It is critical that applicants follow the Research (R) 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for a Data Management and Coordinating Center (DMCC), one of the three scientific units of the Early Detection Research Network (EDRN). The EDRN (http://edrn.nci.nih.gov/) is an integrated infrastructure to discover, develop, and validate biomarkers and imaging methods for early cancer detection and risk assessment. The proposed DMCC will be responsible for the following activities: 1) Network Coordination, 2) Data Science, Data Management and Study Protocol Development, 3) Validation Study Infrastructure and Services, and 4) EDRN Core Fund Management.

In addition to DMCC (this FOA), EDRN includes the following two scientific units, each supported by an independent FOA:

• Biomarker Characterization Centers (BCCs) (RFA-CA-21-035), will have two functional components (1) a Biomarker Developmental Laboratory, which will discover, develop, characterize and test new biomarkers or refine existing biomarkers and(2) a Biomarker Reference Laboratory, 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.
• Clinical Validation Centers (CVCs) (RFA-CA-21-033), 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 expertise and ability to conduct clinical utility trials of validated early detection biomarkers and/or imaging methods.

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.

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, http://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 relies 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 (IC) at JPL 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 for 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:

• Discover, develop, evaluate, and validate promising 'omic' biomarkers (e.g., genomic, proteomic, epigenomic, metabolomic) for effective cancer risk assessment, early detection, and diagnosis and prognosis of early stage cancers and preneoplastic lesions.
• Develop and validate biomarkers to improve the detection of cancer progression for patients on active surveillance.
• Develop and implement diagnostic assays/tests for accelerating biomarker discovery and translation into the clinic. This would include measures of diagnostic or predictive accuracy, sensitivity, specificity.
• Facilitate the development of high-throughput, sensitive assay methods to identify, verify and validate biomarkers that are useful in assessment of risk, detection, diagnosis and prognosis of early stage cancers or their lethal precursors.
• Integrate molecular biomarkers with imaging approaches to improve performance of tests, reduce false positive rates, and improve detection of clinically significant cancers.
• Implement, expand and/or modify new or existing imaging modalities, protocols, and associated informatics to improve performance of tests.
• Develop and implement artificial intelligence (AI) and machine learning (ML) algorithms to facilitate the discovery and translation of multiplex biomarkers'
• Support collaboration among academic and industrial leaders, whose areas of interest are in molecular biology/molecular genetics, imaging, data science, clinical oncology, public health and/or other related areas, leading to the development of early cancer diagnostics.
• Conduct clinical/epidemiological studies (e.g., cross-sectional, prospective, retrospective) in order to evaluate the predictive value of biomarkers.
• Improve the informatics infrastructure to facilitate precompetitive data and/or image sharing on biomarker discovery, development, and validation.
• Serve as a core resource so that NCI and the cancer community at large can leverage the well-developed EDRN infrastructure and expertise in order to facilitate translational cancer research, clinical utility trials, and cancer prevention and therapeutic trials.

These goals are achieved through an integrated and systematic 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 (http://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 biomarker from the laboratory to the bedside. The five phases for biomarker discovery and validation are:

• Phase 1: The preclinical exploratory phase;
• Phase 2: The clinical assay validation phase (case-control);
• Phase 3: The retrospective longitudinal validation phase;
• Phase 4: The prospective screening phase; and
• Phase 5: The cancer control phase.

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 five-phase approach and PRoBE study design are available on the EDRN website (http://edrn.nci.nih.gov/about/bookshelf).

EDRN will be structured around the three main scientific units BCCs, CVCs and DMCC. Although individual teams of EDRN awardees (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 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 BCLs 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 making the Network inclusive by supporting Associate Members. 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 administered by DMCC and will be restricted via a term of award pending review 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. Final review and selection of requests to be recommended for funding will be conducted by the 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.

Data Science: Despite unprecedented technological advancements, only a handful of cancer biomarkers make it through regulatory approval or clearance every year. Inadequate data infrastructure and statistical or bioinformatics rigor have been identified as key contributing factors as this lag in clinical translation of promising candidate biomarkers. High dimensional, high throughput data originating from omic, technologies, digitization of pathological images and other approaches require collection, storage, and integration. Analysis of large, heterogeneous, structured and unstructured data sets, and new computational methods such as advanced deep learning, digital phenotypes, machine learning and artificial intelligence, and 3D imaging are expected to transform biomedical and behavioral research and lead to improved health for individuals and populations. Additionally, traditional datasets, e.g. national health systems, surveillance, surveys are becoming deeper and richer while new sources of data based on new technologies are emerging that may be of greatest value when linked to biomarker data science.

