Type 1 Diabetes Trialnet: Operations Coord. Center

这份提案由乔治华盛顿大学生物统计中心提交，作为 试验网运营协调中心回应RFA DK-01-004“1型糖尿病试验网：核心支持” 试验网业务协调中心(OCC)的职能是提供持续的 正在进行的DPT-1肠外和口服胰岛素一级预防试验，并支持未来与 预防1型糖尿病的终极目标及其改善。 据估计，截至1997年，全球约有1.24亿人患有糖尿病，其中 100万人患有1型糖尿病，其中大多数在儿童时期发病。仅在美国，大约 1570万人患有糖尿病，占总人口的5.9%，而美国至少有50万人或0.12%的人患有糖尿病 人口，每1000人1.2人，然后患有1型糖尿病。 1型糖尿病的发病是从受孕那一刻开始的一系列事件中的一步。 遗传多态，主要是人类白细胞抗原单倍型，已经被发现会增加发病风险。 糖尿病，或者是保护性的。遗传缺陷使个人容易对其中一种疾病产生异常的免疫反应 可能存在许多环境侮辱。在环境触发后，T细胞开始攻击胰岛素- 产生胰腺的β细胞或胰岛细胞。这种自身免疫反应表现为抗体和 随后的第一时相胰岛素反应丧失。此后，β细胞功能下降。这使其具有可行性 研究1型糖尿病的遗传学和免疫耐受性，环境病原体的作用， 自身免疫和免疫耐受的特征，发展为糖尿病的风险的评估，以及各种 旨在免疫耐受或保存β细胞功能的干预措施。 乔治华盛顿大学生物统计中心的目标是利用我们的大量资源 和经验，以完成以下主要任务，确保临床和科学的成功 将由TrialNet进行和完成的多方面研究。(1)研究协调和规划：我们将提供帮助 建立高效的组织结构，确保各项活动协调推进。(2)数据 管理活动：我们将应用我们已建立的系统进行持续的数据收集和数据管理，以及 将生成总结审判执行情况的定期报告。(3)统计分析：我们提供 在研究设计方面发挥统计领导作用，并迅速、及时地进行中期和最终分析 举止。(4)文件：我们将有秩序地完成所有研究，并提供完整的文件和 向美国国立卫生研究院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.