First-in-Man (FIM) clinical trials post-TeGenero: a review of the impact of the TeGenero trial on the design, conduct, and ethics of FIM trials.

A recent first time in man (FIM) trial of an "immuno modulator" compound (TGN1412) resulted in unprecedented toxicity. Since this occurred in 2006 a widely publicized scientific debate, as well as a controversy in the lay community has examined the principle of design and content of the study as well as the concept of FIM studies. This paper reviews the controversy, analyzes the problems of the TGN1412 trial and FIM trials in general and the reaction of the lay and scientific communities. Difficulties in these high risk trials is highlighted and possible design and execution procedural improvements are recommended. Consideration is given to the ethical debate regarding participation of normal, healthy research volunteers in FIM studies. The role of monetary incentive(s) is discussed as well as the opposition of many participants in this debate on financial compensation of volunteers for the assumption of risk and the need to adopt a no-fault scheme that fairly compensates injured trial participants.FIM studies are critical for the development of new therapeutic agents. Improving trial design and execution and fairly compensating volunteers will facilitate these studies, enhance equity and thus provide an ethical basis for continuing FIM studies that may pose a serious risk to participants, a risk that society needs taken for the development of needed therapeutic agents.