EXPIRED
National Institutes of Health (NIH)
U2C Resource-Related Research Multi-Component Projects and Centers Cooperative Agreements
The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for Biomarker Characterization Centers (BCCs), one of the three scientific units of the Early Detection Research Network (EDRN). The EDRN is a national infrastructure to discover, develop, and validate biomarkers and imaging methods for early cancer detection and risk assessment. BCCs will (1) discover, develop, characterize and test new biomarkers or refine existing biomarkers, (2) develop, refine and/or standardize biomarker assays, (3) provide resources and support for the validation of biomarkers developed by the EDRN, and (4) participate in collaborative projects with other laboratories and centers.
The other two scientific units of the continuing EDRN program are the Clinical Validation Centers (CVCs), which will conduct clinical research on the validation of biomarkers and will serve as resource centers for the Network by participating in collaborative biomarker validation studies with EDRN BCCs; and the Data Management and Coordinating Center (DMCC), which will support statistical and computational analyses, informatics infrastructure, study design, coordination and management of EDRN-sponsored biomarker validation studies, and the coordination of Network-wide meetings and workshops.
30 days prior to the application due date.
Application Due Dates | Review and Award Cycles | ||||
---|---|---|---|---|---|
New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
September 08, 2022 | September 08, 2022 | Not Applicable | November 2022 | January 2023 | April 2023 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
No late applications will be accepted for this Funding Opportunity Announcement.
Not Applicable
It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
The purpose of this FOA is to solicit applications for Biomarker Characterization Centers (BCCs); a scientific unit of the Early Detection Research Network (EDRN). EDRN (http://edrn.nci.nih.gov/) is an integrated infrastructure to develop and validate biomarkers and imaging methods for the detection of early-stage cancers and risk assessment. The other two scientific units of the EDRN are Clinical Validation Centers (CVCs) and a Data Management and Coordinating Center (DMCC).
Each BCC will have two main functional components (1) a Biomarker Developmental Laboratory (BDL), which will discover, develop, characterize and test new biomarkers or refine existing biomarkers, and (2) a Biomarker Reference Laboratory (BRL), which will (i) develop, refine and/or standardize biomarker assays and (ii) provide resources and support for the validation of biomarkers developed by the EDRN. Both components will participate in collaborative projects with other laboratories and centers.
CVCs (RFA-CA-22-039; U01) will conduct research to validate biomarkers and imaging methods for risk assessment and detection of early-stage cancers. CVCs will also serve as resource centers for collaborative research within the EDRN by partnering with BCCs to provide high-quality specimens for biomarker refinement studies as well as collaborating with other CVCs, BCCs, and the DMCC for conducting Network collaborative biomarker validation studies. The CVCs must also have the expertise and ability to conduct clinical utility trials of validated early detection biomarkers and/or imaging methods.
DMCC (RFA-CA-21-034; U24) will support the coordination and management of EDRN-sponsored biomarker and/or imaging validation studies, provide statistical and computational analyses, support data science with an informatics infrastructure and repository, assist with study design of collaborative projects, manage Core Funds, and coordinate Network-wide meetings and workshops.
Biomarker Definition. In the context of this FOA, biomarkers are defined as cellular, biochemical, and/or molecular (including genetic and epigenetic) characteristics by which normal and/or abnormal biological processes can be recognized and/or monitored. Biomarkers are measurable in biological materials, such as in tissues, cells, and/or bodily fluids.
Background
The mission of the EDRN is to discover, develop, and validate biomarkers and imaging methods to detect early-stage cancers and precancers that are likely to progress and to translate these into clinical tests. EDRN is a highly collaborative program that helps coordinate biomarker research within the extramural community and with other NCI programs in cancer prevention, screening, and treatment to reduce cancer incidence, morbidity and mortality (see EDRN Strategic Plan available at https://edrn.nci.nih.gov/about/bookshelf). Since its inception in 2000, the EDRN has followed a "vertical" approach to develop and validate early detection biomarkers that rely on collaborations and hand-offs among technology developers, basic scientists, clinicians, radiologists, epidemiologists, biostatisticians, and other health professionals.
The NCI expects that EDRN investigators will collaborate with industry, both to develop biomarkers and/or reagents and to provide a clinical environment for the evaluation of new technologies. Early interactions with industry-leading to research collaborations are likely to benefit both EDRN investigators and industry partners. Many EDRN investigators have had fruitful collaborations with the industry in the past. It is hoped that validated biomarkers and/or imaging methods will ultimately be commercialized into diagnostic products for early detection of cancer and cancer risk assessment and subsequently be tested in clinical utility trials.
The EDRN provides an infrastructure to expedite the clinical application of molecular and imaging data through its knowledge environment, which was developed in collaboration with NASA's Jet Propulsion Laboratory (JPL). The architecture of the knowledge environment is based on supporting and linking diverse molecular data (genomics, proteomics, etc.) to clinical phenotypes and imaging. The EDRN Informatics Center at JPL (JPL IC) leverages cloud-based capabilities to support the increasing data and computational demands of the program. The infrastructure also supports capabilities to run repeat analyses of complex genomics and proteomics data, image analysis including radiomics, and other complex data types. Over the years, EDRN has built several data repositories on biomarkers, imaging, and analytical tools. These resources will be employed to help build specific, interoperable data platforms that will allow investigators to mine and analyze data using artificial intelligence (AI) and other machine learning languages (MLL). Data science is poised to play a major role in new or improved risk stratification, early detection, and precision prevention strategies, particularly in patients with ambiguous symptoms or at high risk for the disease. In recent years, EDRN has amassed large amounts of imaging data and combined it with clinical information to diagnose patients, recognize tumor types, and/or make any follow-up care and treatment decisions. These imaging and data analytics will provide unprecedented opportunities for in silico biomarker discovery, accurately identify early-stage aggressive neoplasms from indolent or benign lesions for many cancers and make more accurate predictions about their aggressiveness.
