Abstract：
Complex in vitro models (CIVMs) offer the potential to increase the clinical relevance of preclinical efficacy and toxicity assessments and reduce the reliance on animals in drug development. The European Society of Toxicologic Pathology (ESTP) and Society for Toxicologic Pathology (STP) are collaborating to highlight the role of pathologists in the development and use of CIVM. Pathologists are trained in comparative animal medicine which enhances their understanding of mechanisms of human and animal diseases, thus allowing them to bridge between animal models and humans. This skill set is important for CIVM development, validation, and data interpretation. Ideally, diverse teams of scientists, including engineers, biologists, pathologists, and others, should collaboratively develop and characterize novel CIVM, and collectively assess their precise use cases (context of use). Implementing a morphological CIVM evaluation should be essential in this process. This requires robust histological technique workflows, image analysis techniques, and needs correlation with translational biomarkers. In this review, we demonstrate how such tissue technologies and analytics support the development and use of CIVM for drug efficacy and safety evaluations. We encourage the scientific community to explore similar options for their projects and to engage with health authorities on the use of CIVM in benefit-risk assessment.
摘要：
复杂的体外模型（CIVMs）提供了增加临床前疗效和毒性评估的临床相关性并减少药物开发中对动物的依赖的潜力。欧洲毒理学病理学会（ESTP）和毒理学病理学会（STP）正在合作，以强调病理学家在CIVM开发和使用中的作用。病理学家接受了比较动物医学的培训，这增强了他们对人类和动物疾病机制的理解，从而使它们在动物模型和人类之间架起桥梁。此技能对于CIVM开发非常重要，验证,和数据解释。理想情况下,不同的科学家团队，包括工程师,生物学家,病理学家,和其他人,应该合作开发和表征novelCIVM，并共同评估它们的精确用例（使用上下文）。在此过程中，实施形态学CIVM评估应该是必不可少的。这需要强大的组织学技术工作流程，图像分析技术，并且需要与翻译生物标志物相关。在这次审查中,我们展示了这些组织技术和分析如何支持CIVM在药物疗效和安全性评估中的开发和使用.我们鼓励科学界为他们的项目探索类似的选择，并与卫生当局就CIVM在利益风险评估中的使用进行接触。
