Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014.
Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014.
复制标题
DOI：
10.1002/hep.27720
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Friedman SL
中科院分区：
文献类型：
--
作者：
Torok NJ;Dranoff JA;Schuppan D;Friedman SL
慢性肝病急需开发抗纤维化疗法，并明确抗纤维化试验中的哪些终点能被监管机构接受。美国肝病研究协会（AASLD）主办了一次终点会议，以帮助加速抗纤维化药物的有效测试，并就肝纤维化的临床试验设计提出建议。在这篇综述中，我们总结了此次会议的重要和新颖内容，并为未来的临床试验设计提供了方向。本文遵循会议的结构，分为五个部分：I）抗纤维化试验设计；II）临床前概念验证研究；III）药理靶点：基本原理和经验教训；IV）合理的药物设计与开发；V）肝纤维化临床试验设计的共识与建议。专家综述和协作讨论有助于总结关键的未满足需求和未来方向，包括：1）更明确高危人群和研究群体；2）药物研发和测试所有要素的标准化；3）临床试验方法的标准化；4）加速开发改进的非侵入性标志物；5）需要探索未来抗纤维化药物潜在的脱靶毒性。
There is an urgent need to develop antifibrotic therapies for chronic liver disease, and to clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. AASLD sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and to develop recommendations on clinical trial design for liver fibrosis. In this review we summarize the salient and novel elements of this conference and provide directions for future clinical trial design. The paper follows the structure of the conference and is organized into five areas: I) Antifibrotic trial design; II) Preclinical proof of concept studies; III) Pharmacologic targets: rationale and lessons to learn; IV) Rational drug design and development; V) Consensus and recommendations on design of clinical trials in liver fibrosis. Expert overviews and collaborative discussions helped to summarize the key unmet needs and directions for the future, including: 1) Greater clarification of at-risk populations and study groups; 2) Standardization of all elements of drug discovery and testing; 3) Standardization of clinical trial approaches; 4) Accelerated development of improved non-invasive markers; 5) Need for exploration of potential off-target toxicities of future antifibrotic drugs.