title: Animal extrapolation in preclinical studies: An analysis of the tragic case of TGN1412.
abstract: According to the received view, the transportation view, animal extrapolation consists in inductive prediction of the outcome of a mechanism in a target, based on an analogical mechanism in a model. Through an analysis of the failure of preclinical studies of TGN1412, an innovative drug, to predict the tragic consequences of its first-in-man trial in 2006, the received view is challenged by a proposed view of animal extrapolation, the chimera view. According to this view, animal extrapolation is based on a hypothesis about how human organisms work, supported by the amalgamation of results drawn from various experimental organisms, and only predicting the 'predictive grid', that is, a global framework of the effects to be expected.
authors.affiliation: INSERM U930, France; Université de Tours - Faculté de Médecine - Département de SHS, 10 Bd Tonnellé 37032 Tours Cedex, France. Electronic address: lemoine@univ-tours.fr.
authors.forename: Maël
authors.initials: M
authors.lastname: Lemoine
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000276:immunology*; D004353:Drug Evaluation, Preclinical / Q000009:adverse effects; D006801:Humans
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C509303:TGN-1412
keywords: Animal extrapolation; Experimental organism; Mechanistic thinking; Preclinical studies; Prediction