Early Detection Resrearch Network - Biomarker Reference Laboratory

任务1：癌症生物标志物的验证，生物标志物测定的分析验证，以及生物标志物测定的开发。在IAA期间，EDRN研究人员开发的癌症生物标志物和/或检测方法将需要NIST的BRL进行验证。在与EDRN指导委员会协商后，NCI签约官员技术代表将向NIST提供待执行工作的书面说明。然后NIST将提供一份实验计划，其中包括测定方法、样本/标本来源、评价标准、参与人员、拟议里程碑和估计成本。拟定方案必须为NCI、NIST和（如适用）发起EDRN研究者所接受。NIST对这些项目的接受取决于NIST工作人员的可用性、他们的专业知识、设施和IAA提供的资金。预计NIST将首先承担任务2中描述的三个项目。在本IAA期间，NCI签约官员技术代表可向NIST BRL分配优先级高于任务2所述项目的其他项目。这可能需要NIST从任务2中描述的项目中重新分配人员。任务二：生物标志物和检测开发项目a）尿液作为癌症生物标志物的非侵入性生物液体FDA应开发方法，以分离和定量测量非泌尿道癌症尿液中的DNA癌症生物标志物，和/或验证泌尿道或非泌尿道癌症尿液中的特定DNA生物标志物。B）单个循环肿瘤细胞（CTC）的捕获和分子分析管理局应使用微流控平台从全血中分离CTC，使用先进的成像技术获得表型信息，测量单个捕获CTC的microRNA和蛋白质释放，测量细胞裂解后的单细胞转录组和蛋白质含量，联合收割机将来自成像和分子分析的信息结合起来，以产生来自细胞的标记，并将细胞标记与疾病类型相关联。c）microRNA测量管理局应使用基于多动物滴定的实验设计确定microRNA测定的性能（平台内和平台间），以评估技术性能，确定变异来源，并比较实验室和平台间的结果。未来可能的项目可能包括但不限于用于癌症检测的纳米技术，DNA损伤/病变作为癌症风险评估和早期检测的生物标志物，以及癌症干细胞的成像计量学任务3：为NCI签约官员技术代表提供支持，以准备部分或全部来自协议下执行的工作的相关手稿。支持应包括所有应用的分析程序的技术说明和参考。任务4：为其他EDRN研究人员提供有关检测标准化、优化和质量控制的指导。任务5：管理由NCI签约官员技术代表批准的个人方案或研究与合作项目。任务六：验证参与研究中心是否按照要求将所有相关的人类风险保证文件存档于NIH风险防护办公室（OPRR）。私人执业医生必须在中心存档经批准的非机构研究者协议（NIA）。任务七：确保所有涉及人体标本的项目均得到NIST IRB的批准，材料转移协议得到NIST官员的批准。任务八：根据奖励的条款和条件，对NIST官员和NCI负责，确保IAA支持的研究的绩效和适当开展。任务九：担任指导委员会的无表决权成员，参加规划讲习班和专题讨论会，每年有两名高级工作人员参加两次指导委员会会议和一次EDRN讲习班或专题讨论会。任务十：与NCI合作，以确保NCI与NIST共同拥有本奖项下开发的数据的权利，并且NCI和NIST可以自由使用数据，但须遵守与现行NIST、HHS、PHS和NIH政策一致的政府访问权。任务十一：执行网络合作研究指导委员会商定的目标、优先事项、共同协议、程序和政策。任务十二：确保EDRN和NCI审查和批准方案、概念、最终方案文件、知情同意书和研究修订案，并告知NCI方案状态的变更。任务十三：就共同的研究设计或协议进行合作，包括指导委员会建议的联合参与和合作的方法和要求，以及数据处理，包括在合作组织之间适当分享方法和数据，并提出相互之间、与网络其他组成部分以及与国家癌症研究所的沟通战略。任务14：调整数据管理系统，使其与EDRN数据基础设施兼容。

Task 1: Validation of cancer biomarkers, analytical validation of biomarker assays, and development of biomarker assays. During the term of this IAA, cancer biomarkers and/or assay methods developed by EDRN investigators will need validation by the BRL at NIST. The NCI Contracting Officer Technical Representative, after consultation with the EDRN Steering Committee, will provide NIST with a written description of the work to be performed. NIST will then provide an experimental plan that includes assay methods, source of samples/specimens, evaluation criteria, staff involved, proposed milestones, and estimated costs. The proposed protocols must be acceptable to NCI, NIST and, if applicable, the initiating EDRN investigator. The acceptance of these projects by NIST is contingent upon availability of NIST staff, their expertise, facilities, and funds provided by this IAA. It is anticipated that NIST will initially undertake the three projects described in Tasks 2. During the term of this IAA, the NCI Contracting Officer Technical Representative may assign other projects to the NIST BRL that are of higher priority than those described in Task 2. This may require NIST to reassign staff from the projects described in Task 2. Task 2: Biomarker and assay developmental projects a) Urine as the noninvasive biological fluid for cancer biomarker The Agency shall develop methods to isolate and quantitatively measure of DNA cancer biomarkers in urine for non-urinary track cancers and/or validate specific DNA biomarkers in urine for either a urinary or non-urinary track cancers. b) Capture and molecular analysis of single circulating tumor cells (CTCs) The Agency shall use a microfluidic platform to isolate CTCs from whole blood, obtain phenotypic information using advanced imaging techniques, measure