Scope. This FOA encourages the submission of applications to establish and enhance the EDRN DMCC. The DMCC must have expertise and capabilities in biostatistics, computational analysis, imaging, modeling, information technology, bioinformatics, data management, protocol development, and in coordinating and providing logistical support for meetings and conferences. DMCC is expected to evolve, adapt and improve in response to the needs of the EDRN community. It is essential that the DMCC applicants familiarize themselves with the companion FOAs for the other EDRN units with which the DMCC must work: BCC (RFA-CA-21-035) and CVC (RFA-CA-21-033).

DMCC responsibilities include but are not limited to:

• Provide statistical analysis for EDRN-collaborative validation studies.
• Support the development, coordination, implementation, and conduct of EDRN-collaborative research protocols, including EDRN-sponsored multi-center biomarker validation studies.
• Support NIH Single-IRB policy to enhance and streamline the IRB process for multi-site research studies.
• Deploy state-of-the-art management of data and protocol development, Laboratory Information Management System (LIMS), which provides a comprehensive array of support services including study development, documentation of CDEs, development and distribution of biospecimens, data entry checks, study-specific reports, specimen tracking, monitoring and selection, eligibility programming and ongoing remote study staff support and data harmonization. The LIMS must be flexible and adaptable using modern Cloud-based extensions to quickly support the various EDRN studies, for which a collaborator with necessary expertise may be appropriate.
• Collaborate and provide relevant contents for JPL-developed informatics infrastructure services for biomarker development (e.g., EDRN Catalog and Archive Service (eCAS), EDRN Study Information System (eSIS), EDRN Biomarker Database (http://edrn.nci.nih.gov/). Some of these activities will be conducted in partnership with the EDRN Informatics Center JPL.
• Work closely with EDRN investigators to support data analysis, modeling, and utilize visualization tools. Additional consultations and support on statistics and modeling will be made available through the NCI Division of Cancer Prevention's Biometry Research Group as directed by Steering Committee and NCI staff.
• Enhance, improve and maintain Network integration and coordination.
• Provide logistical and administrative assistance in arranging Network-wide meetings and workshops and employ various electronic channels of communication to promote and disseminate information among EDRN investigators and the broader scientific community.
• Manage the EDRN Core Fund.
• Collect, store, curate, and disseminate all data, metadata, analysis and visualization tools, and computational models and lead the development of common data elements, data and metadata standards, clinical and epidemiological data requirements, and data processing pipelines.

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.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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.

An investigator designated as a Contact PD/PI of an application under this FOA must not be the designated Contact PD/PI, MPI, or co-PI of any of the EDRN companion FOAs.

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. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. 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.

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:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Sudhir Srivastava, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7028
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy must not exceed 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. Additional instructions are defined below.

Other Attachments: Applicants should provide additional supporting materials relevant to the proposed DMCC defined below. Upload these materials as a pdf file using the indicated file name (this file name will become a bookmark in the application).

• Filename: "Validation Studies": Provide supplemental data documenting your recent research contributions relevant to biomarker or imaging validation studies.

All instructions in the SF424 (R&R) Application Guide must be followed. All Key Personnel must provide a detailed description of their expertise that is relevant to the proposed services and responsibilities.

Specifically, describe the knowledge and experience of the PD(s)/PI(s) and other Senior/Key Persons in cancer research, technologies for cancer detection, imaging, informatics, and computational data science.

All instructions in the SF424 (R&R) Application Guide must be followed.

The following additional instructions apply:

a) Of the total requested budget, no more than $1.8 million per year (direct costs) may be allocated to the activities of DMCC. The reminder (up to $6 million per year) must be allocated to the restricted Network Core Fund (see below).

b) PD(s)/PI(s) Effort: The contact PD/PI must commit a minimum of 1.2 person-months effort per year to the U24 award. This commitment cannot be reduced in later years of the award. For multiple PD/PI applications, the other PD(s)/PI(s) must devote a minimum of 1.2 person months effort per year.

c) Network Core Fund: Applicants must include $4.2 million in direct costs for the restricted Network Core Fund in the budget request for FY2022 and $6 million in direct costs for the restricted Network Core Fund in the budget request for FYs 2023-2026. This amount should be presented in the Other Direct Costs category under the heading Network Core Fund". The awarded DMCC will manage this restricted fund as described in this FOA. The exact dollar amount for Core Fund will be determined by the NCI at the time of award.