EDRN's specific interests include but are not limited to the following:
These goals are achieved through a systematic, evidence-based discovery, development, and validation of biomarkers, based upon standard operating procedures (SOPs) and common data elements (CDEs) developed by the EDRN investigators, as well as Network scientific, operational, and organizational policies and procedures, as described in the EDRN Manual of Operations (MOP) (https://edrn.nci.nih.gov/about/bookshelf). The EDRN has established a five-phase biomarker development framework as a standard and a roadmap for successfully translating research on biomarkers from the laboratory to the bedside. The five phases for biomarker discovery and validation are:
The EDRN has also proposed a coherent and comprehensive set of guidelines for biomarker discovery and validation studies for early cancer detection, diagnosis, and prognosis, known as the prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) study design (see link below). The PRoBE study design includes four key units, which relate to 1) the clinical context and outcomes; 2) criteria for measuring biomarker performance; 3) the biomarker itself, and 4) the sample size included in the study. The PRoBE study design involves prospectively collected biological specimens from a cohort that represents the target population envisioned for clinical application of the biomarker. Nested case-control studies, as described in the PRoBE study design, can improve the quality of discovery research and increase the chances of truly valuable markers to undergo definitive evaluation. The biomarker is assayed in a blinded fashion on the specimens collected prior to and near the time of diagnosis among the case subjects and at similar times in the control subjects in the cohort. Studies using such banked specimens and data collected prior to symptoms or diagnosis are increasingly recognized as precious resources for making comparisons that have strong internal validity. Clinical studies seldom have prediagnostic specimens on most subjects because obtaining them requires following large cohorts of asymptomatic people, ideally at periodic intervals, to ascertain if they develop cancer. One biological explanation as to why prediagnostic and clinical early-stage specimens may differ is that acute phase plasma proteins and other molecules may be increased by inflammatory and other conditions present near the time of symptomatic diagnosis.
The articles on the five-phase approach and PRoBE study design are available on the EDRN website (https://edrn.nci.nih.gov/about/bookshelf).
EDRN Administrative and Governance Structure (For Information Only)
EDRN will be structured around the three main scientific units - BCCs, CVCs, and DMCC. Although individual teams of EDRN awardees for the BCCs, CVCs, and DMCC will operate independently, they will be required to interact closely with other EDRN awardees and engage in collaborative activities with them.
The current EDRN administrative structure is composed of the following:
Steering Committee: The Steering Committee, which includes representatives of the EDRN awardees and the NCI, is the governing body of EDRN that integrates the efforts of all EDRN awardees and provides oversight of collaborative activities. The Chair and co-Chair of the Steering Committee are PDs/PIs of EDRN cooperative agreement awards and are elected by the Steering Committee. Any member of the Steering Committee can offer nominations for the Chair and co-Chair. The co-Chair serves as the Chair of a small subgroup of the Steering Committee, the Executive Committee. Other members of the Executive Committee include the leading PD/PI of the DMCC, a PD/PI or MPI from BCCs who are involved in assay development, the NCI Project Coordinator, and the Chairs of the EDRN Collaborative Groups. (EDRN Collaborative Groups are based on organ sites and EDRN PDs/PIs can be members of one or more Collaborative Groups.)
Further details of Steering Committee composition and responsibilities are provided in Section VI.2. Administrative and National Policy Requirements: Cooperative Agreement Terms and Conditions.
Core Fund: The EDRN will have a restricted Core Fund that will be made available to support post-award collaborative research projects, validation of new biomarkers, expansion of the EDRN portfolio, and make the Network inclusive by supporting non-EDRN investigators. Since the Core Fund is restricted and reserved for post-award activities, no requests for Core Fund support can be made in the application in response to this FOA.
The management of the EDRN Core Fund will be the responsibility of the DMCC and will be restricted via a term of the award pending evaluation of proposed projects by the EDRN Steering Committee and NCI approval of the projects. The solicitation of requests for use of Core Fund and the organization of their review will be the responsibility of the Steering Committee. The procedure for selecting activities and releasing the funds will involve the following steps: EDRN-affiliated investigators as well as non-EDRN investigators will be able to request Core Fund support for specific collaborative activities relevant to the EDRN goals. The Steering Committee will assign these requests for review to PDs/PIs from appropriate EDRN Collaborative Groups with the assistance of external reviewers as needed. The final review and selection of requests to be recommended for funding will be conducted by the EDRN Executive Committee. Following these recommendations and the NCI approval of funds release, the DMCC will disburse the approved funds under appropriate subaward agreements.
Network Consulting Team: The Network Consulting Team (NCT) provides independent oversight of research directions and progress of EDRN and is composed of experts in oncology who are not EDRN members and who do not receive funding from EDRN. They are drawn from the extramural community, the FDA, and the private sector. The NCT evaluates EDRN to ensure that the Network is responsive to promising scientific, technological, and collaborative opportunities, by exhibiting flexibility in its structure, composition, and decision-making process, and prioritizing decisions free from conflicts of interest. The NCT meets biannually.
Specific Research Objectives and Requirements
Scope: This FOA encourages the submission of applications to establish the EDRN BCCs. Prior affiliation with the EDRN is not required and all qualified investigators are invited to apply.
