NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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

This Funding Opportunity Announcement (FOA) solicits applications for Research Centers for Barrett’s Esophagus Translational Research Network (BETRNet). The BETRNet is an NCI program established to address the rising incidence of esophageal adenocarcinoma (EA) in the United States and to energize the field of EA research. Specifically, the program seeks a better understanding of the biology of EA and its precursor lesion, Barrett’s esophagus (BE), as the foundation for developing preventive measures that would improve patient management. The BETRNet will be comprised of the following units:

• Three to four multi-institutional, trans-disciplinary Research Centers (to be supported by this FOA);
• One Coordinating Center (to be supported by a companion FOA, RFA-CA-16-007).

The Research Centers will serve as the scientific platform of the BETRNet Program. Each Center will encompass a multi-institutional, trans-disciplinary group with basic, clinical, and computational research expertise. Each Center will be supported by critical cores and strong organizational oversight to enable the investigation of novel research questions, development of important resources and models, and outreach to the larger scientific community.

The Research Centers will be assisted by the BETRNet Coordinating Center in terms of network interactions and collaborations, participation in the patient registry-virtual biorepository, and participation in cross-BETRNet pilot projects. Through these collaborative efforts, BETRNet can accelerate the integration and translation of important research findings generated from individual laboratory- and clinically-based studies into applications for EA prevention.

Esophageal adenocarcinoma is a highly lethal malignancy that had risen in incidence more than 600% in the United States in the previous four decades. The incidence and incidence-based mortality of EA continue to increase, with five-year survival of 16% and median survival of less than one year. Notwithstanding an identified precursor lesion, BE, that increases individual risk by 11-30-fold, it became apparent that better characterization of EA pathogenesis as well as new biologically-based strategies for EA prevention and detection are greatly needed to decrease the impact of this deadly cancer.

Research on the biology of EA has revealed various molecular and cellular events associated with malignant transformation in the esophagus. However, the significance of these events for esophageal cell transition and their utility for EA early detection, risk prediction, or prevention have not been demonstrated. Systematic investigations in rare cancers require focused and coordinated efforts with access to resources including in vivo and in vitro models that replicate the human disease, as well as sufficient numbers of annotated human specimens and clinical cohorts for prospective screening, detection and preventive intervention studies. In the past, inadequate access to these resources has limited the capabilities of individual investigators, in both basic and clinical research. Accordingly, the BETRNet Research Centers are designed to foster trans-disciplinary collaborations within each Research Center and across the Centers to enable a deeper understanding of EA biology, provide strategies for EA prevention, and better define individuals at risk. The ultimate goal is to decrease the incidence, morbidity and mortality of EA.

All proposed BETRNet Research Centers must include the following main attributes (for additional details on the requirements, please see Section IV Application and Submission Information):

(A) Overall Research Focus. Each proposed Research Center must represent a multi-disciplinary translational research program that can align with the scientific areas defined in this FOA. The Center program must focus on timely progress towards the specific objectives described in this FOA (i.e., better understanding of the biology of EA and its precursor lesion, BE, as the foundation for validated preventive measures that would improve patient management). The potential impact and subsequent pathways for future translation of the outcomes of each research project and the Center program as a whole must be well articulated. Applications that are not within the scope of this FOA will be considered non-responsive. (Non-responsive applications will not be reviewed.)

(B) Research Team. Each team must represent an appropriately diversified research group as needed to achieve the goals of the proposed Research Center. Each team must have the full expertise and capabilities for the proposed Research Center and the involvement of multiple institutions is encouraged. The team members must be willing and able to work jointly and across the scientific disciplines to ensure the successful conduct and completion of the proposed studies.

(C) Research Projects. Each proposed Research Center must include a minimum of 2 interrelated and defined research projects from one or more of the research areas listed below. A third research project consistent with the theme of the application may also be proposed by the applicants. These projects are expected to be interactive and synergistic, collectively supporting the overarching goal of the Research Center and reflecting a trans-disciplinary research program.