These funds will be restricted via the Terms and Conditions of the award to support post-award collaborative research projects involving EDRN awardees (including the DMCC awardee) as well as non-EDRN investigators as recommended by the EDRN Steering Committee and approved by the NCI.

d) Network Collaborative Funds: Applicants must set aside 30 percent of their annual budget for DMCC operations (i.e., excluding the Core Fund allocation) for Network collaborative studies. In the case of renewal application, the amount set aside should include the funds already approved by NCI for ongoing validation studies. The set aside amount should be presented in the Other Direct Costs category under the heading Network Collaborative Funds".

The use of the set-aside funds will be restricted for collaborative studies proposed post-award and must be reviewed by the Steering Committee. The release of these restricted funds will be contingent upon the advice of the EDRN Executive Committee and authorization by the NCI

Currently, EDRN has ongoing Network collaborative validation studies, biospecimen reference set collections, and NCI anticipates that in the future in any given year the DMCC will coordinate approximately six (6) Network trials involving on average 10 study sites and biospecimen reference set collections.

Note: If the number of Network trials exceeds the above estimates, additional funding may be allocated from the EDRN Core Fund.

e) Restricted Travel Expenses Budget: Applicants must budget for travel and per diem expenses for EDRN meetings and workshops. The contact PD/PI together with at least one MPI or a senior investigator and an early-stage/junior investigator will attend the Planning Meeting and two Steering Committee meetings in the first year, two Steering Committee meetings in each of the subsequent years of the award, and one EDRN-sponsored scientific workshop every 18 months (this usually coincides with one of the Steering Committee meetings).

Other Budget-Related Information: Budget for personnel services directly involved in the activities of the DMCC should be clearly identified. Applicants should budget to cover the types of services listed below. The workload in each category will vary as the needs and priorities of the EDRN change during the funding period. The applicant’s staffing plan must allow for the flexibility needed to adapt to these changes.

1) Administrative Services:

• Team Leader's and other PD(s)/PI(s)' time to administer the center and EDRN projects;
• Logistical arrangements and support for two Steering Committee meetings and one Network Consulting Team meeting every year, and one scientific workshop every 18 months. Applicants must budget $50,000 (direct cost only) each year for reserving a site for the Steering Committee and the Network Consulting Team meetings and other related expenses. The place and dates for the meetings will be decided by the NCI Project Coordinator in consultation with the Steering Committee. The use of these funds is restricted and must be reviewed and approved by the Steering Committee and NCI. The Steering Committee meetings/workshops are three-day long for approximately 200 attendees. The Network Consulting Team meeting is a one-day meeting with approximately 20 participants;
• Monthly conference calls for the Steering Committee executive leadership (Executive Committee) (arrange and keep minutes);
• Online review of Associate Membership applications (approximately 6 applications, three times per year) and validation study proposals submitted to the EDRN;
• Conduct NIH Single-IRBs to enhance and streamline the IRB process for multi-site research studies.

2) Informatics Services:

• Develop and maintain secure website to allow for communication among EDRN members and posting of study results;
• Develop tools for biomarker validation in collaboration with JPL;
• Support data analysis, computational models and visualization tools;
• Develop user manuals and tutorials for EDRN Public and Data Portals;
• Transfer of databases and informatics programs or tools to the NCI-hosted EDRN public portal when requested to do so by the NCI Project Coordinator.

3) Statistical Analysis and Study Protocol Development Services:

• Assist in the design of Network collaborative validation studies (data collection and entry, sample tracking, calculation of populations and power analysis) and perform statistical analysis on data;
• Assist in the design of Network specimen reference set collections (data collection and entry, sample tracking, calculation of populations and power analysis);
• Assist in data science projects, i.e., computational tools for data mining, machine learning, big data, and modeling.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Sub-section A: Overview

DMCC serves as a scientific and organizational hub to the entire Network. In light of this significance, applicants must describe the innovation of the proposed strategies for early cancer detection, risk assessment, diagnosis, and prognosis. Without repeating information in the Biographical Sketches of individual investigators, highlight the main scientific and organizational strengths of the proposed DMCC in (but are not limited to) the following areas:

• Advanced computational biology capabilities (including statistical and mathematical data analysis, the ability to develop new methods/tools for biomarker research relevant to cancer detection, diagnosis and prognosis, modeling, visualization tools);
• Rigorous study design and development of study protocols applicable to multi-center collaborative studies (including robust data collection and quality control procedures); and
• Experience in management of large-scale collaborative research efforts involving multiple institutions (including logistical services and organizational support).