The functions of the BCCs include:
Examples of specific research areas include but are not limited to:
Required Capabilities of the BCC
Each BCC will consist of a multidisciplinary, collaborative team with the expertise required to discover and develop biomarkers as well as capabilities to develop clinical-grade biomarker assays. It is desirable that expertise should include, but is not limited to:
Structure of the BCC
Each BCC will consist of an Administrative Core and two highly integrated functional components, a BDL, and a BRL. A brief description of each is provided below, and more application-related details are provided in Section IV. Application and Submission Information of this FOA.
Administrative Core
The Administrative Core will be led by the contact PD/PI of the BCC. Multi-PD/PI and multi-institution applications are encouraged because of the distinct yet integrated nature of the BDL and BRL projects. The primary role is to ensure integrated operations of the BDL and BRL components. The Admin Core will also work with the EDRN DMCC to provide logistical and organizational support. It will ensure that the overall BCC conforms with the agreed practices and principles of the EDRN SOPs, CDEs, and data sharing plan as approved by the EDRN Steering Committee post-award and/or outlined in the EDRN MOP. The Administrative Core will also ensure bidirectional exchange of findings and insights with other BCCs and CVCs, provide resources and support for the validation of biomarkers developed by the EDRN, and ensure participation in collaborative projects with other laboratories and centers.
Biomarker Developmental Laboratory (BDL)
The primary responsibility is to discover, develop, characterize and test new biomarkers or refine existing biomarker-based diagnostic or early detection tests. The approach may include one or more broad discovery platforms or data mining or in silico approaches to support and/or complement discovery efforts. Within EDRN, BDLs will be the primary source of new biomarkers or panels of biomarkers on which validation studies will be conducted. BDLs may also develop new technologies to detect candidate biomarkers, integrate them with imaging methods, and work collaboratively with other laboratories to combine biomarkers to improve the test performance. Integration of multiple discovery platforms, use of modern tools and technologies, as well as data science and MLL algorithms are encouraged. The platforms need to be amenable to clinical use and supported through CLIA regulations.
Biomarker Reference Laboratory (BRL)
The primary responsibility is to develop, refine and/or standardize biomarker assays, either for the BCC it is part of or for other EDRN BCCs and/or CVCs. For early detection screening tests, it is crucial to develop appropriate high-throughput assays/technologies that are accurate, reproducible, and cost-effective. The BRL will provide resources and support for analytical and clinical validation of biomarker assays, including testing of candidate biomarkers, development of assays and/or their refinement, and standardization of assay methods as requested by the EDRN Steering Committee. When appropriate, BRLs must follow the principles described in the PRoBE (or a similar) study design. In addition to general sound laboratory practices, BRLs must adhere to the theory and principles of CLIA or CAP laboratories that are compliant with GLP or GMP practices. The main functions of a BRL component are: (1) methodology/protocol development; (2) assay design; (3) assay optimization; (4) assay validation and clinical application development; and (5) quality control program.
Types of Cancer: Applications on cancers of the breast, and other lethal cancers, e.g., sarcoma, stomach, melanoma, bladder, endometrial, etc. are encouraged. Currently, EDRN has a representation of BCCs for cancers of the prostate, lung, colon, and ovary based on response to the previous BCC FOA (RFA-CA-21-035). In addition, discovery of biomarkers for pancreatic cancer and liver cancer is conducted separately through the Pancreatic Cancer Detection Consortium (https://prevention.cancer.gov/major-programs/pancreatic-cancer-detection-consortium) and the Translational Liver Cancer Consortium (https://prevention.cancer.gov/major-programs/translational-liver-cancer-consortium), respectively. Applications focused on these cancer types will be considered of a lower priority to this FOA. Focus on individual tests for more than one cancer type or on one test for simultaneous detection of multiple cancers is acceptable.
Non-responsive Applications
This FOA will not support research on new genome-wide association studies (GWAS), mechanistic studies, such as studies on growth regulation, cell cycle control, or other basic studies, which are not explicitly focused on risk assessment, on early cancer detection, and on molecular diagnosis and prognosis of early cancers in humans. Applications using convenience samples (i.e., samples to be used were not collected based on SOPs and/or the intended clinical use of the biomarkers to be developed and not in compliance with the PRoBE or a similar study design for minimizing bias) will also be considered non-responsive. Non-responsive applications will not proceed to review.
Note: NCI will hold a pre-application informational webinar for this FOA. When published, the related Notice will be linked with the FOA and webinar details will also be posted on the EDRN website (http://edrn.nci.nih.gov/).
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
Resubmission of applications submitted in response to RFA-CA-21-035
Not Allowed: Only accepting applications that do not propose clinical trials.
NCI intends to commit $4.1 million in FY 2023 and $6 million per year in FY 2024-2027 to fund up to 6 awards.
A budget of up to $500,000 per year (direct cost) may be requested for Year 1 (FY 2023), and a budget of up to $725,000 per year (direct cost) may be requested for Years 2-5 (FY 2024-2027).
Application budgets must reflect the actual needs of the proposed project.
The total project period may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
Given the multi-component nature of the EDRN BCC and the multidisciplinary expertise required for an exemplary response to the BCC objectives, this FOA encourages the use of the multi-PD/PI option.
An investigator designated as a Contact PD/PI of an application under this FOA must not be the designated Contact PD/PI of another application under this initiative or under the companion FOA (RFA-CA-22-039). The Contact PD/PI can be an MPI or Co-I on another application, whether for this FOA or its companion FOA. An MPI on a BCC application may be an MPI or a Co-I on another application, whether in response to this FOA or the companion FOA.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Sudhir Srivastava, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7028
Email: srivasts@mail.nih.gov
Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Component | Component Type for Submission | Page Limit | Required/Optional | Minimum | Maximum |
---|---|---|---|---|---|
Overall | Overall | 12 | Required | 1 | 1 |
Admin Core | Admin Core | 6 | Required | 1 | 1 |
Core - Biomarker Developmental Laboratory (BDL) | Biomarker Dev Lab | 12 | Required | 1 | 1 |
Core - Biomarker Reference Laboratory (BRL) | Biomarker Ref Lab | 12 | Required | 1 | 1 |
Instructions for the Submission of Multi-Component Applications
The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.