Possible Research Areas for the Required 2 Research Projects

• The biology and development of esophageal stem cells and whether they are slow dividing cells or proliferative progenitors;
• Mechanisms and effectors that direct the proliferation and expansion of esophageal stem cells and their contribution to BE and EA;
• The effects of acid and inflammation on the function of esophageal stem cells;
• The role of non-esophageal stem cells in the development of BE and EA;
• Construction of the comprehensive signal transduction systems that mediate the evolution of BE and EA, both within the tumor and through the tumor microenvironment;
• Effects of spatial distribution of genetic alterations in BE on the evolution of EA;
• The genomics of tumor heterogeneity and tumor plasticity and their impact on the progression toward EA;
• The genomics of obesity in relation to the risk of developing EA and/or to inform molecular targeting for cancer preventive interventions;
• Molecular mechanisms mediating the effect of abdominal obesity on the development of BE and EA and to inform cancer preventive interventions;
• Alterations in the BE and EA microbiota, the role of the microbiota in BE-EA transition and its possible modulation for cancer prevention;
• Biological processes that explain the male female disparity in BE and EA prevalence;
• Biological processes that explain the racial disparity between whites and African Americans in BE and EA prevalence;
• Targeting biological processes (e.g., inflammation) with cancer preventive agents to prevent EA
• Development of immunoprevention approaches for EA;
• Biology of ablative therapies and the post ablation esophagus, mechanisms of BE recurrence and risk of EA; and/or
• Development of models, such as genetically engineered mice, patient-derived xenografts (PDX) models, cell lines, and/or organoid cultures that would provide dynamic platforms for understanding and targeting the transformation of esophageal epithelium in human.

(D) Leadership and Organization of the Research Center. Given the multi-disciplinary and multi-institutional Research Centers to be proposed, their laboratories, research facilities, and administration are likely to be distributed across the geographical sites of the participating institutions. To efficiently manage and coordinate interactions across these sites, each proposed Research Center must include an Administrative Core to facilitate project management, communications, and results dissemination within the Center as well as coordination of activities with the BETRNet Coordinating Center.

(E) Patient Registry-Virtual Biorepository. Each Research Center must include a Patient Registry-Virtual Biorepository Core to support specimens' collection for the Center's translational research projects as well as the centralized BETRNet program's virtual repository that will be located at the BETRNet Coordinating Center. The Core must have the capabilities for timely sharing of specimen data with the BETRNet Coordinating Center for trans-BETRNet specimen management.

(F) Pilot Projects. Each BETRNet Research Center must solicit and support Pilot Projects (to be conducted within the Research Center and/or the Center's collaborators) and participate in cross-BETRNet projects. As both types of projects will be approved later in the program, no such projects should be proposed in the Center application. However, investigators are expected to incorporate their overall strategies for soliciting such projects as flexible means for exploiting emerging scientific opportunities.

An important aspect of the BETRNet collaborative network is the establishment of the centralized multi-institutional Patient Registry-Virtual Biorepository that will be coordinated and managed by the BETRNet Coordinating Center. The repository will contain clinical, demographic, and molecular data sets associated with biospecimens collected and available at each participating Research Center. The cohort of patients will include individuals at all levels of risk for BE and EA as well as controls, thus providing opportunities for understanding the biology of EA and determining molecular risk stratification criteria. A goal of the patient registry virtual biorepository is to function as a centralized shared resource for the entire program to advance research in this area. All BETRNet Research Centers will be required to participate in this resource.

The BETRNet (i.e., Research Centers and Coordinating Center) will be governed by the BETRNet Steering Committee. Details on the composition and functions of BETRNet Steering Committee are provided in Section VI.2, Administrative and National Policy Requirements, Cooperative Agreement Terms and Conditions.

