National Immunohistochemistry Standardization Program - Establishment & Launch

国家免疫组织化学标准化计划-建立

• 批准号: 10383397
• 负责人: Steven A Bogen
• 金额: $ 110.14万
• 依托单位: BOSTON CELL STANDARDS INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383397
• 关键词: Academia; Address; Adopted; Adoption; Affect; Biological Assay; Biopsy; Boston; Calibration; Cells; Clinical; Clinical Chemistry; Clinical Chemistry Tests; Clinical Trials; Data; Data Analyses; Diagnostic Sensitivity; Discipline; ERBB2 gene; Europe; Evaluation; Experimental Designs; Funding; Future; Goals; Hospitals; Immunohistochemistry; International; Investigation; Journals; Laboratories; Learning; Legal patent; Measurement; Measures; Medical; Microscope; Modeling; North America; Output; Patients; Performance; Pilot Projects; Problem Solving; Publishing; R44 grant; ROC Curve; Reference Standards; Reporting; Research Design; Sampling; Sensitivity and Specificity; Slide; Small Business Innovation Research Grant; Stains; Standardization; Surgical Pathology; Surveys; TP53 gene; Technology; Test Result; Testing; Tissue Microarray; Tissues; Unit of Measure; accurate diagnostics; analytical tool; cancer biomarkers; detection limit; diagnostic accuracy; diagnostic biomarker; editorial; experimental study; follow-up; high standard; member; novel; predictive marker; programmed cell death ligand 1; programs; rat Ran 2 protein; standard of care; tool

The overarching goal of this project is to change laboratory practice in the Clinical Immunohistochemistry (IHC) laboratory. IHC is the only clinical laboratory discipline without reference standards and traceable units of measure. This is despite the fact IHC is a major testing format in surgical pathology; a typical hospital IHC lab has a test menu of approximately 200 different tests. As a result, IHC analytic error rates range from 10 – 30% as compared to <1% for other types of clinical laboratory testing. These errors affect both predictive markers (HER2, PD-L1) as well as diagnostic markers (e.g., TTF-1, p53). From the 1950's to the 1970's, the field of Clinical Chemistry broadly adopted these higher standards of practice and error rates plummeted. This project is for the purpose of demonstrating the same benefit in Clinical IHC. This Applicant is uniquely qualified after having surmounted an important technical hurdle. Boston Cell Standards developed the first IHC calibrators with analyte concentrations traceable to a recognized standard - NIST Standard Reference Material 1934. The two Specific Aims of this project are: (1) Identify quantitative calibration ranges for accurate Clinical IHC testing, and (2) measure the benefit that calibrators offer towards reporting accurate test results. These will be the first studies correlating analytic sensitivity with diagnostic sensitivity and specificity. Namely, how many molecules per cell (of the target analyte) must the assay be capable of detecting in order to produce a diagnostically accurate test result? This is important even for qualitative tests that are reported as positive/negative, which are common in IHC. This analysis, while common in other fields of laboratory testing, is new to IHC. The experimental study design uses a Clinical IHC laboratory survey tool comprising a tissue microarray (TMA) and IHC calibrators. The TMA generates diagnostic sensitivity and specificity data while calibrators generate analytic sensitivity data. This project initiates a novel consortium that includes Boston Cell Standards, international IHC proficiency testing agencies, and academia. Although there is precedent in creating high-impact standardization programs for Clinical Chemistry testing, such an organization is unprecedented for IHC. The goal is to create and launch a National Immunohistochemistry Standardization Program, to oversee and execute data-driven studies for integrating reference standards to IHC. The consortium members are active partners in experimental design, execution, and data interpretation. The proposed clinical trial format has already been successfully tested and published with some of the consortium partners.

该项目的总体目标是改变临床实验室实践 免疫组织化学（IHC）实验室是唯一没有参考文献的临床实验室学科。 尽管 IHC 是主要的测试格式，但仍存在这种情况。 外科病理学；典型的医院 IHC 实验室有大约 200 种不同测试的测试菜单。 结果，IHC 分析错误率范围为 10 – 30%，而其他类型的临床分析错误率 <1% 这些错误会影响预测标记（HER2、PD-L1）和诊断。 标记物（例如 TTF-1、p53）从 20 世纪 50 年代到 1970 年代，广泛应用于临床化学领域。 采用这些更高的实践标准和错误率大幅下降是本项目的目的。 在临床 IHC 中证明了相同的益处。 该申请人在克服了波士顿细胞的重要技术障碍后具有独特的资格。 Standards 开发了第一款 IHC 校准品，其分析物浓度可追溯到公认的标准 标准 - NIST 标准参考材料 1934。该项目的两个具体目标是：(1) 确定准确的临床 IHC 测试的定量校准范围，以及 (2) 衡量以下益处： 校准器可以报告准确的测试结果，这将是第一个相关研究。 分析灵敏度与诊断灵敏度和特异性，即每个细胞有多少分子。 目标分析物）测定必须能够检测才能产生诊断准确的结果 即使对于报告为阳性/阴性的定性测试，这也很重要，这些测试结果是 这种分析在其他实验室检测领域很常见，但对于 IHC 来说是新的。 实验研究设计使用包含组织微阵列的临床 IHC 实验室调查工具 (TMA) 和 IHC 校准品同时生成诊断灵敏度和特异性数据。 校准器生成分析灵敏度数据。 该项目发起了一个新颖的联盟，其中包括 Boston Cell Standards、国际 IHC 尽管能力验证机构和学术界有过创造高影响力的先例。 临床化学测试的标准化计划，这样的组织对于 IHC 来说是前所未有的。 目标是创建并启动国家免疫组织化学标准化计划，以监督 并执行数据驱动的研究，将参考标准整合到联盟成员中。 是实验设计、执行和数据解释方面的积极合作伙伴。 该格式已与一些联盟合作伙伴成功测试并发布。