IU Clinical Center: Drug Induced Liver Injury Network

描述（由申请人提供）： 本申请是为了回应RFA DK-07-012而提交的，RFA DK-07-012征求合格研究者的申请，以继续和扩展药物性肝损伤网络（DILIN）。印第安纳州大学是创始成员之一，也是顶级招聘网站，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在下一个资助期内还将专注于开发或支持机制和治疗辅助研究，开发和验证最佳因果关系工具，并与NLM一起构建权威的肝毒性数据库。我们提出以下具体目标，以实现本RFA的目标。具体目标#1：将大量符合条件的疑似DILI成人和儿童入组正在进行的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前瞻性和回顾性疑似DILI病例，每个病例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内外研究者的机制（遗传和非遗传）和治疗辅助研究的开发和支持。我们建议在下一个资助期内，在具有良好特征的DILI患者中进行一项全身性类固醇治疗的网络范围内的辅助性试点研究。具体目标3：继续以稳健的方式参与我们正在进行的研究中入组的疑似DILI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。我们的作用将在概念、方法、业务和背景层面上广泛发挥。具体目标5：其目标是与其他DILIN研究人员一起，建立一个DILI国际联盟，以促进思想交流、命名标准化、合作研究以及相互观察和发现的交叉验证。

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.