microRNA and protein release from single captured CTCs, measure single cell transcriptome and protein content following cell lysis, combine information from imaging and molecular analysis to produce signature from the cell and correlate cell signatures with disease type. c) MicroRNA measurements The Agency shall determine the performance of microRNA assays (within platform, and amongst platforms), using a multiple-animal titration-based experiment design, to assess technical performance, identify sources of variation, and compare results across labs and platforms. Future possible projects may include but are not limited to nanotechnologies for cancer detection, DNA damage/lesions as biomarkers for cancer risk assessment and early detection, and imaging metrology for cancer stem cells Task 3: Provide support to the NCI Contracting Officer Technical Representative in preparing programmatic relevant manuscripts for publication that derive in part or entirely from work performed under the agreement. The support shall include technical descriptions of and references for all the applied assay procedures. Task 4: Provide guidance to other EDRN investigators regarding assays standardization, optimization, and quality control. Task 5: Manage individual protocols or research and collaborative projects approved by the NCI Contracting Officer Technical Representative. Task 6: Verify that participating sites have all relevant human risk assurance documents, as required, on file with the Office for Protection from Risk (OPRR), NIH. Physicians in private practice must have an approved Non-institutional Investigator Agreement (NIA) on file with the Center. Task 7: Ensure that all projects involving human specimens are approved by the NIST IRB and that Material Transfer Agreements are approved by NIST officials. Task 8: Assume responsibility and accountability to NIST officials and to the NCI for the performance and proper conduct of the research supported by the IAA in accordance with the terms and conditions of the award. Task 9: Serve as a nonvoting member of the Steering Committee, participate in planning workshops and symposia, and have two senior staff members attend two Steering Committee meetings and one EDRN workshop or symposia per year. Task 10: Collaborate with NCI to ensure that NCI is a joint-owner with NIST of rights to the data developed under this award, and that NCI and NIST may freely use the data, subject to Government rights of access consistent with current NIST, HHS, PHS, and NIH policies. Task 11: Implement the goals, priorities, common protocols, procedures, and policies agreed upon by the Steering Committee for the Network collaborative studies. Task 12: Ensure EDRN and NCI review and approval of protocol, concepts, final protocol documents, informed consents, and study amendments, and advise NCI of changes in protocol status. Task 13: Collaborate on common research designs or protocols, including methods and requirements for joint participation and collaboration as recommended by the Steering Committee, and handling of data, including appropriate sharing of methods and data among collaborating organizations, and propose strategies for communication among themselves, with the other Network components, and with the NCI. Task 14: Adapt data management system so that it is compatible with EDRN data infrastructures.