Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the NOFO) 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

.Program Objective

The objective of the Silvio O. Conte Digestive Diseases Research Core Centers (DDRCCs) is to bring together, on a cooperative basis, basic and clinical investigators to enhance the effectiveness of their research related to digestive and/or liver diseases and their complications. DDRCCs are meant to improve communication among investigators and to integrate, coordinate, and foster interdisciplinary research involving the etiology, treatment, and prevention of digestive and/or liver diseases. To accomplish this, the DDRCC supports a group of established investigators actively conducting programs of important, high-quality research that relates to a common theme in digestive diseases or liver diseases research. Thus, the purpose of a DDRCC is to provide the capability for accomplishments greater than those that would be possible by individual research project grant support alone. Applicants are encouraged to consult NIDDK staff concerning plans for the development of the DDRCC and the organization of the application.

This Notice of Funding Opportunity (NOFO) aligns with the Mission and Vision of the NIDDK Strategic Plan for Research, including the theme of empowering a multidisciplinary workforce, engaging a broad range of partners, and pursuing pathways for the health of all. Specifically, this NOFO aligns with the scientific goals 1.1, 1.3. 1.4. 2.3 and 2.5, of the Strategic Plan.

Institution and Research Base

A DDRCC must be an identifiable unit within a single university medical center or a consortium of cooperating institutions, including an affiliated university. An existing program of excellence as evidenced by productivity and peer-reviewed research funding in the area of digestive and/or liver diseases within NIDDK's mission is a prerequisite before applying. The currently funded research base provides the major support for the investigators, i.e. Center members, who would benefit from a Center's shared resources. The research base includes only currently funded, peer-reviewed research grants awarded to the applicant institution/consortium. These may be a mix of Federal and privately funded research awards or research career development awards. Moreover, there must be sufficient Federal support within the base to fulfill the requirement for a minimum of two federally funded Center members utilizing each Biomedical Research Core. Training grants, education grants, and fellowship awards are not considered part of the research base funding. Focus, relevance, interrelationships, quality, productivity, and, to some extent, quantity are all considerations in judging the adequacy of the research base. Importantly, quantity at the expense of other considerations should be avoided. A research base that has diminished focus because of inflation with the inclusion of grants with tangential relevance to digestive or liver diseases within the NIDDK's mission or the Center's theme should be avoided.

The absolute level of research base support must be sufficient to warrant the addition of a Center, typically at least $3 million per year in direct costs. At least 30 percent of the total funding contributing to the research base must be secured from the NIDDK. Since "Facilities and Administration" costs vary considerably between institutions, these should not be included in the calculation of the research base. Although collaborations are encouraged, the research base includes ONLY support for the investigators at the applicant institution/consortium.

Collaborations with investigators outside of the applicant institution/consortium or between DDRCCs are encouraged. However, they are optional. They often benefit the DDRCC's research base. Examples of benefits resulting from collaboration with an investigator outside of the applicant institution/consortium include enhanced quality/impact of the research base's scientific output, increased productivity, or peer-reviewed funding arising directly from the collaboration. Examples of benefits resulting from collaboration with one or more other DDRCCs could be more efficient use of resources by cooperating across DDRCCs, an augmented enrichment program, enhanced quality/impact of the DDRCC's scientific output, increased productivity, or peer-reviewed funding arising directly from the collaboration. Likewise, collaborations with other Core Centers supported by other NIDDK Center Programs are also encouraged and might similarly benefit the DDRCC's research base.

A DDRCC must have a central research focus or theme. The central focus must be a gastrointestinal/liver disease, group of diseases, or functional studies relating to digestive and/or liver diseases within the mission of the NIDDK. Examples of gastrointestinal disease-related central focus include, but are not limited to, inflammatory bowel disease, functional bowel disorders, pancreatitis, pediatric gastrointestinal diseases and HIV/AIDS-related gastrointestinal conditions. Examples of liver disease-related central focus include, but are not limited to, liver conditions such as viral hepatitis, nonalcoholic steatohepatitis, immune mediated liver diseases, pediatric liver diseases, and cirrhosis as well as their liver-specific complications. Examples of functional studies appropriate for a central focus include, but are not limited to, gastrointestinal physiology, gastrointestinal mucosal immunology, gastrointestinal motility, actions of gastrointestinal hormones, role of the gastrointestinal tract in obesity, gastrointestinal physiology, liver physiology, and gene therapy for digestive or liver diseases. The theme should be cohesive and well-articulated to ensure a DDRCC with components that will substantially advance a defined area of NIDDK-related science.

Existing, competing Centers are encouraged to focus their efforts. The direct cost cap for DDRCCs has not been increased in recent years and thus more focused DDRCCs might be necessary to avoid diluting the effectiveness of the limited Center support available. Therefore, it is not necessary for each competing Center to show growth in their research base when they have made the strategic decision to focus their research base (i.e. Center membership) rather than continuously expand. A flat or even slightly reduced research base in a renewal application is acceptable. When a reduction results in a more thematically focused DDRCC, with added benefit to Center members, this is appropriate and viewed as a positive development as long as the funds requested are well justified.

Overlaps in the research base among NIDDK-funded Centers should not inappropriately inflate the research base of any Center.

Non-research base investigators at the applicant institution or elsewhere may be encouraged to make use of the core facilities, collaborate with Center members, and participate in enrichment activities when space, time, and funds permit.

DDRCCs are expected to have "members", and the criteria for becoming a DDRCC member must be clearly defined and well justified. All research base investigators must be DDRCC members. Suitable criteria for membership include peer-reviewed independent funding, participation in DDRCC-related research, and need for the use of core facilities. Additional criteria for becoming a DDRCC member are also permissible, but eligibility criteria must be clearly defined and well justified. Designation of an individual without the need for use of core facilities as a Center member should be rare and must be well justified. Additional membership categories/subsets of members based on a researcher's degree of participation or other quantitative measures are acceptable, but eligibility criteria must be clearly defined and well justified.

