Johns Hopkins University, Dept. Environmental Health Sciences, Center for Alternatives to Animal Testing, Baltimore, MD 21205, USA.
ALTEX. 2010;27(4):253-63. doi: 10.14573/altex.2010.4.253.
Validation has become a primary driver of the evolution of toxicological methods. Agreement at OECD level currently requires validation of new approaches for consideration in test guideline development. Several examples of this exist. However, the toxicology in the 21(st) century movement, prompted by the 2007 NRC/NAS vision document, might lead to a revolutionary change in the toxicological toolbox. The challenge is whether the validation process, as it has been formalized over the last two decades, meets the needs for this paradigm shift.The concept of evidence-based medicine (EBM) has emerged from clinical medicine, which retrospectively assesses the evidence of adequacy of a given approach. This is not typically done in prospective studies - the equivalent of validation studies might be multicenter randomized trials. Evidently, where such unambiguous evidence is available, no other assessment is necessary. EBM, however, has developed procedures, including meta-analysis, to collect and evaluate all the available evidence where no such definitive study is available. The recent successful introduction of retrospective validation, i.e. the collection and evaluation of existing evidence from various sources, represents a step in this direction. Here, we will explore new toxicological approaches via evidence-based toxicology (EBT).
验证已成为毒理学方法发展的主要驱动力。目前，经合组织（OECD）层面要求对新方法进行验证，以供测试指南制定时参考。这方面有几个例子。然而，由 2007 年 NRC/NAS 远景文件引发的 21 世纪毒理学运动，可能会使毒理学工具箱发生革命性变化。面临的挑战是，在过去二十年中正式形成的验证过程是否满足这一范式转变的需求。循证医学（EBM）的概念源自临床医学，它对给定方法的充分性证据进行回顾性评估。这在前瞻性研究中通常不会进行——相当于验证研究的可能是多中心随机试验。显然，在有明确证据的情况下，不需要进行其他评估。然而，EBM 已经开发了一些程序，包括荟萃分析，以收集和评估所有可用的证据，而没有这样的明确研究。最近成功引入了回顾性验证，即从各种来源收集和评估现有证据，这是朝着这个方向迈出的一步。在这里，我们将通过循证毒理学（EBT）探索新的毒理学方法。
