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）：该申请的长期目标是为3'纤维蛋白原开发快速，高通量的临床测定法，该测定将用于评估患者发展静脉血栓栓塞的风险。该测定法将指导临床管理，特别是对患者使用长期抗凝治疗。该测定法的实用性将是确定应抗原静脉血栓栓塞风险的患者，相反，鉴定出患有静脉血栓栓塞风险较低的患者，这些患者不应受到抗凝治疗的可能危险。该快速应用程序I期的特定目的是：1）为3'纤维蛋白原开发快速，高通量测定法。这将使用我们的专有单克隆抗体2.G2.H9和Luminex XMAP（R）技术平台来完成。成功完成I期和向II期的过渡的里程碑是开发3'纤维蛋白原测定法，该测定法的血浆中3'纤维蛋白原的正常范围从0-1.5 mg/mL，并以> 0.95的R2精度达到标准曲线拟合。在II期中，具体目的是：2）验证3'纤维蛋白原测定法。该测定法将使用临床和实验室标准研究所（CLSI）发表的指南，评估线性，干扰测试，方法比较，偏置估计以及与先前基于板的ELISA的比较，以精确执行定量测量方法。该信息对于食品药物管理局（FDA）和临床实验室改进修订（CLIA）评估将是必不可少的； 3）定量随时间推移的三'纤维蛋白原水平的个体内变异性。这将通过在一年一年的时间内和每月时间点在每周时间点测量个体的3'纤维蛋白原水平来实现，以确定受试者内部的可变性。这些信息对于广泛接受临床实验室的测定至关重要； 4）扩大测定套件组件的生产。这将在OHSU技术转移与业务开发办公室的协助下完成，该办公室与企业家和本地商业社区建立了联系，为利用OHSU研究的公司的发展提供了支持框架。他们的跳板计划旨在促进基于OHSU技术的新企业的发展。我们已经吸引了主要的国际凝血诊断公司Diagnostica Stago的兴趣。 公共卫生相关性：该建议是为3'纤维蛋白原（静脉血栓栓塞新出现的危险因素）开发快速，高通量的临床测定法。该测定法医生将用于静脉血栓栓塞的风险评估，并将指导其临床管理，尤其是他们在患者中使用抗凝治疗。从使用此测定中获得的信息将确定应抗凝静脉血栓形成风险的患者，相反，将确定不应接受抗凝治疗的静脉血栓栓塞风险较低的患者。