BETRNet Research Centers will be expected to participate in performance evaluation activities during the term of the program. The purpose of this endeavor (to be coordinated by the BETRNet Steering Committee Chair) will be to monitor progress and provide feedback to individual Research Centers. Such feedback will facilitate optimization of various aspects of the program and implementation of corrective actions if needed. The overriding goal will focus on identifying approaches to conduct highly collaborative, trans-disciplinary translational research that could not be achieved by individual investigators working separately and, thereby, increasing the likelihood for significant scientific advances.

BETRNet awardees will be expected to participate in an external evaluation process that will be coordinated by the NCI Scientific staff. This evaluation will largely be based on the overall progress towards achieving the scientific goals of the entire BETRNet Program. The evaluation will assess the quality and innovation of the research conducted by BETRNet, progress of the research projects, effectiveness of the collaborative pilot projects, and critical antecedents and intermediate determinants of the overall success. Specific aspects may include: peer-reviewed publications, achievement of planned milestones, development of infrastructure and research capacity, efficiency of resource utilization, and data sharing arrangements as appropriate within and among BETRNet Research Centers. Particular focus areas will be on improved understanding of EA carcinogenesis, and the development of EA preventive modalities that are based on the underlying biological mechanisms of the disease.

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 in response to 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:

• 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
• County 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) (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.

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.

Given the required multi-disciplinary and multi-institutional teams, applicants are encouraged to take advantage of the multiple PDs/PIs option.

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

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).

An applicant institution may submit more than one Research Center application in response to this FOA provided that these applications correspond to different PDs/PIs and different key persons.

Applicants can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

Although a letter of intent 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:

• Number and title of this FOA
• Title of the proposed U54 Research Center
• A paragraph describing the proposed research activity
• Name(s), address(s), telephone number(s), and email(s) of the Principal Investigator(s)
• Name(s) of the participating institution(s)

The letter of intent should be sent to:

Rihab Yassin, Ph.D.
National Cancer Institute
Telephone: 240-276-6230
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (Use for Administrative Core)	6
Project (Use for Research Projects)	12
Core A (Use for Patients Registry-Virtual Biorepository Core)	6
Core B (Use for Pilot Projects Core)	6
Core (Use for Other Shared Resource Core)	6

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Research Projects: 2 required, maximum 3 allowed
• Patients Registry-Virtual Biorepository Core: required
• Pilot Projects Core: required
• Other Shared Resource Core: optional, only 1 allowed

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application. When multiple PDs/PIs are proposed, NIH requires that one PD/PI be designated as the contact PD/PI for all communications between the PDs/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs. but has no special roles or responsibilities within the project team beyond those mentioned above.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Describe the overall specific aims of the proposed BETRNet Research Center and its scientific focus.

Research Strategy: Provide an overview of the proposed Research Center. Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section A) Research Center Framework. Describe the overarching organizational framework and vision of the proposed Research Center, its scientific focus, strengths, and leadership in the research field;

Sub-section B) Research Team. Summarize the major collective strength of the research team in the proposed area of research. Without repeating information from individual biosketches, explain how the specific expertise of team members (e.g., cancer biology, genomics, molecular medicine, computational biology, bioinformatics, others) will be used to advance the proposed research program; describe the environments (e.g., academic or other research) of the research team members and how theywill support the mission of the proposed Research Center;

Sub-section C) Individual Research Projects. Outline the rationale for the proposed research projects, their innovative thinking, and reasons for their inclusions. Two research projects must be proposed based on one or more of the scientific areas listed in Section I, under "Key Requirements for BETRNet Research Centers". A third research project can be proposed by the applicants as appropriate to the theme of the application;

Sub-section D) Center Integration. Describe how the Center and the investigators team will collectively support the overarching goal of the Center through multi-disciplinary and multi-institutional collaborations. Also describe how the Center will support innovatively the overall vision of the BETRNet program in deciphering the biology of EA and translating knowledge into management and prevention measures;

Sub-section E) Future Directions. Describe the overall foresight of the Center (beyond the BETRNet award) for advancing research on EA.

