Critically evaluating animal research

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 literature search, animal models demonstrated significant potential to contribute toward 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. The likely causes of the poor human clinical and toxicological utility of animal models include inherent genotypic and phenotypic differences between human and non-human species, the distortion of experimental outcomes arising from stressful experimental environments and protocols, and the poor methodological quality of most animal experiments. To ensure good methodological quality, animal research protocols should routinely utilize principles such as those contained within the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. These include the random allocation of animals to experimental groups, blinded assessment of outcome measures, statistical justifications of sample sizes, reporting of animals excluded from analyses, and of exclusion criteria, and of any investigator conflicts of interest. Adherence to such principles minimizes the potential for bias and maximizes the reliability of research results. Nevertheless, even following the endorsement or publication of the ARRIVE guidelines by over 300 research journals beginning in 2010, severe deficiencies of experimental design remain the norm. Disturbingly, these deficiencies are apparent in research conducted at leading UK universities, in research funded by leading UK funding organisations, and in research reported in high impact journals. Problems arising from stressors and poor methodological quality might theoretically be minimised, although fundamental changes to the practice of laboratory animal science would be required, given their widespread prevalence. However, limitations resulting from interspecies differences are likely to remain technically and theoretically impossible to overcome. Furthermore, invasive laboratory animal use is increasingly inconsistent with our growing understanding of the psychological and social characteristics of laboratory animal species, including their ability to experience suffering and pleasure; of the impacts resulting from laboratory environments and procedures; and of the moral obligations that unavoidably stem from such knowledge. Invasive animal research consumes the lives of millions of sentient animals, as well as very substantial scientific and financial resources-all of which are subsequently unavailable to other research fields. Poor experimental design may result in misleading research results, allowing ineffective treatments and unjustified optimism, and delaying effective treatments, for human patients. Accordingly, a paradigm change in scientific animal use is clearly warranted. Instead of uncritically assuming the benefits to human healthcare of such research, we must subject it to rigorous and critical evaluation. Where such research does not meet the cost-benefit criteria expected by society, and underpinning policy instruments such as Directive 2010/63/EU on the protection of animals used for scientific purposes, it must cease, with the resources consumed by it directed into more promising and justifiable fields of research and healthcare. Where such research continues to persist, a broad range of measures must be implemented to minimize laboratory animal stress, and to maximize the reliability of research results.