Department of Health and Human Services

Part 1. Overview Information

Key Dates

Required Application Instructions

It is critical that applicants follow the 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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) is part of the Early Detection Research Network (EDRN) initiative. EDRN (https://edrn.nci.nih.gov/) is a national, integrated infrastructure for the development of biomarkers and the assembly of necessary resources. The goal of EDRN is the development, evaluation, and validation of biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer.

The purpose of this FOA is to solicit applications for the EDRN Data Management and Coordinating Center (DMCC). The proposed DMCC will be responsible for the following activities: 1) Network Coordination (coordination of Network-wide meetings and conferences), 2) Data Management and Study Protocol Development (statistical and computational analysis support, study design, informatics infrastructure), 3) Validation Study Infrastructure and Services (coordination and support of EDRN-sponsored biomarker validation studies), and 4) EDRN Core Fund Management. Prior affiliation with the EDRN is not required and all qualified investigators are invited to apply.

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

• Biomarker Developmental Laboratories (BDLs) (RFA-CA-14-014 U01), which will discover, develop, and characterize new or refine existing biomarkers and assays for risk assessment, detection, and molecular diagnosis and prognosis of early cancer;

• Clinical Validation Centers (CVCs) (RFA-CA-14-015 U01), which will conduct clinical research to validate biomarkers for risk assessment, detection, and the molecular diagnosis and prognosis of early cancer. CVCs will also serve as resource centers for collaborative research within the EDRN by participating in collaborative biomarker validation studies and collaborating with EDRN BDLs and BRL; and

• Biomarker Reference Laboratories (BRLs) (RFA-CA-14-016 U24), which will serve as a Network resource for clinical and laboratory validation of biomarkers, including assay development and refinement.

Biomarker Definition. In the context of this FOA, biomarkers are defined as cellular, biochemical, and/or molecular (including genetic and epigenetic) characteristics by which normal and/or abnormal biological processes can be recognized and/or monitored. Biomarkers are measurable in biological materials, such as in tissues, cells, and/or bodily fluids.

Background

EDRN Scientific Premise

Since its inception in 2000, the EDRN has followed a "vertical" approach to biomarker research that facilitates collaborations and hand-offs among technology developers, basic scientists, clinicians, epidemiologists, biostatisticians, and other health professionals. It also expedites efficacious clinical applications of the molecular knowledge that has burgeoned in recent years. The NCI anticipates 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 grantees and industry partners. Many EDRN investigators have or have had active collaborations with the industry. It is hoped that validated biomarkers may ultimately be commercialized into diagnostic products for early detection of cancer and cancer risk assessment. Structured around four main scientific units, the EDRN currently includes 20 BDLs, three BRLs, eight CVCs, and one DMCC.

EDRN Goals

The EDRN program is established to: (a) promote translational research to identify biomarkers for cancer risk, early detection, and molecular diagnosis and prognosis of early cancer; and (b) coordinate biomarker research within the extramural community and with other NCI programs in cancer prevention, screening, and treatment to reduce cancer morbidity and mortality (see EDRN Strategic Plan, http://edrn.nci.nih.gov). In the future, candidate biomarkers are likely to be discovered by Integromic approaches where genomics data will increasingly be integrated with other 'omic' data, such as proteomic, epigenomic, metabolomic, etc., to take advantage of the exponentially growing genomic knowledge of the cancer landscape.

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 early diagnosis and prognosis of cancer.

• Integrate biomarkers with imaging to reduce the false positive rate of imaging and to improve the detection of clinically significant cancers.

• Develop and validate biomarkers to improve the detection of cancer progression for patients on active surveillance.

• Develop assays for accelerating biomarker discovery and translation into the clinical area. This would include measures of diagnostic or predictive accuracy, sensitivity, specificity, and, whenever possible, clinical impact/benefits.

• Develop and implement diagnostic assays in support of the EDRN objectives by using multiple biomarkers, gene expression patterns, post-translational changes, epigenetic changes, and changes in metabolic profiles.

• Facilitate the development of high-throughput, sensitive assay methods to identify and implement biomarkers that are useful in assessing cancer risk, detecting early stage cancers, cancer diagnosis and prognosis.