Letters of Support: Include a letter of support from an institution official endorsing the proposed BETRNet Research Center and describing available institutional resources to support the Center research. Also include letters from investigators who will serve as consultants or collaborators on the project but with no measurable efforts. Do not include letters from investigators who will have committed efforts in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Resource Sharing Plan should be provided only under the Overall component but it should cover all the activities proposed for the BETRNet Research Center.
• Specimens Sharing: All BETRNet awardees will be expected to provide information about the availability of biospecimens at their institutions as well as associated clinical/demographic information to the patient registry-virtual biorepository created and maintained by the BETRNet Coordinating Center, consistent with achieving goals of the program. All BETRNet applicants are expected to be willing to share biospecimens and related information with other BETRNet investigators pursuant to the terms of the informed consent. In line with these, BETRNet awardees will be expected to structure the informed consent document with considerations for the wider sharing of data and specimens collected under the BETRNet 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.

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

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Leader and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The contact PD/PI of the BETRNet Research Center should serve as the Administrative Core Leader.
• A qualified Core administrator should also be appointed to manage the daily activities of the BETRNet Research Center. In the additional Senior/Key section, provide the role under 'Other Project Role Category' as 'Core Administrator'.
• A senior statistician should be included in this Core to provide statistical support for the Research Center. In the additional Senior/Key section, provide the role under 'Other Project Role Category' as 'Statistician'.

Budget forms appropriate for the specific component will be included in the application package. The budget should account for the efforts of the Core Leader, Core Administrator, Statistician, and other Key Persons. The budget should also include travel funds for the PD(s)/PI(s) to attend the annual BETRNet Steering Committee meeting and participate in other network related activities.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the goals of the Administrative Core.

Research Strategy: Address the specific aspects indicated below using the sub-sections as defined:

Sub-section A) Core Structure. Outline the organization and function of the Administrative Core. Incorporate the plans for specific administrative activities of the Research Center including, but not limited to, progress reports, monthly meetings and teleconferences, development of a Center advisory group, travel for the PD(s)/PI(s) and team leaders to scientific meetings, and other activities. Describe the plans for coordination and communication with the BETRNet Coordinating Center and NCI scientific staff. Finally, describe the plans for participation in the BETRNet Steering Committee and in cross-BETRNet activities.

Sub-section B) Leadership and Center Organization. Outline the organization of the leadership structure and overall Center structure (provide respective organizational diagrams). Describe the the lines of responsibility.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application GuideResource Sharing Plans should only be provided in the Overall component of the application.

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.

PHS Inclusion Enrollment Report (Administrative Core)

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

When preparing your application in ASSIST, use Component Type 'Project.'

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project, starting with "Required Project 1:" or Required Project 2:" or "Optional Project:".
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Leader and provide a valid eRA Commons ID in the Credential field;
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component;
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component;
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Projects)

Budget forms appropriate for each individual research project should be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Specific Aims: Describe the goals of the proposed research project.

Research Strategy:

Statement of Research Area(s) Relevance. If a given Research Project is one of two required projects, include at the beginning of Research Strategy a statement identifying which of the possible research areas (listed in Section I) is/are being addressed by a given project. For an optional research project, indicate how that project connects to research area(s) of the required projects.

Use the standard subsections of Research Strategy defined in the SF424 Application Guide (Significance, Innovation, and Approach) to describe the Research Strategy. Emphasis should be placed on demonstrating why the proposed concepts and approaches are innovative within the context of related research and how the expected outcomes will overcome current knowledge gaps and barriers to clinical management of EA. In appropriate sub-sections, address the integration in and contribution of the research project to the overall Research Center program and explain why a given project is essential for achieving the Center's overarching goals.

Resource Sharing Plan: Resource Sharing Plans should only be provided in the Overall component of the application.