The application should consist of the following components:
Overall Component
When preparing your application, use Component Type Overall .
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424(R&R) Cover (Overall)
Complete entire form.
PHS 398 Cover Page Supplement (Overall)
Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.
Research & Related Other Project Information (Overall)
Follow standard instructions.
Project Summary /Abstract: Succinctly describe the types of biomarkers proposed and the tumor type(s) selected for the study to be conducted by the BCC. State briefly how the research will address a clinically unmet need and enhance public health.
Project Narrative: Describe the biomarker characterization project that must encompass a strong focus on discovery followed by clinical-grade assay development.
Facilities & Other Resources: In addition to the information required in the standard instructions, highlight available facilities and/or services that can be leveraged for the biomarker discovery and development (e.g., well-annotated existing cohorts, experimental and/or computational platforms etc.).
In addition, applicants must describe the following:
Other Attachments: Applicants should provide additional supporting materials relevant to the research for which funding from this FOA is sought in the categories defined below. Upload these materials as individual pdf files using the indicated file names (these file names will become bookmarks in the application).
Project/Performance Site Locations (Overall)
Enter primary site only.
A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.
Research and Related Senior/Key Person Profile (Overall)
Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.
In addition, the following specific requirements must be addressed:
A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.
Budget (Overall)
The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.
A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.
PHS 398 Research Plan (Overall)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.
Introduction to Application:For Resubmission applications, an Introduction to Application is required in the Overall component.
Specific Aims: Outline the scope, overall vision, and goals for the proposed EDRN BCC for the funding period. Include a statement on the intended use/indication of the proposed product (e.g. diagnostic assay) and the public health gap the product is intended to fill. The goals must be overarching, a high-level view, and be distinct from the aims of the individual components, i.e., the BDL and BRL components.
Research Strategy: In lieu of the standard Research Strategy sub-sections (e.g., Significance, Innovation, Approach), applicants must use the sub-sections defined below to present a concise overall vision and plan for the proposed BCC.
Sub-section A: Scientific Rationale and BCC Product Development
Sub-section B: BCC Organization and Team Integration
To facilitate biomarker translation into ultimate clinical application, BCC applicants are encouraged to actively seek additional funding/resources to push the biomarkers validation/implementation efforts beyond the EDRN-sponsored scope of research.
Address the following aspects:
Sub-section C: Workflow for the Functional Components
Sub-section D: Previous Accomplishments
Note: The articles on the five-phase approach and PRoBE are available on the EDRN website (https://edrn.nci.nih.gov/about/bookshelf).
Applicant must demonstrate expertise in, although it is not limited to, the following:
Methodologies:
Assay Design:
Assay Optimization:
Assay Validation and Clinical Application Development:
Quality Control Program:
Sub-section E: Health Disparity
Demonstrate access to biospecimens from racial and ethnic minority populations that are representative of the race/ethnic diversity in the United States and/or from other NIH-designated populations that experience health disparities. Address any opportunities that exist and, if implemented, can narrow the gaps in minority health and NIH-designated populations that experience health disparities who continue to suffer disproportionately from certain cancers and have higher cancer incidence. NIH defines health disparity populations as racial and ethnic minority populations, less privileged socioeconomic status (SES) populations, underserved rural populations, sexual and gender minorities (SGM), andany subpopulations that can be characterized by two or more of these descriptions (https://www.nimhd.nih.gov/about/strategic-plan/nih-strategic-plan-definitions-and-parameters.html#:~:text=NIH%20defines%20health%20disparity%20populations,or%20more%20of%20these%20descriptions).
Sub-section F: Project Management Plan
Overall milestones: Describe the timeline for the overall BCC project with brief descriptions of how the goals of each of the proposed specific aims will be achieved annually. Specific aims themselves may not be regarded as milestones (unless they include quantitative endpoints). The overall milestones must be well-described, quantitative, and scientifically justified. Discuss the milestones as a means of judging the success of the proposed project during the 5-year support. In addition, the applicants should clearly delineate the timeline for the transition of biomarkers from Phase 1 to Phase 2, and to Phase 3 validation.
Shortly before the completion of the third year of the award, the progress made towards these milestones will be reviewed by a virtual or in-person site visit of the laboratory by Program staff members and external expert consultants. A decision by NCI will be made at that time based on the comments from the site visit review team as to whether the overall goals of the BCC should be adjusted and/or modified for the remaining period of the 5-year term.
Letters of Support: In addition to standard items, applicants must provide letters from the respective leadership official(s) in the institution(s) of the proposed center documenting specific institutional commitments to the proposed center. Letters should also be included that reflect any additional resources and partnerships (e.g., for-profit sector, industry) that will be employed to achieve the goals of the BCC.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
All applications, regardless of the amount of direct costs requested for any one year, should address a Resource and Data Sharing Plan. The Resource and Data Sharing Plan should be provided only under the Overall component but it should cover all the activities of the BCC.
(a) Specimen and Data Sharing: The success of EDRN is dependent on the collaborative interactions of all its laboratories. Clinical specimen collections funded through EDRN cooperative agreements must become available to all investigators in the Network and must be made available for Network validation studies. Applicants seeking to use funding via this U2C mechanism to collect clinical specimens must state their willingness to share these samples with others in the Network.