Plan for Enhancing Diverse Perspectives (PEDP)

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

Center Structure and Activities

Biomedical Research Cores

The DDRCCs are based on the core concept. Cores are defined as shared resources that foster productivity and benefit a group of investigators working to accomplish the stated goals of the Center. Cores should provide specialized technical resources, services, and/or other expertise that enhance the efficiency and productivity of Center members. The proposed Core services should be ones that are not readily available or are not cost-effective when supplied from commercial sources, or which are technically challenging or require specialized expertise, equipment, or infrastructure. Each proposed Core must be utilized by a minimum of two federally funded investigators (with projects other than training grants, education grants, or fellowship awards) who are Center members.

When appropriate, Core staff should provide instruction for investigators, laboratory personnel, and/or fellows to learn, and then become proficient in, technologies that will become part of the repertoire of the user's laboratory. Teaching new or complex techniques and methodologies is an important function of a Core.

When proposed core services are already available through the research institution (e.g. via an institutional core), there must be compelling justification for their support through the DDRCC. Strategies for preventing duplication of services between centers at the applicant institution or for collaboration between DDRCCs to maximize use of Core resources at each DDRCC are encouraged.

In addition to providing products or services, a Core must ensure appropriate quality control and maintain a record of use. Limited developmental research is also an appropriate function of a Core facility as long as it is directly related to enhancing the function or usefulness of the Core and is not an undertaking that should more appropriately be funded through other mechanisms. Plans for responding to the changing needs of the Center members should also be a part of each Core.

Two to six biomedical research Cores are usually included in a Center. Examples of Core services/resources include, but are not limited to, imaging facilities; transgenic or gnotobiotic animal units; microbiome and metagenomics services; and membrane, cell or tissue preparation and/or storage facilities.

Centers are encouraged, but not required, to interact with the broader research community, serving as resources to support research of importance to NIDDK. Therefore, Core usage by (1) Members of other DDRCCs; (2) Members of other NIDDK-funded Centers; and (3) Non-Center members, both locally and nationally, is encouraged when Core capacity allows and institutional policies can be accommodated.

If a Human Core, Clinical Core, or Translational Core is submitted (rather than a Clinical Component or a clinical element), such Cores must be utilized by two federally funded projects.

Administrative Core

Each Center must include an Administrative Core responsible for allocation and oversight of Center resources. The Administrative Core is expected to ensure the coordination and integration of the Center's components and activities. Administrative Core personnel provide support for the required External Advisory Committee and the internal committee structure of the Center. The Administrative Core should have a process to a) assess the productivity, effectiveness, and appropriateness of Center activities; b) determine criteria and the selection process for Center membership; and c) foster collaborations and scientific opportunities among its members. In addition, all DDRCCs will be required to maintain an institutional Center website, with the Administrative Core taking primary responsibility for its curation and oversight, as well as for ensuring proper and seamless integration of the Center website with the NIDDK DDRCC program website.

Clinical Element or Clinical Component

The clinical element or Clinical Component can serve as a resource, a focal point, and a facilitator for translating work supported by the DDRCC into practical therapies for digestive and liver diseases. Investigators, therefore, need not be funded directly for clinical studies to justify the inclusion of this unit. Likewise, individual researchers do not need to be funded directly for clinical studies to use the service or expertise of the clinical element or Clinical Component. Providing the capability for translating basic research findings into a clinical setting is the goal of the clinical element or Clinical Component for those Centers wishing to build this part of their research base.

A clinical element may exist as part of a Core, usually the Administrative Core. Alternatively, a separate, full-fledged Clinical Component is also an option, if the requirements for it can be met. Besides leading to a better understanding of the etiology and natural history of disease, a clinical element or Clinical Component might provide biostatistics support; help with clinical study design; foster collaboration among researchers; aid in recruitment of subjects for clinical studies; support epidemiological studies in areas of digestive and/or liver diseases; or provide modest funding for tissue, DNA, serum storage, or other human specimen storage. In addition, a clinical element or Clinical Component may help Center members to effectively address NIH policies concerning inclusion of women, minorities, and people across the lifespan in clinical studies.

Pilot and Feasibility Program

The Pilot and Feasibility Program (P and F Program) provides modest support (typically up to $50,000 per year) for new initiatives or feasibility research studies. P and F Programs are intended to provide support for investigators to collect preliminary data sufficient to support a grant application for independent research support and/or to test a novel, even high-risk, hypothesis. P and F studies may (1) provide support for new investigators; (2) provide support for established investigators who will have no independent R01 or R01-equivalent grant support if they do not secure a substantial grant award in the near future; or (3) encourage investigators from other areas of biomedical research to apply their expertise to an area of need in digestive disease research. P and F awards may be issued to investigators with research appointments outside of the applicant institution/consortium.

P and F projects are expected to support research that primarily aligns with NIDDK's scientific mission rather than digestive or liver disease research that is better aligned with the mission of another NIH Institute of Center.

P and F support is not intended for large projects by established investigators that should be submitted as separate research grant applications, nor is it intended to provide bridging support for established investigators who are PI of one or more R01 or R01-equivalent grants that will be active for at least two years. P and F funds are also not intended to support or supplement ongoing funded research of an investigator.

Named Supported Investigator (Optional)

Each DDRCC may request salary support for a P and F Project recipient whom they designate as a Named Supported Investigator (NSI). The individual selected must be named in the application and be a junior investigator and a permanent resident or US citizen. Individuals are eligible only once for this support. Subsequent candidates for this position are nominated by the Center and reviewed by its External Advisory Committee. Appointment of the NSI is contingent upon the concurrence of the External Advisory Committee and the NIDDK DDRCC program director.