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.

PHS Inclusion Enrollment Report (Administrative Core)

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

When preparing your application in ASSIST, use Component Type Core A.

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

SF424 (R&R) Cover (Patients Registry-Virtual Biorepository Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Patients Registry-Virtual Biorepository Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Patients Registry-Virtual Biorepository Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Application guide states that Project Narrative is required. However it is only required for the Overall component. If you would like the applicant to provide a project narrative for this component, update the above instructions accordingly. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

Project /Performance Site Location(s) (Patients Registry-Virtual Biorepository Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Patients Registry-Virtual Biorepository Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Leader and provide a valid eRA Commons ID in the Credential field;
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component;
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component;
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Patients Registry-Virtual Biorepository Core)

Budget forms appropriate for the specific component will be included in the application package.

In the budget include:

• The costs for centralized specimen data collections and archive to the BETRNet Coordinating Center; and
• The cost for new specimens' collection that will support and expand the centralized BETRNet Patients Registry-Virtual Biorepository.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Patients Registry-Virtual Biorepository Core)

Specific Aims: Describe the goals of the Patients Registry-Virtual Biorepository Core.

Research Strategy: Address the following aspects using the sub-sections as defined:

Sub-section A) Outline of the Core and its Collections. Describe the collections of human specimens and associated data at all the participating sites in the BETRNet Research Center and whether the specimens are available for collaborative research studies with BETRNet as well as outside investigators. Also include in this section a description of any unique human cell lines/organoid collections available at the Center to support BETRNet research;

Sub-section B) The Bioinformatics Capabilities of the Core. Describe the infrastructure and resources available at the core to support timely release of specimen data and their submission for centralized data collection at the BETRNet Coordinating Center;

Sub-section C) Support for the Center Projects. Describe the role of the Core in facilitating the projects of the Research Center as well as collaborations with other BETRNet Research Centers.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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.

PHS Inclusion Enrollment Report (Patients Registry-Virtual Biorepository Core)

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

When preparing your application in ASSIST, use Component Type Core B.

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

SF424 (R&R) Cover (Pilot Projects Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Pilot Projects Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Pilot Projects Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Application guide states that Project Narrative is required. However it is only required for the Overall component. If you would like the applicant to provide a project narrative for this component, update the above instructions accordingly. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

Project /Performance Site Location(s) (Pilot Projects Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Pilot Projects Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Leader and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Pilot Projects Core)

Budget forms appropriate for the specific component will be included in the application package.

The budget request should account for the efforts of the Core Leader and other Key Persons and staff. The budget should also include funds to be allocated by each Center specifically for pilot studies in the amount of $110,000 in direct costs per year, starting in year 2 of the program. The funds include $40,000 in direct costs per year for within Center pilots and $70,000 in direct costs per year for Cross-BETRNet pilots. The release of these restricted pilot funds will be recommended by the BETRNet Steering Committee and approved by NCI scientific staff, respectively.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Pilot Projects Core)

Specific Aims: Describe the goals of the pilot projects Core.

Research Strategy: Describe the specific aspects indicated below using the sub-sections as defined:

Sub-section A) Pilot Development and Evaluation. Outline the Research Center's overarching vision for development of Pilot Projects and cross-BETRNet Projects and their respective evaluations. Outline the mechanisms that will be employed by the Center for soliciting and prioritizing ideas for these projects. Include key scientific capabilities, which the applicant Center can provide to support such projects. As specific Pilot Projects or cross-BETRNet Projects will be developed and selected post-award, no such specific projects should be listed in the application;

Sub-section B) Outreach Activities. Outline the Center's plans for outreach interactions to bring in expertise from outside the individual Research Center that will enhance specific pilots. Outline the Center's vision for any other activities that could have a synergistic effect on the outcomes of the BETRNet Program. Also describe how the proposed Center may interact with other non-BETRNet entities to increase the impact of BETRNet research.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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.

