Type 1 Diabetes Trialnet: Operations Coord. Center

该提案由乔治华盛顿大学生物统计中心提交， TrialNet运营协调中心回应RFA DK-01-004“1型糖尿病TrialNet：核心支持 设施“TrialNet的操作协调中心（OCC）的职能是提供 正在进行的DPT-1胃肠外和口服胰岛素一级预防试验，并支持未来的研究， 预防和改善1型糖尿病的最终目的。 截至1997年，估计全世界约有1.24亿人患有糖尿病，其中3.5 1型糖尿病的发病率为1000万，其中大多数在儿童时期发病。仅在美国，大约 15.7 100万人，或总人口的5.9%患有糖尿病，其中至少50万人或0.12%的美国人患有糖尿病。 1型糖尿病的发病率为1.2/1000。 1型糖尿病的发病是从受孕开始的一连串事件中的一步。 遗传多态性，主要是HLA单倍型，已被确定为增加发展中国家的风险。 遗传缺陷使个体容易对一种疾病产生异常的免疫反应， 可能有很多环境污染。随着环境的触发，T细胞开始攻击胰岛素- 产生胰腺的β或胰岛细胞。这种自身免疫反应表现为抗体的出现， 第一时相胰岛素反应的丧失。此后，β细胞功能下降。这使得它可行， 进行1型糖尿病和免疫耐受的遗传学研究，环境病原体的作用， 自身免疫和免疫耐受的表征，发展糖尿病的风险评估，以及各种 干预措施旨在免疫耐受或保护β细胞功能。 乔治华盛顿大学生物统计中心的目标是运用我们的大量资源 和经验，以完成以下主要任务，以确保临床和科学的成功， 将由审判网进行和完成多方面的研究。(1)研究协调和规划：我们将提供帮助 建立一个有效的组织结构，以确保所有活动以协调的方式推进。(2)数据 管理活动：我们将应用我们建立的系统进行持续的数据收集和数据管理， 将生成总结试验执行情况的定期报告。(3)统计分析：我们将提供 在研究设计中发挥统计领导作用，并迅速及时地进行中期和最终分析。 方式(4)文件：我们将提供完整的文件，有序关闭所有研究， 向NIH和公众传播相关材料。

This proposal is submitted by The Biostatistics Center of The George Washington University to serve as the Operations Coordinating Center for TrialNet in response to RFA DK-01-004 "Type 1 Diabetes TrialNet: Core Support Facilities." The functions of the Operations CoordinatingCenter (OCC) for TrialNet are to provide for thecontinuation of the ongoing DPT-1 parenteral and oral insulin primary prevention trials and to support future studies with the ultimate objective of prevention of type 1diabetes and its amelioration. As of 1997 it is estimated that worldwide about 124 million individuals had diabetes mellitus, of which 3.5 million have type 1 diabetes, the majority of these having an onset during childhood. In the US alone,approximately 15.7 million individuals, or 5.9% of the total population have diabetes, with at least 500,000 or 0.12% of the US population, 1.2 per 1000 population, then having type 1 diabetesmellitus. The onset of type 1 diabetes mellitus is one step in a chain of events that begins at the moment of conception. Genetic polymorphisms,principallyHLA haplotypes, have been identified that confer an increased risk of developing diabetes, or are protective.Genetic defects render an individual susceptible to an aberrant immunologicresponse to one of possibly many environmental insults. Following the environmental trigger, the T-cells begin an assault on the insulin- producing beta or islet cells of the pancreas. This autoimmuneresponse is manifest by the appearance of antibodies and the subsequent loss of first phase insulin response. Thereafter beta cell function declines. This makes it feasible to conduct studies of the genetics of type 1 diabetes and immune tolerance, the role of environmental pathogens, the characterization of autoimmunity and immune tolerance, evaluation of the risk of developing diabetes, and various interventions aimed at immune tolerance or preservation of beta cell function. The objective of The George Washington University Biostatistics Center is to apply our considerable resources and experience to the completion of the following main tasks to ensure the clinical and scientific success of the multifaceted studies to be undertaken and completed by TrialNet. (1) Study Coordination and Planning: We will help establish an efficient organizational structure to ensure that all activities advance in a coordinated fashion. (2) Data Management Activities: We will apply our established systems for on-going data collection and data management, and will generate periodic reports summarizing the execution of the trial. (3) Statistical Analysis: We will provide statistical leadership in the design of studies, and perform interim and final analyses in an expeditious and timely manner. (4) Documentation: We will provide for the orderly closeout of all studies with complete documentation and dissemination of relevant materials to the NIH and the public.