Opinion versus evidence for the need to move away from animal testing.

Science is based on facts and their discourse. Willingly or unwillingly, facts are mixed with opinion, i.e., views or judgments formed, not necessarily based on fact or knowledge. This is often necessary, where we have controversial facts or no definitive evidence yet, because we need to take decisions or have to prioritize. Evidence-based approaches aim at identifying the facts and their quality objectively and transparently; they are now increasingly embraced in toxicology, especially by employing systematic reviews, meta-analyses, quality scoring, risk-of-bias tools, etc. These are core to Evidence-based Toxicology. Such approaches aim at minimizing opinion, the "eminence-based" part of science. Animal experiments are the basis of a lot of our textbook knowledge in the life sciences, have helped to develop desperately needed therapies, and have made this world a safer place. However, they represent only one of the many possible approaches to accomplish all these things. Like all approaches, they come with shortcomings, and their true contribution is often overrated. This article aims to summarize their limitations and challenges beside the ethical and economical concerns (i.e., costs and duration as well as costs following wrong decisions in product development): they include reproducibility, inadequate reporting, statistical under-powering, lack of inter-species predictivity, lack of reflection of human diversity and of real-life exposure. Each and every one of these increasingly discussed aspects of animal experiments can be amended, but this would require enormous additional resources. Together, they prompt a need to engineer a new paradigm to ensure the safety of patients and consumers, new products and therapies.