(b) Intellectual Property: Collaboration among EDRN investigators, as well as between Network investigators and third-party industry partners is a core mission of the EDRN, which entails the sharing of intellectual property arising out of research resources developed in Network-related activities.
Applicants are expected to submit an Intellectual Property Management Plan (IPMP) in line with the accepted IP Rights and Responsibilities (https://edrn.nci.nih.gov/about/bookshelf). The proposed plan should address the strategy to be followed for both solely or jointly owned inventions (including patents and licensing issues) and how these resources will be made available to the broader scientific community, consistent with the EDRN initiative. Any approved IPMP will become a condition of the award (https://edrn.nci.nih.gov/about/bookshelf).
Note: For EDRN-related public-private partnerships, please visit the EDRN website (http://edrn.nci.nih.gov). Industry scientists or collaborators can provide valuable expertise, reagents, and technology for biomarker discovery. EDRN encourages pharmaceutical and biotechnology companies to participate in Network-sponsored studies for moving biomarkers through qualification for an FDA-approved clinical use. In structuring such partnerships or collaborations, applicants need to consider pre-existing intellectual property rights associated with the use of existing models/reagents and make appropriate licensing arrangements. List and summarize each of the agreements with industry collaborators, including a description of the materials, technologies, and/or expertise to be provided by such collaborators. NCI will serve as a concierge to facilitate partnerships with relevant laboratories and centers within EDRN. If proprietary tools/devices are used in the BCC activities, applicants should clearly state the licensing agreement and are advised to contact NCI and seek assistance as needed from the NCI Technology Transfer Center (https://ttc.nci.nih.gov/) in determining whether such arrangements are appropriate and/or adequate. Detailed documentation of license agreement(s), intellectual property arrangements, and data sharing concerning the proposed or existing collaboration with an industrial partner(s) will be expected as appropriate if an applicant is selected for consideration for funding. The applicant's technology transfer office should be involved in reviewing such documents for the applicant institution prior to submission.
Appendix:
Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Overall)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
PHS Assignment Request Form (Overall)
All instructions in the SF424 (R&R) Application Guide must be followed.
Administrative Core
When preparing your application, use Component Type Admin Core.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (Administrative Core)
Complete only the following fields:
PHS 398 Cover Page Supplement (Administrative Core)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (Administrative Core)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.
Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (Administrative Core)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachments for additional entries.
Research & Related Senior/Key Person Profile (Administrative Core)
Budget (Administrative Core)
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (Administrative Core)
Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.
Specific Aims: Outline specific aims for the Administrative Core.
Research Strategy: In lieu of the standard Research Strategy subsections (e.g., Significance, Innovation, Approach), use the sub-sections defined below to explain how the effective administrative and organizational capabilities of the Administrative Core will:
Applicants must also review Section I. Funding Opportunity Description for expectations from the Administrative Core.
Sub-section A. BCC Leadership and Admin Core Organization
Address the major responsibilities of the Administrative Core that are listed above. Outline the organization of the leadership structure and overall BCC structure (provide respective organizational diagrams). Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating institutions (i.e., institution submitting application and participating institutions on a sub-contractual basis).
Sub-section B. Center Logistics and Communication
Describe the strategies for communication between:
State who will be the lead for each level of communication.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Resource Sharing Plans should only be included in the Overall component, as instructed before.
Appendix:
Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.
PHS Human Subjects and Clinical Trials Information (Administrative Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
Biomarker Developmental Laboratory (BDL)
When preparing your application, use Component Type Core - Biomarker Developmental Laboratory (BDL)
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (BDL)
Complete only the following fields:
PHS 398 Cover Page Supplement (BDL)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (BDL)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations?
Vertebrate Animals: Answer only the Are Vertebrate Animals Used?
Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (Administrative Core)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachments for additional entries.
Project /Performance Site Location(s) (BDL)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachments for additional entries.
Research & Related Senior/Key Person Profile (BDL)
Budget (BDL)
Budget forms appropriate for the specific component will be included in the application package.
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (BDL)
Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.
Specific Aims: Outline specific aims for the BDL and provide a rationale and description of how each aim addresses a specific aspect of the overall development of new biomarkers to address an unmet clinical need or refinement of existing diagnostic or early detection tests.
Research Strategy: In lieu of the standard Research Strategy subsections (e.g., Significance, Innovation, Approach), use the sub-sections defined below to describe the activities of this functional component.
Applicants must also review Section I. Funding Opportunity Description for expectations from the BDL component.
Sub-section A. Study Rationale
The focus of the proposed translational studies is expected to be on the discovery, development and testing of biomarkers of cancer risk and/or early cancer. The development of diagnostic and/or prognostic markers for early cancers may also be proposed, provided that the selection is sufficiently justified and reflects urgent clinical needs. If proposing biomarker development for more than one organ site within the application, provide specific information for the organ sites in a distinct manner. If proposing simultaneous detection of multiple cancer types, provide justification for the different cancer types included as well as the types of biomarkers to be studied.
Sub-section B: Biospecimen Source and Identification
The applicant is required, if applicable to their proposed research, to address the following in the proposed study:
Sub-section C: Biomarker Development Plan
In the context of this FOA, the development will encompass further studies to evaluate and validate promising candidate biomarkers identified by applicants themselves or by other investigators in accordance with EDRN-defined Phase 2 and Phase 3 biomarker development approaches (described earlier). Integration of multiple discovery platforms, use of modern tools, technologies, digital approaches, in silico approaches, as well as a strong emphasis on data science, AI, and MLL algorithms are encouraged. Other modern technological approaches for the development of biomarkers for early detection, diagnosis, prognosis, or assessment of cancer risk will be accepted as well.
