National Immunohistochemistry Standardization Program - Establishment & Launch

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。IHC是唯一没有参考文献的临床实验室学科 标准和可追溯的计量单位。这是尽管事实上IHC是一个主要的测试格式， 外科病理学;典型的医院IHC实验室具有大约200种不同测试的测试菜单。作为 结果，IHC分析错误率范围为10 - 30%，而其他类型的临床诊断错误率<1%。 实验室测试这些错误影响预测性标志物（HER 2、PD-L1）以及诊断性标志物。 标记（例如，TTF-1，第53页）。从20世纪50年代到70年代，临床化学领域广泛 采用这些更高的实践标准，错误率直线下降。该项目的目的是 在临床IHC中证明了相同的益处。 该申请人在克服了一个重要的技术障碍后具有独特的资格。波士顿细胞 标准开发了第一个IHC校准品，其分析物浓度可追溯到公认的 标准- NIST标准参考物质1934。该项目的两个具体目标是：（1） 确定准确的临床IHC检测的定量校准范围，以及（2）测量 校准品有助于报告准确的测试结果。这将是第一个研究 分析灵敏度与诊断灵敏度和特异性。也就是说，每个细胞有多少个分子（ 目标分析物）必须能够检测 测试结果？这对于报告为阳性/阴性的定性测试也很重要， 在IHC中常见。这种分析虽然在其他实验室检测领域很常见，但对IHC来说是新的。的 实验研究设计使用包括组织微阵列的临床IHC实验室调查工具 (TMA)和IHC校准品。TMA生成诊断灵敏度和特异性数据， 校准器产生分析灵敏度数据。 该项目发起了一个新的联盟，包括波士顿细胞标准，国际IHC 能力验证机构和学术界。尽管在创造高影响力方面有先例 对于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。 目标是建立和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，以将参考标准品整合到IHC中。联营集团成员 是实验设计、执行和数据解释的积极合作伙伴。拟定临床试验 该格式已与一些合作伙伴成功地进行了测试并公布。

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.