• Support collaboration among academic and industrial leaders, whose areas of interest are in molecular biology/molecular genetics, clinical oncology, computer science, public health and/or other related areas, leading to the development of cancer diagnostics.

• Conduct clinical/epidemiological studies (e.g., cross-sectional, prospective, retrospective, etc.) in order to evaluate the predictive value of biomarkers.

• Continue to expand the informatics infrastructure to facilitate pre-competitive data 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 and cancer therapeutic trials.

These goals are achieved through a systematic, evidence-based discovery, development, and validation of biomarkers, based upon Standard Operating Procedures (SOPs) and Common Data Elements (CDEs) developed by the EDRN investigators and described in the EDRN Manual of Operations (http://edrn.nci.nih.gov/docs). The EDRN has established a five-phase approach as a standard and a roadmap for successfully translating research on biomarker applications from the laboratory to the bedside. The five phases for biomarker discovery and validation are:

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

The EDRN has also proposed a coherent and comprehensive set of guidelines for study design for the discovery and evaluation of biomarkers for early cancer detection, known as the prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) study design. 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 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 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 may be increased by inflammatory and other conditions present near the time of symptomatic diagnosis.

The articles on five-phase approach and PRoBE design are provided on the EDRN website (http://edrn.nci.nih.gov/docs).

EDRN Administrative Structure (For Information Only)

EDRN will be structured around the four main scientific units, funded through separate FOAs, to include approximately 12-16 BDLs, 4-5 BRLs, 8-9 CVCs, and one DMCC. Although individual teams of EDRN awardees (BDLs, BRLs, 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 representative PD/PI of BRLs, the NCI Project Coordinator, and the Chairs of the EDRN Collaborative Groups. The latter are based on organ site and EDRN PIs can be members of one or more Collaborative Groups.

Assisted by the Executive Committee and NCI Program staff, duties of the Chair of the Steering Committee include:

• Preside at all meetings of the Steering Committee;
• Appoint and re-appoint members of Subcommittees, Review Groups, and designate special assignments;
• Appoint ad hoc committees as needed;
• Invite consultants as needed to Subcommittees, etc.;
• Appoint EDRN liaison members to other organizations;
• Serve as an ex-officio member of all Subcommittees, ad hoc Committees, and Task Forces;
• Submit annual EDRN Progress Reports to NCI and the Network Consulting Team.

Further details of Steering Committee composition and responsibilities are provided in Section VI.2. Administrative and National Policy Requirements: Cooperative Agreement Terms and Conditions.

Headquarters: The institution of the Chair of the Steering Committee serves as the Headquarters of the EDRN. The Headquarters serve as a center for dissemination of information to investigators and institutions in EDRN, as well as to those outside the Network. The Chair serves as the PD/PI of the Headquarters and oversees the implementation of the scientific, operational, and organizational policies of the Network.

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 non-EDRN investigators. Since the Core Fund is restricted and reserved for post-award activities, no requests for Core Fund support can be made in the application in response to this FOA.

The management of the EDRN Core Fund will be a responsibility of the 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 distribute the approved funds under appropriate sub-award agreements.

In the past, $2-5 million was allotted to the Core Fund and was contingent upon the availability of funds. In the new EDRN funding cycle, it is anticipated that a similar amount will be set aside for the Core Fund.

Network Consulting Team: The Network Consulting Team is composed of a Chair and non-EDRN members appointed by NCI. The Network Consulting Team reviews the progress of the EDRN, recommends new research initiatives, and ensures that the Network is responsive to promising opportunities in early detection research and risk assessment. The Network Consulting Team can recommend new research projects to the Steering Committee or to NCI. Members of the Network Consulting Team can serve on ad hoc Committees of the EDRN, internal Review Groups, and as consultants to subcommittees.

Specific Responsibilities and Requirements

Scope. This FOA encourages the submission of applications to establish and enhance the EDRN DMCC. The DMCC must have expertise and capabilities in biostatistics, information technology and bioinformatics support, data management, protocol development, and in coordinating and providing logistical support for meetings and conferences. It is essential that the DMCC applicants familiarize themselves with the companion FOAs for the other EDRN units with which the DMCC must work: BDLs (RFA-CA-14-014 U01), CVCs (RFA-CA-14-015 U01), and BRLs (RFA-CA-14-016 U24).

