drug safety

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Predicting Human Drug Toxicity and Safety via Animal Tests: Can Any One Species Predict Drug Toxicity in Any Other, and Do Monkeys Help?

Jarrod Bailey, Michelle Thew and Michael Balls

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for different classes of drugs. Here, we present further data from analyses of other species pairs, including nonhuman primates (NHPs), which support our previous conclusions, and also show in particular that test results inferring an absence of toxicity in one species provide no evidential weight with regard to toxicity in any other species, even when data from NHPs and humans are compared. Our results for species including humans, NHPs, dogs, mice, rabbits, and rats, have major implications for the value of animal tests in predicting human toxicity, and demand that human-focused alternative methods are adopted in their place as a matter of urgency.
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Toxicogenomics in Drug Discovery and Development — Making an Impact

Quin Wills and Cathrine Mitchell

As a branch of pharmacogenomics aimed at predicting drug safety concerns, toxicogenomics drew much excitement with the emergence of technologies such as gene expression microarrays. A few years down the line, the evidence is scant that current approaches to toxicogenomics are really making an impact in areas such as preclinical toxicology. It has been argued that there needs to be a re-focus of application toward high-throughput approaches which combine the best of tissue and genomic modelling. This commentary gives a brief introduction to in vitro toxicogenomics, drawn from the perspectives of the specialist toxicogenomics company, SimuGen.
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The Rational Use of Animals in Drug Development: Contribution of the Innovative Medicines Initiative

Magda Gunn, Elisabetta Vaudano and Michel Goldman

Animal models are still widely used to assess the efficacy or safety of new pharmaceutical products. Since their limitations in predicting actions of drugs in humans are becoming more and more apparent, there is an urgent need to revisit the use of animals in pharmaceutical research. Herein, we review how the Innovative Medicines Initiative (IMI), the largest public–private partnership in the life sciences, is reducing, refining and replacing the use of animals in the context of its global mission, namely, to boost research and the development of new medicines across the European Union.
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