02145nas a2200301   4500000000100000000000100001008004100002260001200043653002700055653001200082653003300094653005200127653001100179653000900190653001900199653001200218653000900230653001500239100001800254700001800272700001800290245009100308856006300399300001200462490000700474520134800481022001401829       2014                            d  c2014-0610aanimal experimentation10aAnimals10aDrug Evaluation, Preclinical10aDrug-Related Side Effects and Adverse Reactions10aHumans10aMice10aModels, Animal10aRabbits10aRats10aToxicology1 aJarrod Bailey1 aMichelle Thew1 aMichael Balls00aAn analysis of the use of animal models in predicting human toxicology and drug safety  uhttps://alzres.biomedcentral.com/articles/10.1186/alzrt269  a181-1990 v423 aAnimal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1-4 biomedical observations. This was done for three preclinical species (rat, mouse and rabbit), to augment our previously-published analysis of canine data. In common with our dog analysis, the resulting LRs show: a) that the absence of toxicity in the animal provides little or virtually no evidential weight that adverse drug reactions (ADRs) will also be absent in humans; and b) that, while the presence of toxicity in these species can add considerable evidential weight for human risk, the LRs are extremely inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Therefore, our results for these additional preclinical species have important implications for their use in predicting human toxicity, and suggest that alternative methods are urgently required.  a0261-1929