To address how the DMCC activities will be matched with the anticipated trans-Network needs, the applicants must provide a description of the proposed DMCC as follows:

• Describe the organization of the proposed DMCC and the team's strengths in biostatistics, data management, data analysis, data science, imaging, and project management skills;
• Explain how the team will integrate and capitalize on the expertise of its members in protocol design, data entry procedures and manual preparation, and in data collection and data quality control for largescale, complex research projects;
• Describe how logistical services and organizational support will be utilized in managing resources and monitoring performance in large-scale, collaborative research.

Sub-section B: Previous Accomplishments

Relevant Recent Accomplishments (all applications): Describe previous research accomplishments/preliminary studies relevant to biomarker and imaging method development and validation and the responsibilities of the proposed DMCC. The description should address (but is not limited to) the following aspects:

• Implementation of statistical and computational tools in biomarker and imaging development and validation studies;
• Record of generating reports on data collection and performance in previous large-scale collaborative projects, including preparation of manuscripts; and
• Organization and coordination of multi-institutional activities (e.g., meetings).

Progress Report (renewal application only). Include additional information in this section summarizing the current 5-year funding period and include the following items:

a) List the specific aims from your previously funded application. Describe the progress made relevant to these specific aims and indicate the status of developed markers according to the EDRN-defined biomarker phases. Applicants should highlight their progress using the EDRN-developed Evaluation Metrics as described in the EDRN Manual of Operations (http://edrn.nci.nih.gov/docs).

b) Describe the progress made on biomarker research supported by other EDRN funding sources such as projects funded through the restricted set-aside funds or the EDRN Core Fund. If the applicant has participated in any Network-wide validation studies or other projects supported by the EDRN Core Fund, elaborate on the role(s) played and the contribution(s) made to the outcome of the studies.

Note: Supplementary data for this sub-section are requested under "Other Attachments" in Section IV.2. Content and Form of Application Submission.

Sub-section C: Plans for the Required Areas of Responsibility

The DMCC will work closely with the NCI Project Coordinator and be responsible for the following major activities: 1) Network Coordination, 2) Data Science, Data Management and Study Protocol Development, 3) Validation Study Infrastructure and Services and 4) EDRN Core Fund management. Applicants must describe in detail the development, implementation, and maintenance plans for each required area of responsibility. These plans should include description of design, personnel requirements, and infrastructure (hardware, software, other). Applicants are encouraged to describe in their application the cost-efficient use of existing technologies. Also describe an approach to ensure flexibility and facilitate implementation of statistical and/or analytical approaches beyond those specified in the application. Provide the anticipated needs of research projects for statistical/analytical tools for study design, data analysis, and interpretation.

Describe how the DMCC will conduct the four major areas of responsibility.

1. Network Coordination and Outreach

• Provide logistical and administrative assistance in arranging meetings of the Steering Committee, the executive leadership of the Steering Committee (Executive Committee), and the Network Consulting Team (e.g. preparing, distributing, and maintaining minutes of meetings). There will be two face-to-face Steering Committee Meetings per year, one NCT meeting per year, and monthly teleconferences of the Executive Committee;
• Provide logistical and administrative support in arranging workshops there will be one scientific workshop every 18 months, which occurs in conjunction with a Steering Committee meeting;
• Provide other operational support for the Network (e.g., communications, subcommittee meetings, teleconferences);
• Employ various electronic channels of communication to promote and disseminate information among EDRN investigators and the broader scientific community;
• Produce and maintain all documents, including Manual of Operations and procedure manuals;
• Contribute to the development, upgrading, and maintenance of an interactive EDRN website to disseminate information on important accomplishments of the Network, and to publicize the availability of EDRN-supported resources;
• Develop and maintain a "listserv" interactive email system for communication within the Network;
• Work with the NCI Project Coordinator on the review of Associate Membership applications/validation study proposals submitted to the EDRN Steering Committee.