(A) Biomarker Development Approach:
Applicants must describe the study design and approaches to be followed for the proposed BDL studies. Broadly, the approach may include one or more of broad discovery platforms such as genomics, epigenomics, proteomics, metabolomics, etc.; data mining of existing data (e.g., based on DNA, cell-free DNA, gene fusion, RNA, circular RNA, microRNA [miRNA], small and long RNAs, non-coding RNA [ncRNA], mRNA, miRNA, isoforms) or in silico approaches to support/complement discovery efforts; and tissue and/or bodily fluids and exosomes as sources for discovery. BDLs may also develop new technologies to detect candidate biomarkers, integrate them with imaging methods, and work collaboratively with other EDRN laboratories to combine biomarkers for improving the test performance. Applicants may also consider using bioengineered tools and technologies to develop synthetic biomarker-based diagnostic tests.
The objectives include, but are not limited to, the following:
As mentioned earlier, the key to discovery is to ensure that these platforms are amenable to clinical use and supported through CLIA regulations. Describe the development of rigorous study design and study protocols applicable to the proposed BDL, including robust data collection and quality control procedures. Some examples that illustrate the specific types of translational biomarker studies that could be conducted while taking advantage of technological advances to accelerate quantitative biomarker discovery to clinical translation include, but are not limited to, the following.
(B) Biostatistics, Bioinformatics and Data Modeling:
Applicants should propose their discovery studies based on the EDRN-established Phase 1 and Phase 2 biomarker development guidelines and PRoBE (http://edrn.nci.nih.gov/docs) or a similar rigorous study design to avoid bias and make best use of available resources. This will strengthen discovery research and increase the likelihood of reproducibility of results. In addition, a clear statement is required on how statistical power is defined in multiple tests and what sample size is required to achieve this power. Examples of power definition include: (a) the probability to detect at least one of possible true non-zero effects; (b) the probability to detect all non-zero effects; and (c) true discovery rate etc. Also, in case-control designs, clear descriptions are required of whether matching is involved and what cofounders are adjusted for, and why.
Applicants are encouraged to apply a "precision discovery" approach using bioinformatics and AI tools (MLL, deep learning) for data mining/analysis of large datasets (GWAS, The Cancer Genome Atlas [TCGA], Pre-Cancer Atlas [PCA], if available, etc.) and extract the molecular know-how/key biomarkers associated with a clinical phenotype of interest to the BCC and integrate into their discovery platform(s). This approach may strengthen the study. In addition, leverage, where feasible, technology from related NCI-sponsored informatics initiatives, for example, the NCI Informatics Technology for Cancer Research (ITCR; https://itcr.nci.nih.gov/) program, which supports the development of informatics algorithms, tools, and resources across the continuum of cancer research.
Applicants are also urged to use computational/mathematical data modeling approaches to predict the translational efficacy of the proposed biomarkers as this will ensure a greater chance of success in downstream validation phases and reaching the clinic. EDRN expects that applicants will develop active collaborations with investigators supported by the NCI CISNET program (http://cisnet.cancer.gov/index.html); such collaborations may enhance the discovery efforts by identifying opportunities for precision screening/early detection, provide a better understanding of real-world clinical settings and needs, and also support the development of statistical modeling and simulation models to evaluate the impact of the proposed biomarker tests.
Sub-section D: Preliminary Data
Use this sub-section to present preliminary data addressing, minimally, the following aspects of the BDL:
Sub-section E: Informed Consent
In this sub-section, provide details about the breadth of informed consent obtained from patients. Careful attention must be paid to the design of patient consent forms at the time of specimen collection. Consent forms must allow for data sharing as required by the NIH and the EDRN. Include an approved consent form in the Appendix materials or provide evidence that approval is expected.
Sub-section F: Annual Milestones
The following major benchmarks of progress must be addressed. Any application lacking acceptable milestones will be considered incomplete.
a) Applicants should provide a clear set of annual, quantitative benchmarks for each specific aim of BDL associated with timelines.
b) These milestones must be well described, quantitative, and scientifically justified. Discuss the milestones as a means of judging the success of the proposed studies in the first 3 years of the U2C award period. Specific aims may not be regarded as milestones (unless they include quantitative end points). The specific aims describe the goals and intended path of the proposed research. Quantitative milestones are a way of determining whether an applicant has successfully reached the specified goals. Generally, applicants are expected to provide milestones for each specific aim. Milestones should be clearly stated and presented in a quantitative manner, such as numerical specifications of sensitivity and specificity or a count of some newly discovered molecules or molecular pattern(s) that can be used as biomarkers for early cancer detection, risk assessment, diagnosis or prognosis of cancer.
Examples of quantitative milestones are listed below:
c) Applicants should also elaborate on a decision-tree scheme to be used during biomarker developmental studies for triaging biomarker candidates, as well as the criteria based on which specific biomarkers should continue to be pursued ( go or no go decision). Should certain promising biomarkers be dropped at any stage during development, alternative steps or strategies to be followed must also be described.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Resource Sharing Plans should only be included in the Overall component, as instructed before.
Appendix:
Only limited items are allowed in the Appendix.
Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions. Applicants should not use the Appendix to circumvent page limits.
PHS Human Subjects and Clinical Trials Information (BDL)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
Biomarker Reference Laboratory (BRL)
When preparing your application, use Component Type Core - Biomarker Reference Laboratory
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.
SF424 (R&R) Cover (BRL)
Complete only the following fields:
PHS 398 Cover Page Supplement (BRL)
Enter Human Embryonic Stem Cells in each relevant component.
Research & Related Other Project Information (BRL)
Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations?