PHS Inclusion Enrollment Report (Pilot Project Core)

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

Other Shared Resource Core is optional. When preparing your application in ASSIST, use Component Type 'Core'.

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

SF424 (R&R) Cover (Other Shared Resource Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of the Core (Start the title with "Optional")
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Other Shared Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Other Shared Resource Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Application guide states that Project Narrative is required. However it is only required for the Overall component. If you would like the applicant to provide a project narrative for this component, update the above instructions accordingly. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

Project /Performance Site Location(s) (Other Shared Resource Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Other Shared Resource Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Leader and provide a valid eRA Commons ID in the Credential field;
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component;
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component;
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Other Shared Resource Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Other Shared Resource Core)

Specific Aims: Describe the goals of the Shared Resource Core. Indicated which specific Research Projects will be served by this Core

Research Strategy: The Shared Resource Core is expected to support two or more Research Projects. Any additional services, support, and/or resources to be provided to other Research Center components (if applicable) should be clearly defined.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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.

PHS Inclusion Enrollment Report (Other Shared Resources Core)

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

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) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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.

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 (SAM). 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-13-030.

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.

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire BETRNet Center (Overall component) and for each individual Research Project. In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria and for the Research Projects criteria, but not for the other components.

All other components of the Center [i.e., Administrative Core, Patients Registry-Virtual Biorepository Core, Pilot Projects Core, and optional Other Shared Resource Core] will be evaluated but each will receive only one overall adjectival (not numerical) score.

For the evaluation of the BETRNet Research Center application, the Research Projects will be emphasized as the scientific base of each Center, with additional components enhancing and integrating the overall research/outreach program.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the BETRNet Research Center 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 Center 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 Research Center that by its nature is not innovative may be essential to advance a field.

Does the Research Center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the Center 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 for this FOA: Are the organizational framework, vision, and scientific focus of the proposed Research Center designed to enable a unique understanding of the biology of EA development that can inform effective approaches to risk stratification, prevention and early detection? Is the requirement for the Research Center structure to accomplish the proposed goals of the program well-articulated? Are the proposed concepts and approaches innovative within the context of related research such that the results could close current knowledge gaps and overcome barriers to clinical management of non-invasive EA (e.g., strategies that identify individuals (among those with and without known BE) who are most likely to develop EA and/or to interfere with invasive EA formation)? Are the Center components and the investigators team well integrated to collectively support the overarching goal of the Center and the vision of the BETRNet program?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Research Center? 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?

Specific for this FOA: Are the backgrounds, expertise, and commitments of the PD(s)/PI(s) and other key persons sufficient for the proposed scope of activities and in line with the overall goals of the BETRNet? For applications involving multiple PDs/PIs, are their designated roles and responsibilities well defined, adequate, and complementary for achieving the goals of the proposed Research Center? How well do the proposed collaborations between the Research Center’s PD(s)/PI(s) and other key persons integrate the Center structure to achieve its overarching research goals?

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?

Specific for this FOA: Does the proposed Research Center employ novel concepts, approaches, and/or methods to understand EA formation and/or identify or prevent EA risk? Are the Center's goals original and innovative? Does the Center challenge existing scientific paradigms or develop new concepts, methodologies, and/or technologies?

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

If the Research Center 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?

Specific for this FOA: How well does the proposed Research Center take advantage of transdisciplinary approaches to promote and advance the understanding of the mechanisms and behaviors underlying EA, from biology to prevention? Are the overall research goals, experimental design, methods, and capabilities sound and well developed? Are effective mechanisms in place to foster strong collaborative interactions and promote cross-fertilization among investigators and participating institutions? Are mechanisms for facilitating sharing of samples and resources well planned or in place as appropriate and consistent with achieving the goals of this program?

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 for this FOA: Will the scientific environment at the participating institutions stimulate trans-disciplinary research collaborations?

