Sample Collection and Analysis to Expand Demographics Diversity of Reference Range for the Final Qualification Package for GLDH Activity as a Biomarker of Drug Induced Liver Injury (DDT-BMQ-000050)

摘要 这个项目旨在增加我们对谷氨酸正常参考范围的理解 脱氢酶（GLDH）在儿科，老年人，和扩大种族正常健康 这将解决药物开发中未得到满足的需求， 监测药物性肝损伤（DILI）。这个项目产生的证据是 支持食品药品监督管理局对GLDH的资格认证所必需的 (FDA的）生物标志物鉴定程序（BQP）。这项鉴定工作由 预测安全性测试联盟的肝毒性工作组，GLDH作为一个 用于检测DILI的安全性生物标志物已纳入生物标志物鉴定程序。为了 进入下一阶段的资格认证，肝毒性工作组必须准备一份 总结GLDH在确证性试验中性能的最终确认包 支持生物标志物正在考虑的拟议使用背景的研究 资格认证计划。迄今为止，肝毒性工作组尚未定义 在这些人群中GLDH的正常参考范围，也没有在出版的文献中发现 文学为了弥补这一差距，关键路径研究所（C-Path）提出了以下建议 研究目的。具体目标1将进行一项研究，从健康人群中收集样本， 在100个原始研究中代表性不足的其他年龄组的个体 正常健康志愿者（男性和女性; 50名儿童和50名老年人），来自 United States（US）.该研究将从大学的受试者中收集单个样本， 去密歇根医院做常规检查。此外，具体目标2是进行一项研究， 从健康个体中采集样本，以扩大原始样本中代表性不足的种族 研究报告，这些研究报告将支持今后提交滴滴涕资格鉴定计划# DDTBMQ 000050，以进一步了解不同人群中的GLDH。

ABSTRACT This project seeks to increase our understanding of the normal reference range of glutamate dehydrogenase (GLDH) in pediatric, geriatric, and expanded ethnic normal healthy populations, which will address an unmet need in drug development for detecting and monitoring drug-induced liver injury (DILI). The evidence generated by this project is necessary to support the qualification of GLDH by the Food and Drug Administration’s (FDA’s) Biomarker Qualification Program (BQP). This qualification effort is being led by the Predictive Safety Testing Consortium’s Hepatotoxicity Working Group, for which GLDH as a safety biomarker to detect DILI was into the Biomarker Qualification Program. In order to progress to the next stage of qualification, the Hepatotoxicity Working Group must prepare a Final Qualification Package which summarizes the performance of GLDH in the confirmatory studies to support the proposed context of use under consideration by the Biomarker Qualification Program. To date, the Hepatotoxicity Working Group has not defined the normal reference range of GLDH in these populations, nor has it been found in the published literature. To address this gap, the Critical Path Institute (C-Path) proposes the following research aims. Specific Aim 1 will conduct a study to collect samples from healthy individuals spanning additional age groups under-represented in the original studies in 100 normal healthy volunteers (both male and female; 50 pediatric and 50 geriatric), from the United States (US). The study will collect single samples from subjects at the University of Michigan Hospital for routine visits. In addition, Specific Aim 2 is to conduct a study to collect samples from healthy individuals to expand ethnicities under-represented in the original studies, which will support the future submission of a Qualification Plan for DDT# DDTBMQ000050 in order to further the understanding of GLDH in various populations.