Systematic reviews of animal research

Zen and the art of systematic reviews

Described the concept of systematic reviews of animal studies, and the First International Symposium on Systematic Reviews in Laboratory Animal Science, hosted by the 3R Research Centre (3RRC) (which then became the SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE)), at the Radboud University Nijmegen Medical Centre, in The Netherlands, February 2012. 

Knight A (2012). Zen and the art of systematic reviews. LASA Forum, Spring, 20-22.

Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare

Abstract

Widespread reliance on animal models during preclinical research and toxicity testing assumes their reasonable predictivity for human outcomes. However, of 20 published systematic reviews examining human clinical utility, located during a comprehensive lit- erature search, animal models demonstrated significant potential to contribute toward the development of clinical interventions in only two cases, one of which was contentious. Included were experiments expected by ethics committees to lead to medical advances, highly- cited experiments published in major journals, and chimpanzee experiments—the species most generally predictive of human outcomes. Seven additional reviews failed to demonstrate utility in reliably predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Results in animal models were frequently equivocal, or inconsistent with human outcomes. Consequently, animal data may not generally be considered useful for these purposes. Regulatory acceptance of non-animal models is normally conditional on for- mal scientific validation. In contrast, animal models are simply assumed to be predictive of human outcomes. These results demonstrate the invalidity of such assumptions. The poor human clinical and toxicological utility of animal models, combined with their generally substantial animal welfare and economic costs, necessitate considerably greater rigor within animal studies, and justify a ban on the use of animal models lacking scientific data clearly establishing their human predictivity or utility.

Knight A (2008). Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare. Reviews Recent Clin Trials, 3(2), 89-96.

Summary

Animal experiments scrutinised: systematic reviews demonstrate poor human clinical and toxicological utility

With French translation

Abstract

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 da- ta 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 A (2007). Animal experiments scrutinised: systematic reviews demonstrate poor human clinical and toxicological utility. ALTEX, 24(4), 320-325.