IU Clinical Center: Drug Induced Liver Injury Network

描述(由申请人提供)： 本申请是应RFA DK-07-012向有资格的调查人员征集继续和扩大药物性肝损伤网络(DILIN)的申请而提交的。印第安纳大学是DILIN的创始成员之一，也是顶尖的招聘网站，自成立以来一直积极参与DILIN的所有业务。除了加速受试者招募，DILIN在下一个资助期还将专注于开发或支持机械性和治疗性辅助研究，开发和验证最佳因果关系工具，并与NLM共同构建一个权威的肝毒性数据库。我们提出以下具体目标，以实现本论坛的目标。具体目标1：将大量符合条件的疑似DILI成人和儿童纳入正在进行的DILIN前瞻性和回顾性研究。我们建议从印第安纳州中部的多个传统和独特来源收集未来和回顾的疑似DILI病例，每个来源都提供独特的流行病学方面和研究潜力。具体目标#2：积极参与DILIN内外研究人员对机械性(遗传和非遗传)和治疗性辅助研究的开发和支持。我们建议在下一个资助期进行一项网络范围内的系统性类固醇激素对特征良好的DILI患者的治疗辅助试点研究。具体目标3：继续以强有力的方式参与我们正在进行的研究中登记的帝力疑似病例的因果关系评估，并在开发和验证最佳和用户友好的新因果关系工具(S)方面发挥重要作用。具体目标4：与利益相关者共同开发一个权威的DILI电子数据库，并为执业医生和公众开展宣传和教育活动。我们将在概念、方法、业务和背景层面发挥广泛的作用。具体目标#5：目标是与其他DILIN调查人员一起发展一个帝力国际联合会，以促进思想交流、术语标准化、合作研究和相互验证对方的观察和发现。

DESCRIPTION (provided by applicant): This application is submitted in response to RFA DK-07-012 which solicits applications from qualified investigators for the continuation and expansion of the Drug Induced Liver Injury Network (DILIN). Indiana University, one of the founder members and a top recruitment site, has robustly participated in all DILIN operations since its inception. In addition to accelerated subject recruitment, the DILIN during the next funding period will also focus on developing or supporting mechanistic and therapeutic ancillary studies, developing and validating optimal causality instruments and constructing in conjunction with NLM an authoritative hepatotoxicity database. We propose the following specific aims to meet the goals of this RFA. Specific Aim # 1: To enroll large number of eligible adults and children with suspected DILI into ongoing DILIN prospective and retrospective studies. We propose to collect prospective and retrospective cases of suspected DILI from multiple traditional as well as unique sources in Central Indiana, each providing distinctive epidemiological facets and research potential. Specific Aim # 2: To robustly participate in the development and the support of mechanistic (genetic and non-genetic) and therapeutic ancillary studies by investigators within and outside the DILIN. We propose to conduct a network wide therapeutic ancillary pilot study of systemic steroids in patients with well characterized DILI during the next funding period. Specific aim # 3: To continue to participate in a robust fashion in the causality assessment of suspected DILI cases that are enrolled into our ongoing studies and to play a major role in developing and validating new causality instrument(s) that are optimal and user-friendly. Specific aim # 4: To develop, in conjunction with stake holders, an authoritative electronic DILI database, and outreach and educational activities for practicing physicians and the public. Our role will be extensive at conceptual, methodological, operational and contextual levels. Specific aim # 5: The objective is to develop, in conjunction with other DILIN investigators, an international consortium of DILI to facilitate exchange of ideas, standardization of nomenclature, collaborative studies and cross validation of each other's observations and discoveries.