied only by historical and clinical experience. The discussion was intensified a decade ago also by the usage of purely placebo-controlled RCCTs in patients with schizophrenia, Inhibitors,research,lifescience,medical and resulted in the operationalization Rebamipide of a set of criteria for an ethically acceptable use of placebos in controlled trials of patients for whom a standard therapy is available.3 Further pro arguments are high placebo rates in the field of indication, a high risk of side effects of the standard treatment, or its efficacy on only single symptoms.4,5 Particularly controversial was the debate about placebo controls in depression: whereas some argue for their indispensability6,7 in order to avoid ostensible evidence by equivalence with an inefficient standard treatment, others are convinced of the efficacy of antidepressant drugs, especially in severe depression.8,9 Efficacy is less evident in mild depression.