Venous Thromboembolism Risk Marker Assay

静脉血栓栓塞风险标记测定

• 批准号: 8131995
• 负责人: DAVID Henry FARRELL
• 金额: $ 52.03万
• 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 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8131995
• 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 Isoforms; Protein S Deficiency; 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' 纤维蛋白原临床测定方法，用于评估患者发生静脉血栓栓塞的风险。该测定将指导临床管理，特别是患者长期抗凝治疗的使用。该测定的用途是识别有发生静脉血栓栓塞风险且应接受抗凝治疗的患者，反之，识别发生静脉血栓栓塞风险较低且不应承受抗凝治疗可能危险的患者。该快速通道应用第一阶段的具体目标是： 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.H9 和 Luminex xMAP(R) 技术平台来实现。成功完成第一阶段和过渡到第二阶段的里程碑是开发一种 3' 纤维蛋白原测定法，测量血浆中 3' 纤维蛋白原的正常范围为 0-1.5 mg/ml，并实现与 R2 拟合的标准曲线准确度 >0.95。在第二阶段，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研究所 (CLSI) 发布的定量测量方法精确性能指南，对测试样品中的线性、干扰测试、方法比较、偏差估计以及与之前基于板的 ELISA 的比较进行评估。该信息对于美国食品药品监督管理局 (FDA) 和临床实验室改进修正案 (CLIA) 的检测评估至关重要； 3) 定量分析 3' 纤维蛋白原水平随时间的个体内部变异性。这将通过在 3 个月期间的每周时间点和一年期间的每月时间点测量个体的 3' 纤维蛋白原水平来确定受试者内的变异性来实现。这些信息对于临床实验室广泛接受该检测至关重要； 4) 扩大检测试剂盒成分的生产。这将在 OHSU 技术转让和业务发展办公室的协助下完成，该办公室与企业家和当地商业界建立了联系，为利用 OHSU 研究的公司的发展创建了一个支持框架。他们的 Springboard 计划旨在促进基于 OHSU 技术的新企业的发展。我们已经引起了国际大型凝血诊断公司 Diagnostica Stago 的兴趣。 公共健康相关性：该提案旨在开发一种快速、高通量的临床检测方法，用于检测 3' 纤维蛋白原，这是一种新出现的静脉血栓栓塞危险因素。该测定将被医生用于静脉血栓栓塞的风险评估，并将指导他们的临床管理，特别是他们对患者抗凝治疗的使用。使用该测定获得的信息将识别出有深静脉血栓形成风险且应接受抗凝治疗的患者，反之，将识别出静脉血栓栓塞风险较低且不应接受抗凝治疗的患者。