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.
