Animal experiments scrutinised: systematic reviews demonstrate poor human clinical and toxicological utility.
The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive "Scopus" biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. Of 20 reviews examining clinical utility, authors concluded that the animal models were substantially consistent with or useful in advancing clinical outcomes in only two cases, and the conclusion in one case was contentious. Included were reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments - the species most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of experimental outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments evident in at least 11 reviews. No reviews existed in which a majority of animal experiments were of good quality. While the latter problems might be minimised with concerted effort, given their widespread nature, the interspecies limitations are likely to be technically and theoretically impossible to overcome. Yet, unlike non-animal models, animal models are not normally subjected to formal scientific validation. Instead of simply assuming they are predictive of human outcomes, the consistent application of formal validation studies to all test models is clearly warranted, regardless of their animal, non-animal, historical, contemporary or possible future status. Expected benefits would include greater selection of models truly predictive of human outcomes, increased safety of people exposed to chemicals that have passed toxicity tests, increased efficiency during the development of human pharmaceuticals, and decreased wastage of animal, personnel and financial resources. The poor human clinical and toxicological utility of most animal models for which data exists, in conjunction with their generally substantial animal welfare and economic costs, justify a ban on animal models lacking scientific data clearly establishing their human predictivity or utility.
Knight
Andrew
A
Animal Consultants International, London, UK.
D032761:Animal Experimentation; D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods*; D004195:Disease Models, Animal; D019317:Evidence-Based Medicine / Q000379:methods / Q000592:standards; D006801:Humans; D023421:Models, Animal; D015203:Reproducibility of Results; D014116:Toxicology / Q000379:methods*