Enrichment Program

DDRCCs are expected to support enrichment activities such as visiting scientists, seminars, and research forums as well as other appropriate, innovative means to support the goals of the Center, e.g. short courses, mini-sabbaticals, joint activities with other DDRCCs, etc. Also, limited travel support may be requested to allow DDRCC investigators to present scientific findings, to learn new laboratory techniques, to develop new collaborations, or to engage in scientific exchange.

In all cases, the Enrichment Program should further the overall aims and objectives of the DDRCC as well as its Cores. Creative new programs, not precluded by NIH or NIDDK, are encouraged. While DDRCCs cannot support stipends for postdoctoral fellows, the environment fostered by the existence of the Center with its core facilities in conjunction with the Enrichment Program educational opportunities should serve to foster the careers of postdoctoral fellows and junior faculty, including K awardees.

Center Evaluation

It is anticipated that research advances, development of new research technologies/methods, and the changes in composition of the research base will require existing DDRCCs to evolve over time. DDRCCs are encouraged to develop a plan to continuously evaluate and respond to the changing needs of their research base members by adding, eliminating, or expanding Cores/core services during the course of the DDRCC.

DDRCC Directors' Meeting

Every 12-18 months, all DDRCC Directors and Center administrators are expected to attend a meeting at one of the DDRCCs to exchange information, highlight the host Center, and interact with NIDDK senior staff.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

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

Only institutions at which there is a strong ongoing base of digestive and/or liver diseases-relevant research that relates to the proposed theme of the Center are eligible. The already funded research base must have at least $3 million per year in direct costs of supported research within a proposed theme area that is of primary interest to the NIDDK. These may be a mix of Federal and privately funded research awards or research career development awards. However, at least 30 percent of the total funding contributing to the research base must be secured from the NIDDK. Moreover, enough awards within the research base must be Federal to fulfill the requirement that each Biomedical Research Core must be utilized by a minimum of two federally funded Center members. Training grants, education grants, and fellowship awards are not considered part of the research base funding. Since "Facilities and Administration" costs vary considerably between institutions, these must not be included in the calculation of the research base.

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 not 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Only one application per institution (normally identified by having a unique entity identifier (UEI) number or NIH IPF number) is allowed.

NIH will not accept duplicate or highly overlapping applications under review at the same time per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

• 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:

John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

Overall Component

When preparing the application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project Summary/Abstract: Describe the scientific theme of the DDRCC and the need for a Cores Center to support the investigators in the research base. Include the number of Center members and the overall total direct costs present in the digestive and/or liver research base. Specify the total direct costs of NIDDK awards contributing to the research base. Provide a brief overview of the research base as it relates to the theme of the Center as well as an overview of the Biomedical Research Cores, the P and F Program, the Enrichment Program, and, if requested, the Clinical Component.

Project Narrative: In 1-3 sentences describe the relevance of the research to be supported and facilitated by Center Activities (Core services, P and F program, and Enrichment Program) to public health.

Facilities and Other Resources: Describe the existing environment and facilities briefly in the context of how the Center will use or change existing access, space, and usage; include space maps as needed. Scientific personnel and institutional resources capable of supporting the research must be available.

Equipment: A general listing of major, shared pieces of equipment used by the Center members should be provided. Note: Specific research core facilities, equipment and special resources should be listed in each proposed biomedical research core component.

Other Attachments: The following "Other Attachments" must be included with the Overall Component to aid in the review of applications. The filename provided for each attachment will be the name used for the bookmark in the application image. All attachments must be in .pdf format.

Grant Support: Please title this attachment "Grant Support" and include all Federal and non-federal grant support for Center members. Complete and organize alphabetically by the last name of the Center Investigator who is listed as the Project Director/Principal Investigator (PD/PI) on the grant. Include Supporting Organization/Grant Numbers, Complete Grant Title, Project Period, Annual Direct Costs, and identify any other NIDDK Centers if the grant is included as part of its research base as well. The attachment should include the following three tables, in order.

• Table A.1, "Current Digestive Diseases Grant Support" (This is the support contributing to the Research Base): Include R-series, individual K-series, U01s, DP-series, P01s, and other similarly peer-reviewed grants funded through other Federal Agencies or non-federal groups. These awards should be potential or likely users of Center services.
• Table A.2, "Other Digestive Diseases Grant Support": Include individual fellowships, institutional training and clinical career development awards, and center grants. Include grants with both federal and nonfederal support.
• Table A.3, "Pending Digestive Diseases Grant Support": Applications to be included are R-series, individual K-series, U01s, DP-series, P01s, and other similarly peer-reviewed applications for funding through other Federal Agencies or non-federal groups. These awards should be potential or likely users of Center services.

Examples of how Tables A.1, A.2 and A.3 might be formatted are provided for applicant assistance with this requirement (see: DDRCC Resource page).

Biographical Sketches of Center Research Base Investigators: Please title this attachment "Center Member Biographical Sketches". Provide biographical sketches for all Center members, as defined by the Center within the application. List each membership category separately if more than one category of Membership is designated by the Center and organize each list alphabetically by the last name of the Research Base Investigator. Biographical sketches should follow the NIH Biosketch format. Do not include biographical sketches for Senior/Key Personnel since those are included with the appropriate component of the application and should not be duplicated here.