2. Data Science, Data Management and Study Protocol Development (conducted under the direction of the Steering Committee)

• Support the development, coordination, and implementation of EDRN collaborative research protocols, including EDRN-sponsored multi-center biomarker and/or imaging validation studies;
• Provide statistical support for EDRN-collaborative validation studies;
• Conduct data analysis and assist in the publication of results of EDRN collaborative validation studies;
• Demonstrate the expertise and flexibility to accommodate increasing data volume/types from EDRN studies (bioinformatics, imaging, data science, modeling, visualization tools, etc.);
• Describe plans to support and implement analysis and visualization tools developed by DMCC investigators, i.e. tools and software that are modular, open-source, use standard formats for data input and output, and are considered likely to be broadly useful to EDRN investigators;
• Describe whether the proposed approaches are generally applicable to the statistical analysis of data related to the development of biomarkers and reagents;
• Develop worksheets and information management systems for collection of data and/or images in multi-center biomarker validation studies, verify all data, perform statistical tests, and maintain software for within-form edit checks at data entry;
• Monitor Network protocol adherence, data collection and data submission, and report violations to the Steering Committee;
• Assist in the collection of epidemiological information, data analysis, study designs, quality assurance for a central database, statistical analysis of pooled data, and distribution of specimens stored at sites participating in the Network;
• Assist in the collection of imaging studies, i.e. deidentification, storage, and subsequent transfer to NCI designated repositories;
• Develop uniform investigative protocols for data and specimen collection;
• Support the collection, assembly and distribution of EDRN biospecimen reference sets and analyze data that result from the use of these specimens;
• Develop and maintain a computerized data system for data management and statistical analysis;
• Ensure that data are collected to determine the benefits and risks that follow from positive or negative test results;
• Provide support services for the production of data forms and reports, graphics, and other materials as required;
• Provide a mechanism for rapid and routine (to be decided by the Steering Committee) transmittal of materials (e.g. computer output, reports, etc.) among the Network participants and the NCI Project Coordinator and other NCI staff;
• Provide advice and consultation to EDRN investigators in study design and protocol development of EDRN collaborative validation studies, after the study has been approved by the EDRN Steering Committee;
• Capture and deposit consequential data sets developed by the EDRN to JPL as decided by the Steering Committee;
• Curate and deposit data in the Biomarker Data Commons, LabCAS (https://edrn.nci.nih.gov/data-and-resources/informatics), developed by JPL;
• Demonstrate expertise in data mining using AI and bioinformatic tools;
• Utilize data analytics (statistics, AI, MLL, Deep Learning, bioinformatics tools, etc.) to improve the understanding of the disease progression as well as new aspects of biomarker discover for early detection.

3. Validation Study Infrastructure and Services

The NCI has an Interagency Agreement with NASA's JPL (EDRN Informatics Center; IC) to assist the EDRN in building information technology infrastructure of integrated databases, webpages and informatics tools. The DMCC will work closely with the NCI and the EDRN IC in the specification and design of software for the development of a Network-wide informatics enterprise. While the DMCC will take the lead in maintaining and developing resources for the EDRN Secure Website for data security, data warehouse with interfaces, and data analysis for Network supported validation studies, the EDRN IC will take the lead in implementing the distributed Network-based data warehouse, tools and interfaces for publicly-accessible information. DMCC and EDRN IC will work closely with NCI staff and the NCI Center for Biomedical Informatics and Information Technology (CBIIT).

The responsibilities of DMCC toward the development of the EDRN biomarker database include, but not limited to, the following:

• Prepare and produce data collection forms on biomarkers and/or images in collaboration with the EDRN IC;
• Develop quality control procedures for the handling of biomarker data and update files with error corrections, etc. as directed by the EDRN Steering Committee;
• Specify, capture and annotate EDRN scientific data from selected studies. Data for description and/or capture are at two levels: instrument (specific instruments at bench or in clinic, which generate EDRN biomarker data), and biomedical and clinical data at the database level;
• Feed specifications back for integration into ontology models. Specifically, work on the development of metadata and review the ontology for the data captured at all levels of processing from the bench to the database to clinical work;
• Collaborate with the EDRN IC to modify ontology models as needed;
• Collaborate on common system designs or protocols with the IC and NCI, including methods and requirements for populating the databases and handling of data, including appropriate sharing of methods and data among collaborating organizations.

