The Role of the Three Rs in Improving the Planning and Reproducibility of Animal Experiments

SIMPLE SUMMARY: Efforts to improve the design of animal studies have tended to focus on the more mathematical aspects, such as randomization, blocking and statistical analysis. There are, however, many other factors that affect the data from preclinical studies. To improve validity, scientists must collaborate closely with the animal facility involved as soon as the decision to use animals has been made. Such discussions will also help to improve animal welfare, as well as any health and safety issues. A large number of guidelines have been produced over the last 20 years for reporting results in the scientific literature. Comprehensive guidelines for planning animal experiments have been produced more recently, to fulfill this need. These will be described in this paper. A commitment to improving animal welfare, scientific quality, staff care and transparency for all stakeholders will also foster a culture of care around animal research, which benefits all parties. All the Three Rs of Russell and Burch (Replacement, Reduction and Refinement) play a role in the planning and reproducibility of research and testing which may involve animals. ABSTRACT: Training in the design of animal experiments focuses all too often on those aspects which can be approached mathematically, such as the number of animals needed to deliver a robust result, allocation of group size, and techniques such as randomization, blocking and statistical analysis. Important as they are, these are only a small part of the process of planning animal experiments. Additional key elements include refinements of housing, husbandry and procedures, health and safety, and attention at all stages to animal welfare. Advances in technology and laboratory animal science have led to improvements in care and husbandry, better provision of anesthetics and analgesics, refined methods of drug administration, greater competence in welfare assessment and application of humane endpoints. These improvements require continual dialogue between scientists, facility managers and technical staff, a practice that is a key feature of what has become known as the culture of care. This embodies a commitment to improving animal welfare, scientific quality, staff care and transparency for all stakeholders. Attention to both the physical and mental health of all those directly or indirectly involved in animal research is now an important part of the process of planning and conducting animal experiments. Efforts during the last 30 years to increase the internal and external validity of animal experiments have tended to concentrate on the production of guidelines to improve the quality of reporting animal experiments, rather than for planning them. Recently, comprehensive guidelines for planning animal studies have been published, to redress this imbalance. These will be described in this paper. Endorsement of this overarching influence of the Three R concept, by all the stakeholders, will not only reduce animal numbers and improve animal welfare, but also lead to more reliable and reproducible research which should improve translation of pre-clinical studies into tangible clinical benefit.