Description of Center Research Base Investigators: Please title this attachment Description of Center Research Base Investigators . List each membership category separately if more than one category of Membership is designated by the Center and organize each list alphabetically by Center Member (last name). Provide a narrative description of no more than one page per research base investigator. These narratives should include: the active grant number(s), title(s), and a few descriptive sentences of the investigator’s research projects, as well as a brief description regarding what aspect of the investigator’s research justifies the use of Center core facilities. Include ONLY those grants awarded, or subcontracted, to investigators at the applicant institution or consortium, not to investigators at other locations. It is particularly important to provide a few sentences indicating the relatedness of a cited grant to digestive disease/liver research and to the theme of the DDRCC when this is not readily apparent from the project title of the grant.

Core Use by Center Members: Please title this attachment "Core Use by Center Members" and organize alphabetically by Center Member (last name, first name). List all DDRCC Members including Membership Category (only if more than one category of Membership is designated by the Center), and for each Center Member indicate those Center Core Facilities that will be used. Table B is provided for applicant assistance with this requirement (see: DDRCC Resource page)

For renewal applications only: Provide an additional Table with the same information for the "Actual Core Use by Center Members".

Center Collaborations: Please title this attachment Center Collaborations and organize alphabetically by Center Member (last name, first name). List all Center Members. Provide primary Department Affiliation, key words for research interests, names of other Center members who are collaborators (through publications, grants or research projects), and the number of collaborative publications. Table C is provided for applicant assistance with this requirement (see: DDRCC Resource page.)

Plan for Enhancing Diverse Perspectives:

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity
• The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate.
• Where possible, applicant(s) should align their description with these required elements within the research strategy sections
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured
• The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp

The following "Other Attachment" is optional for the Overall Component. The filename provided for the attachment will be the name used for the bookmark in the application image. The attachment must be in .pdf format.

Optional: Provide Charts and Tables to illustrate the structure, interactions, and leaders of the institution and the DDRCC. If included, title this attachment "Relation to Overall Center".

Project/Performance Site Locations (Overall)

Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

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

Budget (Overall)

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

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

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the broad long-term objectives of the proposed DDRCC. Provide the central theme(s) of the DDRCC. The theme may be broad or focused, depending upon the goals of the Center. However, it should also be cohesive and well-articulated in order to ensure a DDRCC with components that will substantially advance a defined area of NIDDK-related science. Outline the existing skills and technologies available in the research base as well as other resources at the institution(s) and summarize how the Center will enhance ongoing projects, assist in the development of new projects, promote diverse perspectives, respond to future opportunities, and promote collaborations leading to advances in digestive and/or liver diseases research.

Research Strategy: The Research Strategy should include the following sections.

Research Base: The DDRCC grant provides a mechanism for fostering interdisciplinary cooperation within a group of established investigators conducting high quality research on digestive and/or liver diseases. Therefore, existence of a strong, substantial research base in the thematic focus areas(s) of the DDRCC is a fundamental requirement for the establishment of a Center.

Applicants should include an overview of current research in digestive and/or liver diseases related areas being conducted at their institution in sufficient detail to allow reviewers to judge the extent and the interrelationship of ongoing research. It is recommended that the DDRCC research base be sub-divided into areas of research emphasis or research themes that link Center members and their research programs. Applicants should indicate how the establishment of a Center will provide added dimensions, such as greater focus and increased cooperation, communication and collaboration that would not likely occur without Center resources.

Presentation of the research base in the application should be done in two ways: (1) by completing a Table itemizing grant funding as described in Other Attachments; and (2) by a full narrative description of the digestive diseases research activities at the applicant institution/consortium and any collaborating institutions in the context of the theme(s) of the Center. The research of each DDRCC member should be discussed and interrelationships of research being conducted by the members should be highlighted. Since most, if not all, of the research base will have undergone separate peer review, the quality of the individual funded projects is already established. The more important aspects are: (a) interactions and interrelationships of the research efforts as well as relevance to the theme of the DDRCC; (b) uses and benefits of core services; (c) plans to develop productive collaborations among Center investigators; and (d) willingness of Center investigators to contribute to the overall objectives of the DDRCC.

Collaborative activities with individuals outside of the applicant institution/consortium or between DDRCCs is encouraged but optional. How any such collaboration benefits the research base can be described. Examples of benefits include more efficient use of resources by cooperating across DDRCCs, an augmented enrichment program, enhanced quality/impact of the DDRCC's scientific output, incorporation of additional perspectives, increased productivity, or peer-reviewed funding arising directly from the collaboration.

Membership: A high level of integration and close collaboration among DDRCC members with diverse perspectives and from different scientific disciplines is an important feature of a successful Center. Accordingly, the applicant should state considerations for DDRCC membership with specific reference to the potential of members to form interactive, collaborative, and synergistic relationships. Specific DDRCC criteria and any affiliation categories (if applicable) should be clearly defined by the applicant in order to organize and facilitate the focus of the Center's mission. Subsets of members based on their degree of participation or other quantitative measures are acceptable. Applicants should provide clear guidelines for how Center membership is defined (including, if applicable, how subsets of membership are defined), the application and selection processes for Center membership, the obligations of Center membership, and the criteria for termination of membership. Suitable criteria for membership include, but are not limited to, peer-reviewed independent funding, participation in DD research, and the need for the use of core facilities. All research base investigators must be Center members. Designation as a Center member without the need for the use of core facilities must be well justified.

Center Organization: Summarize the services, resources, and expertise provided by the proposed Biomedical Research Cores, emphasizing the support they will provide for the thematic areas of the research base. Point out novel services and resources available in the cores and describe the potential for interdisciplinary collaborations among Center Investigators.

Indicate if any of the proposed Cores will utilize or expand Cores already existing at the institution. Describe how the proposed Center will leverage existing resources and fill gaps in the services available. Leveraging existing resources is encouraged, particularly when this provides a range of services or efficiency that would not otherwise be available.