All publicly accessible resources and tools developed by the DMCC and EDRN IC are integrated into the NCI-hosted EDRN public portal (http://edrn.nci.nih.gov/). Such resources and tools include but are not limited to CDEs (with a subset linked to specific protocols), CDE mapping tools, Form-generating tool, ERNE, LIMS, study protocols, Manual of Operations, list of biomarkers and their phase of development within EDRN, and the storage of data from studies. See the following reference for data sharing:

http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html (http://grants1.nih.gov/grants/guide/noticefiles/NOT-OD-03-032.html). DMCC will work closely with the EDRN Informatics Center in expanding and/or updating these resources to meet the growing needs of EDRN in the future.

4. Management of Core Fund

DMCC will administer the EDRN Core Fund. The use of the Core Fund will be restricted to support Network-wide collaborative studies, and other resource-related activities, as well as third party consortia to support EDRN validation trials, including patient accrual and collection of specimens. For activities reviewed and recommended by the EDRN Steering Committee (via Executive Committee) and approved for funds release by the NCI, the DMCC will activate funds from the Core Fund by establishing appropriate sub-contractual arrangements with the institutions of the investigators involved.

The applicants must confirm that their institution has appropriate management infrastructure (through its Office of Sponsored Research or equivalent) capable of managing government grants and contracts. This infrastructure must be adequate to manage multiple sub-contractual arrangements expected for the authorized uses of the Core Fund (approximately 20-50 subawards per year). DMCC will work closely with the EDRN Steering Committee and the NCI Project Coordinator on the management of the Core Fund. In support of their ability to manage and disburse the core fund, the applicant should describe:

• The current subaward process at their institution;
• Timeline for the disbursement of Core Fund from the time NCI OGA releases the fund to DMCC to the transfer of fund to sub-awardees;
• Methods to track and monitor subawards on a quarterly basis and to generate reports for the NCI staff;
• Administrative process to identify an unforeseen situation, e.g., such as identifying potential delays proactively and working to mitigate in collaboration with the NCI staff;

NOTE: Investigators interested in applying for the DMCC award may request access to information on current EDRN architecture and bioinformatics tools by contacting the NCI Project Coordinator for the EDRN (Email: [email protected]).

Transition Plan. The incumbent DMCC institution must provide a detailed transition plan and the cost involved in transferring data, software for information technology infrastructures, databases, analytical tools, and other relevant documents resulting from EDRN activities (e.g., Steering Committees, Workshops, Subcommittees, etc.), to the NCI and to the new DMCC awardee. This transition plan will only be implemented if the incumbent is not recommended for continuation, and it should include, but is not limited to:

• Convening a transition team;
• Inventory of the materials to be transferred;
• A time-line for the transfer;
• A post-transfer meeting for closing out the transfer.

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.

In addition to the standard NIH rules, the following EDRN-specific expectations apply:

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 (http://edrn.nci.nih.gov/docs (http://edrn.nci.nih.gov/docs)). 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.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 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.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

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). 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.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number 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 and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-19-083 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 particular announcement, note the following:

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.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Will the proposed statistical and computational approaches advance the field of biomarker development for risk assessment, detection, diagnosis and prognosis of early cancer?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Are the PD(s)/PI(s) and collaborators appropriately trained in the areas of bioinformatics, imaging, data science, modeling and statistical, mathematical and computational biology? Will this team of investigators contribute unique skills to the overall EDRN Network? Are the PD(s)/PI(s) and support personnel adequately trained and qualified for participating and managing multi-institutional collaborations?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA: Will the proposed approaches be generally applicable to the development of biomarker validation study designs and statistical analysis of data related to the development of biomarkers and reagents? Are there adequate plans for effective interaction and coordination with the other Network units, 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

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: Is the infrastructure available to the applicants for data storage, data security and data analysis (imaging, modeling, data science, machine learning) appropriate to support the activities proposed? Has the applicant demonstrated adequacy of commitment and documented evidence of institutional support for proposed endeavor, and institutional support for computer services? Has the applicant demonstrated a sound management infrastructure for administering and monitoring the disbursement of the EDRN Core Fund?

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.

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.

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.

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.

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.

Not Applicable.

For Renewals, the committee will consider the progress made in the last funding period.

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.

Not Applicable.

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).

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).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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:

• 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.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH 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.

Awardees must comply with any funding restrictions described in Section IV.5. 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.