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;
• Enhance and conduct management of data and protocol development, e.g., enhance and maintain the Validation Study Information Management System (VSIMS). This is a Laboratory Information Management System (LIMS), which provides a comprehensive array of support services including study development, documentation of CDEs, development and distribution of reference sets, data entry checks, study-specific reports, specimen tracking, monitoring and selection, eligibility programming and ongoing remote study staff support and data harmonization;
• Enhance and maintain informatics and infrastructure services for biomarker development (e.g., EDRN Knowledge Environment (EKE), Distributed Specimen Locator System (aka, EDRN Resource Network Exchange; ERNE), 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 at NASA's Jet Propulsion Laboratory (JPL);

• Enhance and maintain Network integration and coordination;

• Provide logistical and administrative assistance in arranging Network-wide meetings and workshops;

• Manage the EDRN Core Fund.

Note: NCI will hold a pre-application informational webinar for this FOA. Date, time, and other details will be posted at http://edrn.nci.nih.gov/.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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

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

Foreign Institutions

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.

Required Registrations

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) (formerly CCR) 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.
• 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

A proposed PD/PI may not serve as a contact PD/PI on more than one application submitted in response to this FOA.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• 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.
Chief, Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute
9609 Medical Center Drive, Room 5E136, MSC 9790
Bethesda, MD 20892-9790 (for USPS Regular or Express delivery)
Rockville, MD 20850 (for non-USPS delivery)
Telephone: 240-276-7028
Fax: 240-276-7845
Email: [email protected]

Page Limitations

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.

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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 a 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 validation studies.

SF424(R&R) Senior/Key Person Profile

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 and technologies for cancer detection.

R&R Budget

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 $2 million per year (direct costs) may be allocated to the activities of DMCC. The reminder (of up to $2.5 million) 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 1.8 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 to their respective projects.

c) Network Core Fund: Applicants should include up to $2.5 million in direct costs for the restricted Network Core Fund in the budget request. 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 operation (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 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.

c) Restricted Travel Expenses Budget: Applicants must budget for travel and per diem expenses for EDRN meetings and workshops. In the first year, applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PDs/PIs option is not used) to attend a Planning Meeting and two Steering Committee meetings. In the second and subsequent years, applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PDs/PIs option is not used) to attend two Steering Committee meetings per year and an EDRN 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 one Steering Committee meeting, one Network Consulting Team meeting, 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;

2) Informatics Services:

• Maintain and develop secure website to allow for communication among EDRN members and posting of study results;
• Develop tools for biomarker validation in collaboration with JPL;
• 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).

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

Sub-section A: Overview

Outline the advantages of the proposed DMCC to serve as a scientific and organizational hub to the entire Network. In this overview, explain the anticipated significance and 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. These highlights should include (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, etc.);

• Rigorous study design and development of study protocols applicable to multi-center collaborative studies (including robust data collection and quality control procedures); and

• Efficiency 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 how the team's strengths in biostatistics, data management, data analysis, and project management skills have been used in previous, successful large-scale collaborative research;

• 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 previous large-scale, complex research projects;

• Describe how logistical services and organizational support have been utilized in managing resources and monitoring performance in previous large-scale, collaborative research.

Sub-section B: Previous Accomplishments

Relevant Recent Accomplishments (all applications): Applicants must describe previous research accomplishments/preliminary studies relevant to biomarker development and the goals of the proposed DMCC. The description should address (but is not limited to) the following aspects:

• Implementation of statistical and computational tools in biomarker development 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 applications only). Include additional information in this section summarizing the current 5-year funding period and include the following items (a-c):

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.

c) Provide a synopsis of the review from the latest site visit by external reviewers and describe steps taken to address any concerns in this review.

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 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, if needed, 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.

1. Network Coordination

• 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;

• Provide other operational support for the Network (e.g., communications, subcommittee meetings, teleconferences);

• Produce and maintain all documents, including Manual of Operations and procedure manuals;

• Contribute to the development 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 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 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;

• 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 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;

• 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.