Provide a plan to determine the need for new services or instrumentation of the DDRCC members. Discuss how the Center will ensure that Center members are able to take advantage of cutting-edge technology and how services no longer required, or no longer cost-effective, will be phased out. Include information on the process of re-evaluating the needs of Center members and how evolving needs will be met.

Also describe how the Center will enhance the research base and foster the careers of its junior investigators through enrichment activities and the use of Core services/expertise.

Institutional commitment: Applicant institutions/consortia are expected to have demonstrable commitment to the Center's success. Examples of ways institutional commitment might be evidenced include, but are not limited to, financial support for Cores or other Center functions, salary support for Center staff, dedicated space, or availability of equipment. New applications should briefly describe plans for institutional commitment should the Center receive NIDDK support. Renewal applications should briefly describe both previous and ongoing instances of institutional commitment. These should be accompanied by letters of support from institutional officials verifying the commitment with specific details.

For new applications: Emphasize the anticipated impact of the establishment of a DDRCC on the research base. Include an indication of how the establishment of the Center will provide added dimensions and new opportunities for DD and related research, along with increased cooperation, communication, and collaboration among investigators.

For renewal applications: Briefly discuss the progress and accomplishments of the research base as influenced by the DDRCC; the development of multidisciplinary, collaborative, and cooperative interrelationships among Center members; and indicate any alteration in the original Center design that was instigated to meet the evolving needs of the research base. Discuss changes to the research base over the past five years to either facilitate growth or to enhance its focus instead of emphasizing growth. This should be described in a narrative fashion.

Progress Report Publications List (renewal applications only): List publications related to or derived from DDRCC support or assistance. Include PMCIDs. Table F (DDRCC Resource page) is provided for assistance with this list. The Core most significantly contributing to the work should be assigned 'primary' (P) status. All other contributing Cores are designated 'secondary' (S). Group publications by Core used, so that the number of publications (not the list of publications) that resulted from the use of each Core can be cited in each Core narrative write-up. The DDRCC should have been credited as a resource in all publications. Portions of this table should NOT be duplicated in each Core, but the absolute number of publications from this main list should be cited.

Letters of Support: Include any letters of support for the proposed DDRCC from appropriate institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the DDRCC and its goals. The parent institution is expected to recognize the Center as a formal organizational component and provide documented evidence of space dedicated to the needs of the Center, staff recruitment, salary support for investigators or technical personnel, dedicated or shared equipment, or other financial support for the proposed Center. The parent institution should provide assurance of its commitment to continuing support of the DDRCC in the event of a change in directorship. A well-defined plan for this eventuality should be in place.

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.

The following modifications also apply:

Generally, Resource Sharing Plans are expected, but they are not applicable for this component.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type Admin Core .

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

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

Project/Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Center Director 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.
• In this component, also provide biographical sketches for any consultants. For renewal applications only, provide biographical sketches for the members of the External Advisory Committee. In the additional Senior/Key Profiles section, list those Senior/Key persons in the Project Role of "Other" with Category of "Consultant" or "Advisory Committee." New applications should NOT contact potential External Advisory Committee members or provide names or biosketches for External Advisory Committee members. New applications may include the expertise or experience needed and the process by which members of an External Advisory Committee by which they will be selected in the Research Strategy.

Budget (Administrative Core)

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

Personnel: The Center Director must devote a minimum of 2.4 person months to the Center and at least 1.2 of the person months must be within the Administrative Core to ensure adequate oversight of the Center. If a multiple PD/PI application, the combined effort of the PD(s)/PI(s) must be 2.4 person months. Most Centers find that the size and complexity of a DDRCC warrant inclusion of a full-time program administrator, so salary support for this individual should be included in the Administrative Core.

Equipment: If pieces of specialized equipment, or computers, costing more than $5000 are requested, the application must identify similar equipment already available within the institution and provide a clear justification for purchase based on core service provided to DDRCC investigators. Requests for general-purpose equipment should be included only after ascertaining the availability of such items within the institution. Justify the request based on this availability. This includes all equipment in future budget years as well as the initial budget period.

Supplies: Consumable supplies directly related to the operational aspects of the Administrative Core facilities are an allowable expense.

Alterations and Renovations: Funds for the alteration and renovation of an existing structure to provide suitable space for core facilities may be requested. "Cosmetic" renovations are not appropriate.

Consultants: Include costs associated with consultants (consultant fees, per diem, and travel) when their services are required by the DDRCC, such as the members of the External Advisory Committee.

Travel: Include the costs of domestic and foreign travel only if the travel is directly related to the activities of the DDRCC. Include travel costs for the DDRCC Director, Center administrator, and others as appropriate (i.e. co-Director, core Directors) to attend the DDRCC Directors' meeting.

PEDP Implementation Costs: Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

Other Expenses: Support for development/maintenance of the Center's website may be requested as well as funds for supporting regional Center meetings, if appropriate.

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

PHS 398 Research Plan (Administrative Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the Administrative Core will contribute to the goals of the DDRCC and outline interactions of the Administrative Core with each of the other Cores, Clinical Component (if proposed) and Programs (P and F and Enrichment). Provide an overview of how the Administrative Cores will set the overall direction of the Center and ensure optimal utilization of the Center resources.

Research Strategy: The Administrative Core is key to the coordination and functioning of the Center. Therefore, describe the administrative structure of the DDRCC, including chain-of-command; committee structures (e.g. Internal Advisory Committee, P and F review committee, other oversight or management committees, and the required External Advisory Committee); and Core, Enrichment Program, and clinical element (if included) management.