The award will include a restricted Network Core Fund that will be managed by DMCC awardee and approved by the NCI. The award will also include a restricted Network Collaborative Fund that will be used to support research collaboration between the awardee and other EDRN units as recommended by the EDRN Steering Committee and approved by the NCI.

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: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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. This includes ensuring programs are accessible to persons with limited English proficiency. 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 and http://www.hhs.gov/ocr/civilrights/understanding/section1557/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. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 75, and other HHS, 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 award 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 awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Oversee the DMCC activities to ensure that its areas of responsibility are fulfilled;
• Collaborate with other EDRN units to advance promising biomarkers towards EDRN validation studies;
• Accept and implement the goals, priorities, common protocols, procedures, and policies agreed upon by the Steering Committee for the individual and Network collaborative studies;
• Manage and monitor the disbursement of the EDRN Core Fund;
• Provide annual financial reports on the use of the Core Fund and any unobligated balance;
• Ensure Network and NCI review and approval of protocols, concepts, final protocol documents, informed consents, and study amendments, and advise NCI of changes in protocol status;
• Collaborate on common research designs or protocols, including methods and requirements for joint participation and collaboration as recommended by the Steering Committee, and handling of data, including appropriate sharing of methods and data among collaborating organizations;
• Define objectives and approaches, including the logistic support for the Steering and Executive Committees, organization of workshops, and provide assistance for other activities of the Network; and
• Participate in and be a voting member of the Steering Committee.
• In accordance with this cooperative agreement, the contact PD/PI together with at least one MPI or a senior investigator and an early-stage/junior investigator, will attend the Planning Meeting and two Steering Committee meetings in the first year, two Steering Committee meetings in each of the subsequent years of the award, and one EDRN-sponsored scientific workshop every 18 months (this usually coincides with one of the Steering Committee meetings).

As the number and types of Network validation studies will vary during the 5-year funding period, the number and identity of DMCC personnel should change in response to the scientific opportunities and expertise required, i.e. imaging, informatics, modeling, data science, etc. These changes must be approved by the NCI Project Coordinator. Qualified investigators in the DMCC should assume responsibility in a flexible manner as the need arises.

Recipients will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

PD(s)/PI(s) Responsibilities for Network Collaborative Studies:

• Collaborate with CVCs and BCCs to advance promising biomarkers towards EDRN validation studies;
• Accept and implement the goals, priorities, common protocols, procedures, and policies agreed upon by the Steering Committee for the individual and Network collaborative studies to the extent consistent with grant regulations;
• Ensure LIMS is extensible, Cloud-based and flexible to support the various EDRN studies, for which a collaborator with the necessary expertise may be appropriate;
• Ensure Network and NCI review and approval of study protocols, concepts, final protocol documents, informed consents, and study amendments, and advise NCI of changes in protocol status;
• Review the submitted information on specimen collections per the Network s CDEs and the registered study protocols;
• Collaborate on common research designs or protocols, including methods and requirements for joint participation and collaboration as recommended by the Steering Committee, and handling of data, including appropriate sharing of methods and data among collaborating organizations;
• Advise any collaborating investigators outside of EDRN that their institutions will also need to agree to be subject to the EDRN resource sharing and intellectual property requirements;
• Oversee the management of the EDRN Core Fund and the distribution of the subawards for activities recommended by the Steering Committee (via the Executive Committee) and approved for funds release by the NCI;
• Coordinate sIRB for approved EDRN 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 staff member serving as 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.

The specific roles of the substantially involved NCI staff members include the following activities:

• Coordinating and facilitating various activities of the EDRN program;
• Participating in the activities of the EDRN Steering Committee as voting and/or non-voting members;
• Serving as a liaison between the Steering Committee, the EDRN awardees, and the NIH;
• Ensuring that there are effective mechanisms to enable electronic communication among the Network units, and between the EDRN and the NCI. The NCI Project Coordinator will oversee this in coordination with the NCI CBIIT;
• Assisting the Steering Committee in developing and drafting Network operating policies and policies for dealing with recurring situations that require coordinated action;
• Facilitating collaborative research efforts that involve multiple EDRN awardees;
• Assisting the Steering Committee, the EDRN DMCC, and individual EDRN awardees in avoiding unwarranted duplications of effort across the EDRN;
• Assisting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs to disseminate results, tools, and models from the EDRN and take advantage of existing NIH/NCI resources and infrastructures;
• Co-organizing and participating in the EDRN-sponsored meetings;
• Monitoring the scientific progress of individual U01/U2C/U24 awards and the entire EDRN program;
• Reviewing the compliance of EDRN awardees with the recommendations developed by the Steering Committee;
• Coordinating external evaluation of the Network;
• Authorizing the use of funds from the EDRN Core Fund and individual set-aside funds for activities reviewed and recommended by the Steering Committee
• Conduct site visits shortly before completion of the third year of award to evaluate the progress made by the EDRN awardees. These will either a virtual or in-person site visit by Program staff and expert external consultants. A decision by NCI will be made at this time based on the comments from the site visit review team as to whether the overall goals of the center should be adjusted and/or modified for remaining period of the 5-year term.

