ABSTRACT
Clinical trials, regardless of how well controlled and well designed, always face unavoidable potential risks and unexpected events. Perhaps the most challenging event is the unexpected death of a subject-the ultimate adverse effect (1). In spite of such events, investigational drug trials must be performed, for no alternative way exists to test new drugs safely and effectively before they are brought to the attention of the medical community. As stated in 1865 by Claude Bernard (2), a nineteenth-century physiologist:
The principle of medical and surgical morality, therefore, consists in never performing on man an experiment which might be harmful to him to any extent, even though the results might be highly advantageous to science, i.e., to the health of others…. So, among the experiments that may be tried on man, those that can only harm are forbidden, those that are innocent are permissible, and those that may do good are obligatory.