The Director, who is the PD(s)/PI(s) of the application, should be assisted by one or more Associate Directors who will be involved in the administrative, scientific, or enrichment efforts of the Center and who will serve as Acting Center Director in the absence of the Director. Include a brief narrative describing the qualifications of the Director and Associate Director(s). A process must be in place to recommend a successor to the Director, if a successor becomes necessary.

The relationship of the DDRCC to the institution and the reporting lines of the DDRCC Director to appropriate institutional officials may be presented in diagrammatic form, but also provide a brief explanation in narrative form.

Include a description of the mechanism for monitoring budgetary overlap between the research projects included in the research base and the funds for the core facilities of the DDRCC, describing a mechanism to monitor the budgetary adjustments made necessary by the use of Core services. This will ensure that DDRCC investigators using Cores are able to provide a satisfactory explanation of their relationship to the DDRCC and their inclusion of charge-back fees for Core use in their individual grant budgets.

It is expected that the organization of the Administrative Core will provide a supportive structure sufficient to ensure the accomplishment of the following:

• Coordination and integration of DDRCC components and activities.
• Assessment of productivity, effectiveness, and appropriateness of Center activities and determination of Center membership, assessment of scientific opportunities, and areas for collaboration among DDRCC members.
• Organization of Center activities, such as retreats, symposia, invitation of consultants, meetings, and focus groups.
• Organization of the Internal and External Advisory Committees.
• Participation of community partners through either a Community Advisory Board or membership on the Internal Advisory Committee.
• Recordkeeping of meeting minutes and measures of success including: use of Core facilities, publications, P and F awards, and new grant applications resulting from preliminary data enabled by the DDRCC.
• Interactions with other DDRCCs, the NIDDK, and other appropriate individuals, groups, or organizations.
• Maintenance of a Center website with the Administrative Core taking primary responsibility for its curation and oversight and for ensuring proper and seamless integration of the Center website with the NIDDK DDRCC program website.

Center Evolution: Applicants must document policies and procedures for ensuring continuing evolution of Center activities, such as core services, in response to changing needs of the research base. New technologies or services might appear that should be supported, existing technologies might become less important, or economic changes might obviate the need for core services, such as the availability of cost-effective commercial services or core services provided by the research institution. Centers should address the issue of allocation of resources toward development of new technologies versus provision of services with existing technologies.

The administrative structure must include an Internal Advisory Committee (IAC) and an External Advisory Committee (EAC). New applications should neither contact potential EAC members nor list members of the EAC, but they should describe what expertise is needed and the process by which they will be selected. Renewal applications should list the current EAC members (and include their biosketches on the Senior/Key Person form) in addition to documenting the functions and effectiveness of the External and Internal Advisory Committees. The structure must also include community partners who will provide perspectives on living with digestive and liver diseases and input to the Center. This can be achieved through either participation on the IAC or establishment of a community advisory board (CAB). Additional complementary strategies for community engagement may also be included.

The final administrative structure of the Center will be left largely to the discretion of the applicant institution. However, past experience has demonstrated that the effective development of the Center programs requires close interaction between the Center director, Core/Program Leaders, appropriate institutional administrative personnel, and the members of the community in which the Center is located. Therefore, each Center applicant should establish an administrative structure that will permit the development of such interactions. Within this structure, each applicant institution must also establish a mechanism to oversee the use of funds for the proposed pilot and feasibility program. This mechanism must include the use of appropriate consultants for review from the scientific community outside the Center institution. These same consultants may be utilized, if desired, for review of other activities of the Center.

Letters of Support: Include any letters of support for the proposed Administrative Core, as appropriate. Include any letters of support from community members who serve on the IAC or CAB. Letters from members of CABs dedicated to specific Cores (e.g., a CAB associated with a biorepository) should be included in that Core's Letters of Support.

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:

Generally, Resource Sharing Plans are expected, but they are not applicable for this component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

Biomedical Research Core

When preparing your application, 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 (Biomedical Research Core)

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

PHS 398 Cover Page Supplement (Biomedical Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Biomedical Research 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.

Facilities and Other Resources: The description of the physical arrangements and instrumentation for the cores should be given special attention. Arrangements for sufficient space for core activities or for access to appropriate established facilities must be made. Centers are strongly encouraged to enter into cooperative arrangements with cores already established within their institution, or with other Centers in close proximity, when the existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. When proposing the use of a shared facility, details about access, fee-schedules, and prioritization of Center members' use of the shared facility must be described. It may be advantageous for a DDRCC to provide support for appropriate personnel to work specifically for Center members in an existing facility/core (e.g., transgenic animal core) at the institution. In that case, the designated DDRCC Core Director must work closely with the parent facility Core Director to coordinate services, unless the same individual assumes both roles.

Other Attachments: The following attachment must be included in .pdf format. The filename provided will be the bookmark in the application image.

Core Facility Use: For all applications, please title this attachment "Core Facility Use" and indicate the Core User, Funded Project that supports the Core use, Period of Core Use, Services to be used, and Estimated Use and comments. Table D is provided for applicant assistance with this requirement: (DDRCC Resource page)

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of "Core Director" 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 (Biomedical Research Core)

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

Personnel: This category should include salary support for key personnel, including the Core Director, co-Director, and other professional and technical personnel. The Core Director must devote a minimum of 0.6 person months to the Core to ensure adequate oversight. The salary amount charged to the DDRCC grant must be commensurate with the time spent on Core activities and is subject to institutional and NIH salary policies. A Core Director with the requisite expertise may devote a greater effort to the core, and with exceptionally strong justification could devote up to 12 person months. In instances where a junior scientist (who may or may not be a part of the research base) with appropriate expertise will devote a significant effort to the Core and a more senior, established expert assumes the role of Core Director, a title of core manager or core technical director might be appropriate for the junior scientist. While it is expected that all Core Directors and co-Directors will be Center members, occasionally experts in the specialty area required by the Core who are not part of the research base may be appropriate. Sufficient and compelling reasons must be given for appointing any Core Director/co-Director who is not a Center member. Salary support for technicians and other core personnel allowable in accordance with the volume and type of work in the core. Stipends for research trainees are not available through the Center. Such funding must be sought through other grant mechanisms.