The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to those Network recipient 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.

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.

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:

• All PD(s)/PI(s) representing each EDRN U01/U2C/U24 award; and
• The NCI-designated Project Coordinator.

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:

• Identifying scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH/NCI Program Officials for addressing such issues;
• Updating and refining established Network policies and procedures, including those for collaborative projects, protocols, and Network-defined projects;
• Updating and refining established policies and procedures at the request of specific EDRN centers for reviewing changes in projects not showing translational significance, and making recommendations to the NCI for replacing the project with more promising ones with revised scope and adjusted budget (increase in the budget will not be permitted);
• Updating and refining established standards or decision criteria for validating biomarkers/reagents for further clinical studies, such as testing early detection strategies, or as risk factors;
• Updating and refining established policies and procedures for accepting, reviewing, and recommending proposals from investigators outside the Network for supplemental funding and expanding the Network participation;
• Establishing a Data and Safety Monitoring Board for clinical trials, as appropriate, to ensure protection of human subjects;
• Reviewing patient accrual, follow-up, study protocol compliance, results of audits, and regulatory requirements at the participating EDRN centers and formally report the results of its reviews to the NCI;
• Promoting and fostering the inclusion of women and racial/ethnic minorities in clinical studies and assure the completeness of informed consent;
• Tracking the Network research progress and assuring that the results of laboratory research and clinical studies are published in peer-reviewed journals in a timely manner and in accordance with the publication policies of the Network;
• Planning one scientific workshop every 18 months during the Network project period to inform the scientific community and relevant patient advocacy groups of the progress made toward development and clinical application of biomarkers developed through the Network. The NCI Project Coordinator, members of the Network Consulting Team, and other NCI staff will provide the Steering Committee with advice on participants for the workshops. The DMCC will manage the logistics for these meetings;
• At any time during the course of a Network project (e.g., collaborative research supported by the Core Fund),the Steering Committee may ask a BCC or a CVC to serve the Network for developing clinical-grade assays on an as needed basis with appropriate compensation from the Core Fund. The Steering Committee may also examine the validation data for biomarkers/reagents developed by the Network, and decide when a biomarker is sufficiently validated, or recommend when to stop non-productive experiments relating to biomarkers validation;
• Discussing and authorizing the development of reagents or assay refinement through BCCs, CVCs, or the private sector;
• Reviewing (with assistance of external reviewers, as needed) and discussing collaborative projects/study protocols to be pursued with support of the EDRN Core Fund and individual set-aside funds. Data will be submitted centrally to the DMCC. The Steering Committee will define the rules regarding access to data and publications consistent with NCI policies;
• Advising NCI on activating funds for the recommended collaborative projects;
• Determining the lead investigators for Network-wide validation studies in consultation with the NCI;
• Discussing and authorizing collaborative projects to be pursued with support of the set-aside funds from individual U2C/U01/U24 awards;
• Reviewing progress of the EDRN toward meeting the overall Network goals;
• Ensuring that all EDRN members utilize the resources developed by the EDRN DMCC and JPL, as well as existing NCI and NIH resources and programs;
• Implementing the policy that the resource sharing and intellectual property requirements set forth for EDRN awardees are also adhered to by collaborating non-EDRN investigators and their institutions, including those involved in Core Fund supported activities (e.g., investigators/institutions participating in validation studies).

Network scientific, operational, and organizational policies and procedures, are also described in the EDRN Manual of Operations (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, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 75 Award Term and Conditions 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: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Sudhir Srivastava, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7028
Email: [email protected]

Guillermo Marquez, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7035
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected] (mailto:[email protected])

Amy R. Bartosch
Office of Grants Administration
National Cancer Institute (NCI), NIH
Telephone: 240-276-6375
Email: [email protected]

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.