How Can Systematic Reviews Teach Us More about the Implementation of the 3Rs and Animal Welfare?

SIMPLE SUMMARY: The three Rs stand for Replacement, Reduction, and Refinement of animal studies and were published for the first time in 1959 by Russell and Burch. Replacement refers to avoiding the use of (non-human) animals in research. Reduction implies using fewer animals, for example, by better statistical methods and better literature studies, and Refinement means reducing the discomfort and improving the welfare of animals used in experiments. The three Rs have gained more interest and popularity since the 1970s, and have now become the crucial central element in the revised legislation in Europe, the EU Directive 2010/63EU, controlling the proper use of animals in experiments in the European member states. Animals are used in order to improve the health and welfare of other non-human animals, in veterinary medicine, and of humans, for toxicological purposes and in clinical medicine. Using animals in experiments has always been subject to ethical and societal debate. At Syrcle, we have introduced the methodology of systematic reviews for preclinical animal studies since 2012. This methodology comes from the clinical field and is a key element in evidence-based medicine, as systematic reviews summarise the scientific evidence as objectively as possible. A systematic review (SR) is defined as a literature review focused on a single question that tries to identify, appraise, select, and synthesise all high-quality research evidence relevant to that question. Introducing this methodology for the preclinical animal studies seems very logical, as animal studies in clinical medicine are performed for protecting humans from ineffective or unsafe treatments. Systematic reviews thus lead to summarising evidence from preclinical studies before entering clinical trials. In addition to protecting humans, systematic reviews can also be used to implement the three Rs. Examples of how systematic reviews contribute to implementing the three Rs are provided in the following article, thus demonstrating the value for protecting animals as well. ABSTRACT: This paper describes the introduction of the systematic review methodology in animal-based research and the added value of this methodology in relation to the 3Rs and beyond. The 3Rs refer to Replacement, Reduction, and Refinement of animal studies. A systematic review (SR) is defined as a literature review focused on a single question that tries to identify, appraise, select, and synthesise all high-quality research evidence relevant to that question. Examples are given on how SRs lead to the implementation of the 3Rs and better science. Additionally, a broader context is given regarding societal, political, and scientific developments. Various examples of systematic reviews are given to illustrate the current situation regarding reporting, quality, and translatability of animal-based research. Furthermore, initiatives that have emerged to move further towards more responsible and sustainable research is of benefit for both animals and humans.