title: Animal models of efficacy to accelerate drug discovery in malaria.
abstract: The emergence of resistance to artemisinins and the renewed efforts to eradicate malaria demand the urgent development of new drugs. In this endeavour, the evaluation of efficacy in animal models is often a go/no go decision assay in drug discovery. This important role relies on the capability of animal models to assess the disposition, toxicology and efficacy of drugs in a single test. Although the relative merits of each efficacy model of malaria as human surrogate have been extensively discussed, there are no critical analyses on the use of such models in current drug discovery. In this article, we intend to analyse how efficacy models are used to discover new antimalarial drugs. Our analysis indicates that testing drug efficacy is often the last assay in each discovery stage and the experimental designs utilized are not optimized to expedite decision-making and inform clinical development. In light of this analysis, we propose new ways to accelerate drug discovery using efficacy models.
authors.affiliation: GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Jiménez-Díaz
authors.affiliation: GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Viera
authors.affiliation: GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Fernández-Alvaro
authors.affiliation: GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Angulo-Barturen
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods; D000882:Haplorhini / Q000469:parasitology*; D006801:Humans; D008018:Life Cycle Stages / Q000187:drug effects; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008822:Mice, Transgenic / Q000469:parasitology*; D010961:Plasmodium / Q000187:drug effects / Q000254:growth & development; D013997:Time Factors
chemical_list: D000962:Antimalarials