Hartung Thomas
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA.
University of Konstanz, CAAT-Europe, Konstanz, Germany.
ALTEX. 2017;34(2):193-200. doi: 10.14573/altex.1703291.
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.
科学基于事实及其论述。无论愿意与否，事实中都夹杂着观点，即不一定基于事实或知识而形成的看法或判断。在我们面对有争议的事实或尚无确凿证据的情况下，这往往是必要的，因为我们需要做出决策或进行优先级排序。循证方法旨在客观、透明地识别事实及其质量；如今在毒理学中越来越受到青睐，特别是通过采用系统评价、荟萃分析、质量评分、偏倚风险工具等。这些是循证毒理学的核心。此类方法旨在尽量减少观点，即科学中“基于权威”的部分。动物实验是我们生命科学许多教科书知识的基础，有助于开发急需的疗法，并使这个世界变得更安全。然而，它们只是实现所有这些目标的众多可能方法之一。与所有方法一样，它们也有缺点，其真正贡献往往被高估。本文旨在总结其局限性和挑战，以及伦理和经济方面的问题（即成本和持续时间以及产品开发中错误决策后的成本）：这些问题包括可重复性、报告不充分、统计效力不足、缺乏种间预测性、缺乏对人类多样性和现实生活暴露的反映。动物实验中每一个这些越来越受关注的方面都可以改进，但这需要大量额外资源。总体而言，它们促使我们需要设计一种新的范式，以确保患者和消费者、新产品和疗法的安全。
