Kenter, M. J. & Cohen, A. F. Establishing risk of human experimentation with drugs: lessons from TGN1412. Lancet 368, 1387-1391

Central Committee on Research Involving Human Subjects, The Hague, Netherlands.
The Lancet (Impact Factor: 45.22). 11/2006; 368(9544):1387-91. DOI: 10.1016/S0140-6736(06)69562-7
Source: PubMed


Particular care is necessary when a new drug is given to healthy volunteers without previous human testing. General principles for such research have been laid down in guidelines as early as 1983, and these were the basis for many current regulations. 2 Most drugs at that time were small molecules with fairly well characterised, classic, pharmacological mechanisms. Proposed primary objectives for studies in healthy people were therefore to show pharmacological action in man and the dose (or concentration) response curve. This approach was judged safe and was lent support by fi ndings of available surveys. 3,4

  • Source
    • "between humans and cynomolgus monkeys, TGN1412 would bind poorly or not at all in the monkey, thereby making it resistant to its stimulatory effects (Kenter and Cohen, 2006 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The failure of toxicity studies in non-human primates to predict the cytokine release syndrome during a first-in-man study of the CD28-specific monoclonal antibody TGN1412 has remained unexplained so far. In this issue of the BJP, work from the NIBSC first identifies the effector memory subset of human T-lymphocytes as the most likely source of the pro-inflammatory cytokines released during the study, and goes on to show that in cynomolgus monkeys, this subset lacks CD28, the target molecule of TGN1412. We discuss the implications for the TGN1412 catastrophe and for preclinical evaluation of biologicals in animal models in general.
    Full-text · Article · Oct 2010 · British Journal of Pharmacology
  • Source
    • "However, we also demonstrate that an important form of industry protection is actually compatible with the duty to disclose clinical trial results. A key concern in this paper is to balance, appropriately, the competing moral claims presented 3 The more recent TGN1412 trial at Northwick Park is another, more complex and controversial example of involving this kind of non-disclosure (Kenter and Cohen 2006, Schneider et al. 2006). by the risk of harm to trial participants and the benefits delivered by a productive pharmaceutical industry. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Participants in some clinical trials are at risk of being harmed and sometimes are seriously harmed as a result of not being provided with available, relevant risk information. We argue that this situation is unacceptable and that there is a moral duty to disclose all adverse clinical trial results to participants in clinical trials. This duty is grounded in the human right not to be placed at risk of harm without informed consent. We consider objections to disclosure grounded in considerations of commercial interest, and we argue that these concerns are insufficient to override the moral duty to disclose adverse clinical trial results. However, we also develop a proposal that enables commercial interests to be protected, while promoting the duty to disclose adverse clinical trial results.
    Full-text · Article · Aug 2009 · The American Journal of Bioethics
  • Source

    Preview · Article ·
Show more