On March 26, 2007, the European Medicines Agency in London released for comment its “first-in-man” clinical trials guidelines for potential high-risk medicinal products. The guidelines follow extensive discussion of the serious adverse events that occurred to six subjects in the TGN1412 trials last year. The focus is on “products where the mode of action, the nature of the target in the human body or the limited relevance of animal models for the prediction of pharmacological or toxicological events in humans raises concerns that serious adverse reactions may occur.” It also gives advice on calculation of the initial dose to be used in humans, intervals between doses within a cohort, subsequent dose escalation, and the management of risk. The guidelines appear to be the mirror image of the TGN1412 protocol. Comments will be accepted until May 23.
To my knowledge, there has been no comparable public discussion in the U.S.