Venous Thromboembolism Risk Marker Assay

静脉血栓栓塞风险标记测定

• 批准号: 7998652
• 负责人: DAVID Henry FARRELL
• 金额: $ 51.42万
• 依托单位: GAMMA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7998652
• 关键词: Amendment; American Society of Hematology; Anticoagulant therapy; Antithrombins; Biological Assay; Biological Markers; Blood; Blood Clot; Blood coagulation; Businesses; Clinical; Clinical Management; Coagulation Process; Communities; Deep Vein Thrombosis; Detection; Development; Diagnosis; Diagnostic; Disease; Doctor of Philosophy; Enzyme-Linked Immunosorbent Assay; Evaluation; Fibrinogen; Gene Mutation; Goals; Gold; Grant; Guidelines; Hematology; Individual; Institutes; International; Journals; Laboratories; Length; Letters; Malignant Neoplasms; Measurement; Measures; Medicine; Menstruation; Messenger RNA; Methods; Monoclonal Antibodies; National Heart, Lung, and Blood Institute; Normal Range; Oral Contraceptives; Patients; Pennsylvania; Performance; Phase; Physicians; Plasma; Pregnancy; Prevention therapy; Process; Production; Protein C Deficiency; Protein Deficiency; Protein Isoforms; Proteins; Prothrombin; Publishing; Reagent; Recurrence; Request for Proposals; Research; Review Literature; Risk; Risk Assessment; Risk Factors; Risk Marker; Sampling; Sensitivity and Specificity; Technology; Technology Transfer; Testing; Therapeutic; Thromboembolism; Thrombophilia; Time; Triad Acrylic Resin; United States Food and Drug Administration; Universities; Venous; base; college; design; factor V Leiden; forging; genetic risk factor; high throughput screening; improved; insight; interest; non-genetic; novel; programs; public health relevance; scale up

DESCRIPTION (provided by applicant): The application's broad, long-term objectives are to develop a rapid, high-throughput clinical assay for 3' fibrinogen that will be used to assess the risk of a patient developing venous thromboembolism. This assay will guide clinical management, particularly the use of long-term anticoagulant therapy for patients. The utility of this assay will be the identification of patients at risk for developing venous thromboembolism who should be anticoagulated, and conversely, identification of patients at low risk of developing venous thromboembolism who should not be subjected to the possible dangers of anticoagulant therapy. The specific aim of Phase I of this Fast-Track application is to: 1) Develop a rapid, high-throughput assay for 3' fibrinogen. This will be accomplished using our proprietary monoclonal antibody, 2.G2.H9, and the Luminex xMAP(R) technology platform. The milestones for the successful completion of Phase I and transition to Phase II are to develop a 3' fibrinogen assay that measures the normal range of 3' fibrinogen in plasma from 0-1.5 mg/ml, and achieves a standard curve fit with an R2 accuracy of >0.95. In Phase II, the Specific Aims are to: 2) Validate the 3' fibrinogen assay. The assay will be evaluated for linearity, interference testing, method comparison, bias estimation, and comparison to the previous plate-based ELISA in test samples using guidelines published by the Clinical and Laboratory Standards Institute (CLSI) for precision performance of quantitative measurement methods. This information will be essential for Food and Drug Administration (FDA) and Clinical Laboratory Improvement Amendments (CLIA) evaluation of the assay; 3) Quantitate the intra-individual variability of 3' fibrinogen levels over time. This will be accomplished by measuring 3' fibrinogen levels in individuals at weekly time points over a 3-month period and monthly time points over a one-year period to determine the within-subject variability. This information will be critical for widespread acceptance of the assay by clinical laboratories; 4) Scale up production of the assay kit components. This will be accomplished with assistance from the Office of Technology Transfer & Business Development at OHSU, which has forged ties with the entrepreneurial and local business community to create a framework of support for the development of companies utilizing OHSU research. Their Springboard Program is designed to catalyze the development of new ventures based on OHSU technologies. We have already attracted the interest of Diagnostica Stago, a major international coagulation diagnostics company. PUBLIC HEALTH RELEVANCE: This proposal is to develop a rapid, high-throughput clinical assay for 3' fibrinogen, a newly-emerging risk factor for venous thromboembolism. This assay will be used by physicians for risk assessment of venous thromboembolism, and will guide their clinical management, particularly their use of anticoagulant therapy in patients. Information gained from the use of this assay will identify patients at risk for deep vein thrombosis who should be anticoagulated, and conversely, will identify patients at low risk of venous thromboembolism who should not be subjected to anticoagulant therapy.

描述（由申请人提供）：该申请的广泛、长期目标是开发一种快速、高通量的3'纤维蛋白原临床检测方法，用于评估患者发生静脉血栓栓塞的风险。该检测将指导临床管理，特别是对患者使用长期抗凝治疗。该试验的用途是识别有静脉血栓栓塞风险的患者，他们应该抗凝治疗，相反，识别低风险的患者，他们不应该接受抗凝治疗的可能危险。该快速通道申请I期的具体目标是：1)开发一种快速、高通量的3'纤维蛋白原检测方法。这将使用我们专有的单克隆抗体2.G2来完成。H9，以及Luminex xMAP(R)技术平台。成功完成I期并过渡到II期的里程碑是开发3‘纤维蛋白原测定，测量血浆中3’纤维蛋白原的正常范围为0-1.5 mg/ml，并获得R2精度为>.95的标准曲线拟合。在II期，具体目标是：2)验证3'纤维蛋白原测定。将使用临床和实验室标准协会（CLSI）发布的定量测量方法精确性能指南，评估该检测方法的线性度、干扰测试、方法比较、偏倚估计以及与之前基于板的ELISA在测试样品中的比较。这些信息对于美国食品和药物管理局（FDA）和临床实验室改进修正案（CLIA）对该检测的评估至关重要；3)量化3'纤维蛋白原水平随时间的个体内变异性。这将通过在3个月内每周时间点测量个体的3‘纤维蛋白原水平和在一年内每月时间点测量个体的3’纤维蛋白原水平来完成，以确定受试者内部的可变性。这一信息对于临床实验室广泛接受该检测方法至关重要；4)扩大检测试剂盒成分的生产规模。这项工作将在OHSU技术转让和商业发展办公室的协助下完成，该办公室与企业家和当地商界建立了联系，为利用OHSU研究成果的公司发展提供了支持框架。他们的跳板项目旨在促进基于OHSU技术的新企业的发展。我们已经吸引了国际主要凝血诊断公司Diagnostica Stago的兴趣。