UT Southwestern: Clinical Site for the Drug-Induced Liver Injury Network

描述(由申请人提供)： 药物性肝损伤(DILI)是临床医学面临的难题之一。意想不到的帝力阻碍了多种有效药物的药物开发。许多药物已获得批准或几乎获得批准，但由于严重的、有时是致命的DILI，未能获得广泛接受。审批前试验的规模很小，这意味着不会捕获不常见的事件。因此，积极、有力和有节制的方法对药物引起的不良事件及其特征进行上市后监测对所有美国人的健康至关重要。药物诱导的肝损伤网络(DILIN)在最初的5年里在奠定基础方面已经有了一个强有力的开端，建立了在未来可以更广泛使用的系统。因此，有机会加强对更多的上市后帝力案件的捕获，以便更好地了解其原因和。潜在的，它的治疗。德克萨斯大学西南分校非常适合成为DILIN选址，原因如下：1)达拉斯沃斯堡大都会建筑群由超过650万人口的多元化城市/郊区人口组成。2)研究人员在DILI和临床试验开发方面具有特定和强大的经验，我们的具体建议包括：1)建立该地区的临床医生咨询委员会，以转诊病例。我们将经常咨询他们，为他们的电话提供1-800号码，并访问网站，了解服务中的最新情况，并讨论导致DILI的重要药物。2)我们将利用研究人员在急性肝功能衰竭研究中的经验，扩大和鼓励进一步利用DILI生物材料进行辅助研究。对于我们机构目前正在研究的大量拉美裔人口，具体的子研究应该是可能的。3)我们提出了一项使用N-乙酰半胱氨酸的治疗试验，用于符合严重损伤标准的DILI病例，接近Hy Zimmerman定律，即伴随黄疸的急性疾病。

DESCRIPTION (provided by applicant): Drug-induced liver injury (DILI) is one of the most difficult problems encountered in clinical medicine. Unexpected DILI has hampered drug development for a multitude of effective drugs. Many agents have been approved or nearly approved but failed to gain widespread acceptance because of severe and sometimes fatal DILI. The small size of pre-approval trials means that infrequent events will not be captured. Thus, aggressive, robust, and measured approaches to post-marketing surveillance for adverse events due to drugs and their characterization is vital to the health of all Americans. The Drug-Induced Liver Injury Network (DILIN) has made a strong start in laying the groundwork in its first 5 years, having put in place systems that can be used more widely in the future. Thus, an opportunity exists to enhance capture of additional cases of post-marketing DILI so as to improve our understanding of its causes and. potentially, its treatment. UT Southwestern is ideally suited to become a DILIN site for the following reasons: 1) the Dallas Fort Worth metroplex constitutes a widely diverse urban/suburban population of over 6.5 million people. 2) the investigators have specific and strong experience in DILI and clinical trials development, Our specific proposals include: 1) An advisory board of clinicians in the region to refer cases. We will consult them frequently, provide a 1-800 number for their calls and visit sites for in service updates and discussion of drugs of importance in causing DILI. 2) We will utilize the experience of the investigators in the Acute Liver Failure Study to expand and encourage further ancillary studies utilizing DILI biomaterials. Specific substudies should be possible with the large Hispanic population currently under study at our institution. 3) We propose a therapeutic trial using N-acetylcysteine for DILI cases that meet criteria for severe injury approximating Hy Zimmerman's law, that is, an acute illness with attendant jaundice.