TY - JOUR
KW - animal experimentation
KW - Animals
KW - Drug Evaluation, Preclinical
KW - Drug-Related Side Effects and Adverse Reactions
KW - Humans
KW - Primates
AU - Jarrod Bailey
AU - Michelle Thew
AU - Michael Balls
AB - 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 non-human 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.
BT - Alternatives to laboratory animals: ATLA
DA - 2015-12
DO - 10.1177/026119291504300607
IS - 6
LA - eng
N2 - 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 non-human 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.
PY - 2015
SP - 393
EP - 403
ST - Predicting human drug toxicity and safety via animal tests
T2 - Alternatives to laboratory animals: ATLA
TI - Predicting human drug toxicity and safety via animal tests: can any one species predict drug toxicity in any other, and do monkeys help?
VL - 43
SN - 0261-1929
ER -