Organizational Framework and Integration

How well will the proposed Research Center take advantage of the infrastructure for BETRNet and existing resources at the participating institutions? Will the Center be able to effectively coordinate the efforts of its participating institutions as well as coordinate with the entire BETRNet program? Does the Center have the capacity and budgeted resources to effectively work with the BETRNet Coordinating Center? Is there evidence of sufficient institutional support for the proposed Research Center across the participating institutions? Is there evidence of ongoing productive interactions among participating investigators/institutions? Will the proposed Cores enhance the capabilities of Center program?

As applicable for the Research Center 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 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.

When the proposed Research Center 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.

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 on the goals proposed in the initial Research Center application.

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 .

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.

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

Significance

Does the proposed research project address an important problem related to EA biology with potential for translation into prevention strategies? If the aims and milestones of the project are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods in the field and on the management and prevention of EA?

Investigators

Are the investigators appropriately trained and well suited to carry out this work? Is the project proposed appropriate to the experience and expertise of the project leader and other researchers and team members?

Innovation

Does the proposed project employ novel concepts, approaches, and/or methods to solve the problem stated in the study? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies, theories, and/or technologies?

Approach

Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternatives, as appropriate?

Environment

Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments benefit from unique features of the scientific environment or employ useful collaborative arrangements?

Reviewers will provide only one overall adjectival impact score for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

As described for the Administrative Core, is there adequate evidence for the managerial and collaborative capabilities of the proposed leadership? How appropriate is the leadership structure and activities of the proposed Research Center in terms of facilitating: (a) achievement of the overall goals of the Research Center; (b) integration of multiple institutions participating in a given Research Center; and (c) collaboration in cross-BETRNet activities?

Reviewers will provide only one overall adjectival impact score for the Patient Registry-Virtual Biorepository Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

How well is this Core integrated in the proposed Research Center? Can the Core allow the proposed Research Center, as a whole, to be responsive to the scientific challenge of acquiring an adequate number of human samples to appropriately test the stated hypotheses? How well can the available Core infrastructures integrate with the BETRNet Coordinating Center?

Does the Center outline its intent to collaborate and share specimens and cell models within the Center investigators and across the BETRNet program as appropriate and consistent with achieving the goals of the program? Does the investigative team either jointly or individually have access to existing and prospectively collected biospecimens?

Reviewers will provide only one overall adjectival impact score for the Pilot Project Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

Are the plans for proposing, identifying, and formulating pilot projects adequately described and appropriate for the goals of the Research Center? Are the plans for participation in the cross-BETRNet projects adequately described and appropriate for the goals of BETRNet? Are the conceptual frameworks adequately developed, well integrated, and appropriate?

Reviewers will provide only one overall adjectival impact score for the optional Shared Resources Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

How well matched is the proposed Shared Resource Core to the needs of the overall Research Center? Are the services of the Shared Resource Core essential to the goals of more than one Research Project?

Are the qualifications, experience, and effort commitment of the Shared Resources Core Director(s) and other key personnel adequate and appropriate for providing the proposed facilities or services?

Will the proposed Shared Resource Core provide cost effective services to the Research Center, prevent duplication, and/or increase efficiency?

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. In particular, consideration will be based on the relevance of the proposed Research Center to the scientific priorities defined in this FOA.

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 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.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. 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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR 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 following primary responsibilities:

• Determine the Research Center's directions, coordinate research approaches and procedures, and oversee the analyses and interpretation of research data;
• Oversee the timely release and sharing of specimens and data according to the approved plans;
• Participate in the development and evaluation of Pilot Projects, cross-BETRNet Projects, and cross-BETRNet activities that will cross-test novel projects;
• Participate in the annual BETRNet Steering Committee meeting, and periodic conference calls organized by the BETRNet Coordinating Center;
• Cooperate with NCI Project Scientists in the program evaluation process;
• Accept and implement all scientific and practical decisions approved by the BETRNet Steering Committee to the extent consistent with applicable grant regulations;
• Provide information to the NCI Program Directors concerning progress by submitting annual progress reports in a standard format;
• Prepare for administrative site visits by NCI staff members;
• Take advantage of collaboration with other NCI and NIH initiatives and programs, as appropriate for advancing the Center research and the BETRNet program.

