[Ethical questions in clinical research with the mentally ill]

The review deals with present problems of protecting mentally ill patients who are incompetent to give informed consent to participating in clinical research, and of assessment of the capacity to consent. 1. Clinical trials of drugs on efficacy and safety in incompetent patients are ethically justified and legally admissible if the investigational drug can be expected to exert a direct potential individual benefit and if such trials will be performed under defined criteria to protect these vulnerable patients. In Germany it is questionable how far these prescriptions of the German Drug Law (AMG) are transferable to other than drug research. 2. Research with no direct potential individual benefit or only a group-specific benefit in incompetent patients is controversially discussed. However, it may be ethically justified as an exception, and is in Germany legally admissible only in minors, but not in adults. 3. However, internationally there exists a wide range of legal regulations, terms, interpretations, and practices of research with vulnerable persons. In the past years a shift seems to have developed from normatively oriented discussions to more empirically based investigations. Especially vague but clinically relevant terms in protection declarations or guidelines have been better specified, put in concrete form by anchor examples, and empirically studied. 4. In general the criteria of protecting the dignity and, even if impaired, the autonomy of incompetent patients as subjects for research appear to guarantee a high standard of protection. However, the application of these criteria must be improved by practicable procedures. This is valid particularly for the assessment of the basic criterion whether a patient is capable of consenting or not. 5. Open Questions are formulated as need of research.