Vertebrate Animals: Answer only the Are Vertebrate Animals Used?
Project Narrative: Do not complete.
Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.
Project /Performance Site Location(s) (BRL)
List all performance sites that apply to the specific component.
Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachments for additional entries.
Research & Related Senior/Key Person Profile (BRL)
Budget (BRL)
Budget forms appropriate for the specific component will be included in the application package.
Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.
PHS 398 Research Plan (BRL)
Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.
Specific Aims: Outline specific aims for the BRL and provide a rationale and description of how each aim addresses a specific aspect of the overall development of new biomarker assays or refinement of existing assays for a clinically unmet need that the BCC is addressing. The aims should be consistent with the practice of a typical reference laboratory but should also ensure sufficient flexibility needed for changing and expanding needs of EDRN.
Research Strategy: In lieu of the standard Research Strategy sub-sections (e.g., Significance, Innovation, Approach), use the sub-sections defined below to describe the activities of this functional component.
Applicants must also review Section I. Funding Opportunity Description for expectations from the BRL component.
Sub-section A. Overview
Outline how the proposed BRL component will provide the anticipated lines of laboratory support for the core responsibilities that include:
Describe that the BRL is able to follow CLIA/CAP/GLP/GMP-compliant guidelines to ensure consistency and reliability of results. Applicants should document, when appropriate, compliance with guidelines that govern GLP, as defined by 21 CRF (58), and Current GMP, as defined by 21 CRF (211), manufacturing and/or investigational new drug (IND)/investigational device exemption (IDE) enabling studies that will be performed under the award as they would be applicable to eventual product licensure in the U.S. Applications for projects involving cGMP manufacture should ensure inclusion of appropriate personnel to provide regulatory guidance before, during and after manufacture.
Applicants should address, but not be limited to, the following specific aspects:
Sub-section B: Specific Plans for the Main Areas of Responsibility
BCC Specific Functions:
The proposed diagnostic assays must be designed to detect the target analytes in tissue, blood (serum, plasma), and other bodily fluids. The proposed diagnostic platforms and/or technologies must be supported by proof-of-concept data demonstrating the feasibility and meeting Phase 1 and Phase 2 criteria of the five-phase biomarker development approach and PRoBE (or similar) principles. Such biomarkers or analytes may also come from existing ongoing EDRN discoveries.
Briefly explain the rationale of the proposed development(s) of previously identified candidate diagnostic technology(s), including proof-of-concept data demonstrating feasibility. Describe the development of rigorous study design and study protocols applicable to the proposed BRL (including robust data collection and quality control procedures). Include the following:
Network Collaborative Studies:
Explain the strategy to ensure that the BRL can meaningfully contribute to collaborative studies and assist Network partners in such activities as:
The BRL component may be asked by the Steering Committee to conduct studies on a variety of assays in order to improve their performance characteristics. Based on the capabilities of the proposed BRL and the knowledge and experience of its investigators, describe:
Explain to what degree these strategies and approaches will be applicable to:
As a collaborative resource of the Network, BRLs will be expected to facilitate the discovery, clinical validation, and clinical application of biomarkers through participation in collaborative Network studies with other BCCs and/or CVCs. Outline your anticipated role(s) in this context. Examples of collaborative projects include but will not be limited to the following:
Sub-section C: Development of Reference Materials, If Applicable
Applicants must provide details for developing reference materials for controls in molecular assays/technologies, such as NGS and/or quantitative proteomic analysis and/or extracellular vesicle (exosome)-based isolation and characterization, and/or other technologies that are of great importance for proficiency testing. A BRL may be asked to develop and/or test such reference materials at the onset of analytical validation of specific biomarkers.
Sub-section D: Industry Participation
The BRL can be in part or completely run by a qualified industrial lab. The BRL from academic institutions is required to demonstrate substantive participation in the project by at least one industry participant. For the purpose of this FOA, "industry" is defined as domestic, large or small, pharmaceutical, biotechnology, bioengineering, and/or chemical companies, or non-profit agencies with demonstrated experience in product development. Substantive participation" is defined as a commitment of one or more resources including, but not limited to: product/prototype development support/guidance; personnel; in-kind contributions of materials and/or reagents (i.e., diagnostic analytes, innovative biotechnology platforms, material/reagent scale-up, etc.); or regulatory support.
Sub-section E: Preliminary Data
Use this sub-section to present preliminary data addressing, minimally, the following aspects of the BRL:
Sub-section F: Annual Milestones
The following major benchmarks of progress must be addressed. Any application lacking milestones will be considered incomplete.
a) Applicants should provide a clear set of annual, quantitative benchmarks for each specific aim of BRL associated with timelines.
b) These milestones must be well described, quantitative, and scientifically justified. Discuss the milestones as a means of judging the success of the proposed studies in the first 3 years of the U2C award period. Specific aims may not be regarded as milestones (unless they include quantitative end points). The specific aims describe the goals and intended path of the proposed research. Quantitative milestones are a way of determining whether an applicant has successfully reached the specified goals. Generally, applicants are expected to provide milestones for each specific aim. Milestones should be clearly stated and presented in a quantitative manner, such as numerical specifications of sensitivity and specificity or a count of some newly discovered molecules or molecular pattern(s) that can be used as biomarkers for early cancer detection, risk assessment, diagnosis or prognosis of cancer.
Examples of quantitative milestones are:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Resource Sharing Plans should only be included in the Overall component, as instructed before.
Appendix:
Only limited items are allowed in the Appendix.
Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions. Applicants should not use the Appendix to circumvent page limits.
PHS Human Subjects and Clinical Trials Information (BRL)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
4. Submission Dates and Times
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
6. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
7. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.
