Biostatistics and Data Management

生物统计学和数据管理

• 批准号: 10493798
• 负责人: Haesook T Kim
• 金额: $ 27.65万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10493798
• 关键词: Acute Graft Versus Host Disease; Allogenic; Animals; B-Lymphocytes; Biometry; Blinded; Blood; Bronchiolitis Obliterans; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Complex; Data; Data Analyses; Data Element; Databases; Disease; Ensure; Epitopes; Fibrosis; Functional disorder; Goals; Immune; Immune Targeting; Immune system; Immunologics; Impairment; Laboratories; Laboratory Research; Laboratory Study; Lung; Maintenance; Malignant Neoplasms; Manuscripts; Mediating; Morbidity - disease rate; Organoids; Outcome; Pathway interactions; Patients; Phase II Clinical Trials; Policies; Prevention therapy; Principal Investigator; Procedures; Protocols documentation; Pulmonary Fibrosis; Quality Control; Quality of life; Recurrent disease; Reporting; Research Design; Research Infrastructure; Research Personnel; Research Project Grants; Resource Sharing; Services; Standardization; Statistical Data Interpretation; Syndrome; T-Lymphocyte; Therapeutic; Therapeutic Agents; Time; Translational Research; Writing; cellular targeting; chronic graft versus host disease; computerized data processing; computing resources; data management; graft vs host disease; graft vs leukemia effect; hematopoietic cell transplantation; inhibitor; laboratory experiment; lung injury; mortality; novel therapeutics; operation; programs; research study; response; therapeutic target; translational study

Project Summary Allogeneic hematopoietic cell transplantation (HCT) is a long-established therapy for blood malignancies. The therapeutic benefit and potential cure achieved by HCT is mediated by the graft-vs-leukemia (GVL) effect that is derived from donor immune system. However, the full recognition of the GVL effect has been hampered by disease relapse and graft-versus-host disease (GVHD). The overarching objective of the research projects in this application is to better understand the complex pathophysiology of chronic GVHD, the mechanisms leading to fibrosis and lung injury, and to develop therapeutics targeting the major pathways leading to the common clinical manifestations of chronic GVHD. More specifically, Project 1 will identify immune networks that characterize patients who will develop cGVHD and interrogate mechanisms of response to various treatments for chronic GVHD; Project 2 will be dedicated to develop into bronchiolitis obliterans and lung fibrosis to identify new therapeutic agents to treat lung chronic GVHD; and Project 3 will perform a phase II clinical trial of a ROCK2 inhibitor to treat lung cGVHD, identify the cellular target of immunologic attack in bronchiolitis obliterans syndrome (BOS) using lung organoids, and identify the antigenic determinants of immune attack in BOS. Project 1 involves various translational studies to identify a immunologic signature for cGVHD, Project 2 involves animal studies and Project 3 involves both a clinical trial as well as translational studies to achieve the overarching goal of this application. The primary objective of the Biostatistics and Data Management Core (Core 3) is to provide statistical collaboration for all investigators involved in this Program Project. This includes collaboration with project investigators in the design of clinical trial and laboratory studies, analysis of clinical and laboratory data and to establish correlations of clinical outcomes with laboratory results, and participate in manuscript writing in all Projects. Core 3 will also provide centralized mechanisms to assure the timely and complete capture of all clinical data in this Program Project. This includes collection and maintenance of necessary clinical information, data management support, quality control for clinical data, and oversight of clinical trial operations to ensure that all data elements required by each protocol are collected in timely fashion; and where necessary, design of research procedures and databases to allow blinded laboratory assessments and later integration with patient- level data for analysis.

项目摘要 异基因造血细胞移植（HCT）是一种治疗血液恶性肿瘤的长期治疗方法。的 HCT获得的治疗益处和潜在治愈是由移植物抗白血病（GVL）效应介导的， 来源于捐赠者的免疫系统。然而，对GVL效应的充分认识受到以下因素的阻碍： 疾病复发和移植物抗宿主病（GVHD）。研究项目的总体目标是 本申请旨在更好地了解慢性GVHD的复杂病理生理学， 纤维化和肺损伤，并开发针对主要途径的治疗方法， 慢性GVHD的临床表现。更具体地说，项目1将识别免疫网络， 描述将发生cGVHD的患者，并询问对各种治疗的反应机制 慢性GVHD;项目2将致力于发展为闭塞性细支气管炎和肺纤维化，以确定 治疗肺部慢性GVHD的新治疗药物;项目3将进行ROCK 2的II期临床试验 抑制剂治疗肺部cGVHD，确定闭塞性细支气管炎免疫攻击的细胞靶点 综合征（BOS）使用肺类器官，并确定BOS中免疫攻击的抗原决定簇。项目 1涉及各种翻译研究，以确定cGVHD的免疫特征，项目2涉及动物 研究和项目3涉及临床试验以及转化研究，以实现总体目标 这个应用程序。生物统计和数据管理核心（核心3）的主要目标是提供 参与本计划项目的所有研究者的统计协作。其中包括与 临床试验和实验室研究的设计，临床和实验室数据的分析 并建立临床结果与实验室结果的相关性，并参与论文撰写， 所有项目。核心3还将提供集中机制，以确保及时和完整地收集所有 本计划项目中的临床数据。这包括收集和维护必要的临床信息， 数据管理支持、临床数据质量控制和临床试验操作监督，以确保 及时收集每个方案所需的所有数据元素;必要时， 研究程序和数据库，以允许盲态实验室评估和随后与患者整合- 水平数据进行分析。