Equipment: If pieces of specialized equipment costing more than $5,000 are requested, the application must identify similar equipment already available within the institution and provide a clear justification for purchase based on core services provided to DDRCC investigators.

Requests for general-purpose equipment should be included only after ascertaining the availability of such items within the institution. Justify the request based on this availability. This includes, when possible, all equipment in future budget years, in addition to the initial budget period.

Supplies: Consumable supplies directly related to the operational aspects of the core facilities are an allowable expense. This includes office materials as well as laboratory supplies. The supply budgets of separately funded individual research projects must be appropriately reduced to reflect such support, thus eliminating duplication.

Research Patient Care Costs: Research patient care costs (both in-patient and out-patient) are an allowable expense. Attempts should be made to utilize existing clinical facilities, such as those supported by Clinical and Translational Science Awards (CTSAs) and individually supported beds.

Request costs relating to the clinical research efforts of DDRCC investigators ONLY if there is no overlap with other funding. Costs already budgeted in individual projects should be appropriately reduced if such costs are to be transferred to the Center. The DDRCC is not intended to be a facility for health care delivery. Thus, only those patient costs directly related to research activities may be charged to the Center.

Alterations and Renovations: Funds for the alteration and renovation of an existing structure to provide suitable space for core facilities may be requested. Cosmetic renovations are not appropriate.

Consultants: Include costs associated with consultants (e.g. consultant fees, per diem, teleconferences, and travel) when their services are required by the Core.

Travel: Include the costs of domestic and foreign travel for core personnel only if the travel is directly related to the activities of the DDRCC.

Other Expenses: Funds for equipment maintenance/service contracts may be requested, but should reflect only an equivalent percentage of the service contract based on the overall use of the specified equipment by Center investigators versus other users. The budget justification for any maintenance/service contracts should document use of the equipment by Center members. Only in very rare cases should full support for a maintenance/service contract be requested, and strong justification must be provided in such cases.

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 (Biomedical Research Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state the aims of the Biomedical Research Core.

Research Strategy: Provide the rationale for establishing or continuing the Core and the activities of the Core. Cores may be proposed to support any research activity of the Center. The description of each Core should indicate how it will support the Center’s research base in a cost-effective manner.

Include a definition of qualified users and provide a list of research base investigators who will use the core, including the expected extent of their proposed use. Each proposed Core must be utilized by a minimum of two federally funded investigators who are Center members. Emphasize the anticipated benefits that investigators will derive from using core facilities. Criteria for use and for prioritization must be included in the application.

Present the organization and proposed mode of operation of each core. As appropriate to the core, a charge-back system may be developed to allow investigators to utilize its services. Financial justification such as comparative costs of other sources of proposed core services as well as plans for cost recovery, i.e. charge-back fees, from users should be detailed.

Charge-back fees are allowable budgetary items in the investigators' individual research project grants. A system of payment management/accounting must be established such that it is clear to the individual users, the institutional business office, and the NIDDK what the charge-back system covers and how funds recovered are being used. This will enable Center investigators to appropriately adjust the budgets on their own grants and ensure accountability.

Each Core must have an operational plan which must include methods to:

• Assure quality control
• Prioritize investigator use
• Monitor core use
• Adapt to new technology and to the needs of the DDRCC members.

Limited use of cores by investigators in other fields who are not Center members is encouraged, as is use by trainees, students, and junior faculty, but rules to regulate this use should be defined. If the core is used for training, the approach to and extent of training being performed in the Core should be detailed. Training is an appropriate and worthwhile activity of a Core and is encouraged.

Any Core with a minimum number of users must develop plans to broaden the number of Core users. Such plans are particularly important for any Core that, while not extensively used, is considered essential by the DDRCC administration.

Describe any plans to use the Core for limited developmental research, including the relevance of this research to Core services, effectiveness, and adaptability.

Since DDRCCs are strongly encouraged to enter into cooperative arrangements with established cores at the applicant institution or at other DDRCCs offering a similar type of service, describe the nature of any cooperative arrangements, access, fee-schedules, the prioritization plan, and the methods to monitor use under these circumstances. It may be advantageous for a DDRCC to provide support for appropriate personnel to work specifically for DDRCC members in an existing facility/core (e.g. transgenic animal core) at the institution. In this case, the designated DDRCC core Director must work closely with the parent facility core Director to coordinate services, unless the same individual assumes both roles. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. Therefore, financial justification such as comparative costs of other sources of proposed core services as well as plans for cost recovery from users should be detailed.

Because cooperation between DDRCCs is also encouraged, but not required, any plans to work with one or more other established DDRCCs may be provided and documented along with a description of the benefit(s) to the Center being proposed. Benefits might include, but are not limited to, cost savings, ability to provide additional or improved services, or enhanced productivity by Center members. Likewise, collaborations with other Core Centers supported by other NIDDK Center Programs are also encouraged and may also be documented and described.

Proposed DDRCC cores may be an institutional shared research core. In those cases, applicants must provide a rationale for using institutional cores, such as:

• Support for the existing resource through the DDRCC will provide added value and access to the resource beyond that which would be provided by paying for the use of the resource through a fee-for-service process;
• The institutional/departmental core represents a unique resource which would not otherwise be available (e.g., is too costly, too labor intensive, or too specialized to be available to individuals;
• The institutional/departmental core provides a service done more effectively (i.e., more inexpensively or by specially trained personnel or requiring specialized facilities) than would be feasible in individual cores (e.g. histology, animal models), and thus using the institutional/shared core avoids duplication and lowers costs for DDRCC members; and/or
• The service/instrumentation/expertise in the centralized core can only exist with the participation of multiple centers and their user fees, and DDRCC members need the service/instrumentation/expertise in proportion to the buy-in from the DDRCC.

