新一代致癌性风险评估的计算机决策支持系统

IF 2.9 3区 医学 Q2 TOXICOLOGY
S. Stalford
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引用次数: 0

摘要

ICH S1B(R1)附录是改进人类相关致癌性检测的一个重要里程碑。利用证据权重(WoE)评估中的相关数据和知识,现在可以用来确定一项为期两年的大鼠研究是否会增加药物安全一揽子计划的价值。最近的出版物描述了在实际执行经修订的指南方面的经验,强调了最初应用这种方法所带来的机遇和挑战,例如数据差距、文件和解释。这些反思强调了制定最佳实践和建立框架的重要性,以确保新法规能够以科学严谨的方式一致和透明地应用,以支持化学品安全决策。计算机决策支持系统通过组织证据、编码指导和实现最佳实践,提供了实现这一目标的手段。使用该决策支持系统进行了案例研究,以实现ICH S1B(R1)增补决策。该系统能够从ICH指南和新出现的最佳实践中获取要求。此外,相关的数据和知识是围绕AOP网络组织的,从而将证据置于上下文环境中,并带来透明度和一致性。有了这一点,指导专家审查就可以让用户关注需要额外信息或审查的地方,以减少不确定性。总体而言,决策支持系统能够为复杂的WoE评估提供系统、透明和可靠的结果,从而支持各组织在达成的决策中达成更大的共识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
S04-04 In Silico Decision Support Systems Enabling Next Generation Risk Assessments for Carcinogenicity
The ICH S1B(R1) addendum represents a significant milestone in improving human-relevant carcinogenicity testing. Utilizing relevant data and knowledge in a weight-of-evidence (WoE) assessment can now be used to determine if a two-year rat study would add value to a pharmaceutical safety package. Recent publications describing experiences in the practical implementation of the amended guidance have highlighted both opportunities and challenges from the initial application of this approach such as data gaps, documentation and interpretation. These reflections highlight the importance of developing best practice and having frameworks in place to ensure that the new regulation can be applied consistently and transparently with scientific rigour to support chemical safety decisions.
In silico decision support systems provide a means of achieving this, through organising evidence, encoding guidance, and enabling best practices. A case study was performed using such a decision support system to enable an ICH S1B(R1) addendum decision. The system was able to capture the requirements from the ICH guidance and emerging best practice. In addition, relevant data and knowledge was organised around an AOP network, thus contextualising the evidence and bringing transparency and consistency. With this in place, guided expert review can then focus a user on where additional information or review is needed to reduce uncertainty. Overall, the decision support system enables systematic, transparent and robust outcomes for complex WoE assessments and thus supports greater consensus between organisations in the decisions reached.
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来源期刊
Toxicology letters
Toxicology letters 医学-毒理学
CiteScore
7.10
自引率
2.90%
发文量
897
审稿时长
33 days
期刊介绍: An international journal for the rapid publication of novel reports on a range of aspects of toxicology, especially mechanisms of toxicity.
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