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 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, VSIMS, 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. DMCC will work closely with EDRN IC 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, coordination of Network-wide meetings, 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.

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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide with the following modifications.

• 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). 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

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

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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete and/or non-responsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

In addition, 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

In addition, specific to this FOA: Are the PD(s)/PI(s) and collaborators appropriately trained in the area of 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?

Innovation

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

In addition, 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 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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?

In addition, specific to this FOA: Is the infrastructure available to the applicants for data storage, data security and data analysis 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?

Additional Review Criteria

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the current funding period. The following aspects will be evaluated:

Did the incumbent DMCC successfully carry out their responsibilities for 1) Network Coordination; 2) Data Management and Study Protocol Development; and 3) Validation Information System and Services? Did the team actively participate in EDRN activities? Were significant contributions made towards meeting the EDRN goals?

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS)

Intellectual Property Management Plan: Reviewers will comment, as appropriate, on the adequacy and feasibility of the sharing of research resources plan and the Intellectual Property Management Plan (IPMP). Comments on the plans and any concerns will be presented in an administrative note in the Summary Statement. NCI Program staff will consider the adequacy of the plans in determining whether to recommend an application for award.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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 on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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. This aspect will include the adequacy of the Intellectual Property Management Plan.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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 grantee’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.

2. Administrative and National Policy Requirements

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 awardees 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 awardees 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 semi-annual financial reports on the use of the Core Fund;

• 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 PD/PI together with an additional senior investigator (or two PD(s)/PI(s) for multi-PD/PI awards), will attend a 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. 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.

Awardees 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 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 to the extent consistent with grant regulations;
• 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; and

• 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 sub-awards for activities recommended by the Steering Committee (via the Executive Committee) and approved for funds release by the NCI.

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.

Main NCI responsibilities include the following:

• Coordinating and facilitating various activities of the EDRN program;
• Participating in the activities of the EDRN Steering Committee;
• 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 operating policies and policies for dealing with recurring situations that require coordinated action;
• Assisting the investigators in avoiding unwarranted duplications of effort across the Network;
• Co-organizing and participating in the EDRN-sponsored meetings;
• Monitoring the scientific progress of individual U01/U24 awards and the entire EDRN program;
• Reviewing the compliance of EDRN awardees with the recommendations developed by the Steering Committee; and 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.

The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to those Network awardee institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.

Additionally, 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. Program Officials may also have substantial programmatic involvement (as Project Scientists).

Areas of Joint Responsibility Include:

Steering Committee: 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/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 NIH staff) will be selected by the Steering Committee. The awardee institution represented by the Chair of the Steering Committee will serve as the Headquarters (for definition, see Section I. Funding Opportunity Description. EDRN Administrative Structure).

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 Scientists/Coordinators will serve on such subcommittees, as they deem appropriate.

Primary responsibilities of the Steering Committee include, but are not limited to, the following activities:

• Updating and refining established Network policies and procedures;
• Updating and refining established policies and procedures for collaborative projects, protocols, and Network-defined projects;
• Updating and refining established policies and procedures for reviewing changes in projects not showing translational significance at the request of the laboratories/centers, 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 Committee for clinical trials as appropriate to ensure protection of human subjects;
• Reviewing patient accrual, follow-up, protocol compliance, results of audits, and regulatory requirements at the participating Centers and formally report the results of its reviews to the NCI;
• Promoting and fostering the inclusion of women and 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 Workshop every 18 months during the Network project period to inform the scientific community and relevant 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 BDL or CVC to serve as a BRL 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 BRLs, CVCs, or the private sector.
• Approving collaborative studies/protocols. 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.
• Determining the lead investigators of 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 U01/U24 awards.

• Reviewing (with assistance of external reviewers, as needed) and discussing collaborative projects to be pursued with support of the EDRN Core Fund and individual set-aside funds.

• Advising NCI on activating funds for the recommended collaborative projects.

• 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).

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

Approved Resource Sharing and Intellectual Property plans will become a condition of the grant award and Progress Reports must contain information on activities for the sharing of research resources and intellectual property.

A final progress report, 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.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

Scientific/Research Contact(s)

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

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]

Section VIII. Other Information

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.

Authority and Regulations

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 Parts 74 and 92.