The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this FOA, note the following:
Functional Component BRL: The BRL component will be evaluated by each reviewer but will receive only one overall numerical score.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the proposed Center address the needs of the research network that it will serve? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research network
Specific to this FOA:
What is the likelihood that the proposed research will succeed in moving biomarkers to EDRN-established Phase 2 and/or Phase 3 validation during the next five years?
For the proposed product development, does the applicant address an important need for technology, reagent, and other resource development, standardization, quality control, or protocols suitable for risk assessment, detection, molecular diagnosis and prognosis of early cancer?
How likely will the proposed biomarkers be useful to population of the United States, including minority health and NIH-designated populations that experience health disparities ?
Investigator(s)
Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing biomarker research? Do the investigators demonstrate significant experience with coordinating collaborative biomarker translational research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?
Specific to this FOA: To what extent does this team of investigators show a significant measure of success in experimental approaches to biomarker discovery and development for assessment, detection, diagnosis and prognosis of early cancers? Do the investigators have extensive expertise in human cancer biospecimen collection, handling, characterization, assay development? To what extent are the key personnel and team organization suitable for integrating the BDL and BRL functions and meeting the goals of the BCC as well as the Network? Is the commitment of the PDs/PIs and other key personnel in line with the scope of the proposed project? Is there evidence that the PDs/PIs and other team members have effectively worked together in the past? How well do the proposed interactions and collaborations among the BCC PDs/PIs and other key personnel unite the components and advance the biomarker development effort?
Innovation
Does the application propose novel organizational concepts and biomarker development strategies in coordinating the research network the Center will serve? Are the strategies novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of biomarker development strategies proposed?
Specific to this FOA: If applicable, how clearly does the applicant delineate the integration of molecular, imaging and/or clinical information toward biomarker discovery?
Approach
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?
Specific to this FOA:
To what extent are the target population and clinical setting for the intended use of the biomarker clearly defined?
How strong is the rationale for the product development/proposed deliverables? How clearly has the applicant described the source of high quality, clinically-annotated biospecimens?
Do the biospecimens meet the requirements of PRoBE or a similar rigorous study design?
Is it clear how the marker performance will be evaluated?
To what extent are parameters, such as sensitivity, specificity and predictive value, chosen to characterize the biomarkers/reagents sufficient and appropriate?
To what extent are the provided milestones and timelines appropriate for the success of the product development strategy and do they allow for an evaluation of the progress of the BCC on the proposed product development?
To what extent are the knowledge base and practices of biomarker discover/development and assay validation adequate for meeting the requirements of the BCC? How adequate are the plans for effective interaction and coordination with other Network units (i.e., CVCs, DMCC), the Steering Committee, and the NCI?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Environment
Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling
Specific to this FOA:
To what extent are the primary resources for the proposed study within the laboratory under the direct oversight of the PDs/PIs?
To what extent are appropriate facilities and infrastructure (including equipment for high-throughput testing) available to the applicant’s team?
If collaboration with a private sector entity is proposed, will such collaboration be beneficial to the BCC goals and to the mission of EDRN? To what extent will the proposed BCC be a truly integrated entity, rather than a collection of unrelated research ventures and support services?
How well does the BCC organization promote scientific and administrative integration, synergy and a cohesive research goal?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Review Criteria - Administrative Core
Reviewers will consider the following aspects while determining scientific and technical merit of this component:
Review Criteria - BDL
Reviewers will provide only one overall numerical score for the BDL (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:
Review Criteria - BRL
Reviewers will provide only one overall numerical score for the BRL (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable.
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Not Applicable
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For networks involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in theNIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Prior Approval of Pilot Projects
Recipient-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR 200, and other DHHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below
The PDs/PIs will have the primary responsibility for:
PDs/PIs Responsibilities for Network Collaborative Studies:
NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
A designated NCI Program Official serving as the Project Coordinator will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may also become substantially involved as needed. An NCI Program Director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Additional Program Officials who are not responsible for the normal scientific and programmatic stewardship of the award may be designated as Project Scientists and assist in Network activities.
The specific roles of the substantially involved NCI staff members include the following activities:
The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to those Network awardee institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.
Areas of Joint Responsibility include:
Steering Committee: The Steering Committee will be the main governing body for the EDRN. The EDRN Steering Committee will convene after all the Network units have been funded and will be composed of the following voting members:
Each voting member will have one vote.
Additional NIH staff may participate in Steering Committee meetings as non-voting members as needed (for example to provide additional expertise). The non-voting members may include representatives from NCI extramural divisions and a representative from the NCI CBIIT.
Additional non-voting members may participate on the Steering Committee in an advisory capacity on an as needed basis and decided by the existing voting committee members.
The Chair of the Steering Committee (who cannot be an NIH staff) will be selected by the Steering Committee.
The Steering Committee will meet twice every year, at locations selected by the Steering Committee in consultation with the NCI.
The Steering Committee may establish subcommittees for specific purposes. The NCI Project Coordinator/Scientists and Program Officials will serve on such subcommittees, as appropriate.
Primary responsibilities of the Steering Committee include, but are not limited to, the following activities:
Network scientific, operational, and organizational policies and procedures, are also described in the EDRN MOP (https://edrn.nci.nih.gov/about/bookshelf).
Dispute Resolution Process
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Sudhir Srivastava, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7028
Email: srivasts@mail.nih.gov
Sharmistha Ghosh-Janjigian, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7122
Email: ghoshjanjigias@mail.nih.gov
Matthew Young, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5846
Email: matthew.young@nih.gov
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov
Amy R. Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6912
Email: amy.bartosch@nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.