The following additional responsibilities will also apply for each Research Center awardee:

• Each Research Center and the entire BETRNet program will be subject to periodic performance evaluation (coordinated by the BETRNet Steering Committee Chair) and external evaluation (coordinated by the NCI). BETRNet Awardees will be expected to participate in these evaluations;
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies;
• All institutions/organizations participating in a given Research Center will be expected to share with the BETRNet program knowledge, specimens, data, research materials, and any other resources necessary and relevant to the Research Center award.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The designated NCI Program staff members will have substantial involvement as Project Scientists in the awards under this FOA. The specific roles of the substantially involved NCI staff members include the following activities:

• Serve as the NCI lead Project Scientists and voting members of the BETRNet Steering Committee;
• Assist in avoiding unwarranted duplications of effort across the BETRNet program;
• Help coordinate collaborative research efforts that involve multiple Research Centers;
• Monitor the operations of the BETRNet Research Centers and make recommendations on overall project directions and allocations of funds;
• Review the progress of individual Research Centers and specific activities shared among the Research Centers and Coordinating Center;
• Participate in the development and evaluation of cross-BETRNet Projects;
• Co-organize and participate in the annual BETRNet Steering Committee meeting;
• Participate as Collaborators of the BETRNet investigators in some shared activities, if appropriate;
• Assist the BETRNet awardees as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures;
• Evaluate the adherence of BETRNet awardees to approved resource sharing plans.

Areas of Joint Responsibilities include:

The BETRNet Steering Committee will serve as the main governing board of the BETRNet program.

The committee will consist of the following voting members:

• The PD(s)PI(s) of each awarded Research Center who will collectively have one vote;
• The PD/PI of the Coordinating Center and a designated senior investigator who will collectively have one vote; and
• The NCI Project Scientists who will collectively have one vote for the NCI.

The BETRNet Steering Committee will meet at least one time per year in a face-to-face meeting. A chair of the BETRNet Steering Committee will be selected at the first meeting to coordinate the committee's operation. The BETRNet Steering Committee chair will meet by teleconference with NCI Project Scientists as needed to address program issues.

Additional non-voting members who can serve in an advisory capacity may be added to the BETRNet Steering Committee as needed by a decision of the existing voting committee members. These additional non-voting members may include other NCI and NIH Program Staff members and/or Program Staff members from other Federal agencies.

The BETRNet Steering Committee will have the following primary responsibilities:

• Oversee the overall BETRNet program and review its research progress;
• Review the potential of shared support infrastructure(s) at individual Research Centers to serve the needs of other Research Centers and the entire program;
• Develop procedures for soliciting and evaluating ideas for pilot projects across the BETRNet as well as criteria for their prioritization and approval;
• Ensure that the Research Centers and the Coordinating Center take advantage of existing NCI and NIH resources and programs;
• Make recommendation for termination of pilot projects that become unpromising or unproductive;
• Participate in the development of the agenda for the annual Steering Committee meeting to present scientific progress and future plans from BETRNet investigators.
• Establish advisory groups as necessary to ensure the progress of individual Research Centers as well as of the entire BETRNet program.
• Ensure that individual BETRNet members (i.e., Research Centers and Coordinating Center) accept and implement as appropriate actions (recommendations, directions, etc.) approved by the BETRNet Steering Committee.

Dispute Resolution:

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 regulation 42 CFR Part 50, Subpart D and DHHS regulation 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 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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 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)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Rihab Yassin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6230
Email: [email protected]

Ellen Richmond, MS, GNP-BC
National Cancer Institute (NCI)
Telephone: 240-276-7043
Email: [email protected]

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

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
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.