Program Income: Centers may, where appropriate, develop a program income (re-charge/fee-for-service) system for use of Core services. Such a program income system would constitute a method of charging Core users for their usage of expertise and research resources. Program income must be re-invested into direct support of Center-related activities and/or expenses and may not generate a profit for the Center.

For renewal applications: Information relative to cores in renewal applications should generally cover all of the same points as initial applications. In addition, past performance and accomplishments should be described and highlighted. The effect of the service provided by a core on investigator productivity and cost-effectiveness should also be addressed. Any changes in services provided should be documented. Any Core usage by (1) Members of other DDRCCs; (2) Members of other NIDDK-funded Centers; and (3) Non-Center members, both locally and nationally, should be documented.

Also, for renewal applications, include information on past use of the core services for which further funding is not being requested, as well as a brief explanation of the reasons for deleting the services, combining facilities, or creating new Cores.

Progress Report Publications List (renewal applications only): Core productivity and accomplishments as demonstrated by peer-reviewed research publications supported by the core should be documented by listing the numbers of the relevant publications from Table F (DDRCC Resource page), which was attached in the "Overall' component. The DDRCC should have been credited as a resource in all publications. This acknowledgement provides evidence of Core use. Do not duplicate Table F in each Core.

Letters of Support: For any collaborative links between the CTSA and a specific Biomedical Research Core, a letter of support should be included within the relevant Core. Also, provide letters to address the career potential of, and institutional commitment to, junior scientists who serve as core managers/technical directors. Letters of support from members of CABs that are specifically focused on a particular Core should be included within the relevant Core. In addition, other letters of support for the proposed Core may be included, as appropriate.

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.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Biomedical Research Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

Clinical Component

When preparing your application, use Component Type Clinical

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

SF424 (R&R) Cover (Clinical Component)

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 (Clinical Component)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical 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.

Project /Performance Site Location(s) (Clinical Component)

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 (Clinical Component)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Clinical Component Director 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 (Clinical Component)

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

Personnel: This category should include salary support for key personnel, including statistical support, patient coordinators, database managers, and other staff necessary for the functioning of the Clinical Component.

Equipment: If pieces of specialized equipment costing more than $5,000 are requested, the application must identify similar equipment already available within the institution and provide a clear justification for purchase based on the service provided to DDRCC investigators. Requests for general-purpose equipment should be included only after ascertaining the availability of such items within the institution. Justify the request based on this availability. This includes all equipment in future budget years as well as the initial budget period.

Supplies: Consumable supplies directly related to the operational aspects of the clinical Component are an allowable expense. This includes office materials as well as laboratory supplies. The supply budgets of separately funded individual research projects must be appropriately reduced to reflect such support, thus eliminating duplication.

Research Patient Care Costs: Research patient care costs (both in-patient and out-patient) are an allowable expense. Attempts should be made to utilize existing clinical facilities, such as those supported by Clinical and Translational Science Awards (CTSAs) and individually supported beds.

Request costs relating to the clinical research efforts of DDRCC investigators ONLY if there is no overlap with other funding. Costs already budgeted in individual projects should be appropriately reduced if such costs are to be transferred to the DDRCC Clinical Component. The DDRCC is not intended to be a facility for health care delivery. Thus, only those patient costs directly related to research activities may be charged to the Center.

Alterations and Renovations: Funds for the alteration and renovation of an existing structure to provide suitable space may be requested. Cosmetic renovations are not appropriate.

Consultants: Include costs associated with consultants (consultant fees, per diem, and travel) when their services are required by the clinical component.

Travel: Include the costs of domestic and foreign travel for clinical component personnel only if the travel is directly related to the activities of the DDRCC.?

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 (Clinical Component)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state the aims of the Clinical Component.

Research Strategy: Describe the services to be provided by the Clinical Component as well as the potential number of users, including the rationale for establishing this Component and how it will be used to translate the work of the DDRCC research base investigators into practical therapies for digestive and/or liver diseases. Center members need not already be funded for translational work to take advantage of the services of the Clinical Component.

Charge-back fees for the Clinical Component are allowable budgetary items in the investigators' individual research project grants. A system of payment management/accounting must be established such that it is clear to the individual users, the institutional business office, and the NIDDK what the charge-back system covers and how funds recovered are being used. This will enable Center investigators to appropriately adjust the budgets on their own grants and ensure accountability.

Program Income: Centers may, where appropriate, develop a program income (re-charge/fee-for-service) system for use of Clinical Component services. Such a program income system would constitute a method of charging Clinical Component users for their usage of expertise and research resources. Program income must be re-invested into direct support of Center-related activities and/or expenses and may not generate a profit for the Center.

For renewal applications: Include a description of past use of the Clinical Component, highlighting benefits to the Center members as well as any changes to the services provided.

Letters of Support: If a CTSA will be involved in the Clinical Component, include letters from the CTSA Director and relevant staff. In addition, other letters of support for the proposed Core may be included, as appropriate.

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.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Clinical Component)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Pilot and Feasibility Program

When preparing your application, use Component Type P and F Program

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

SF424 (R&R) Cover (Pilot and Feasibility Program)

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 and Feasibility Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Pilot and Feasibility Program)

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.

Other Attachments: The following attachments must be included in .pdf format.

Pilot Project Outcomes (for renewal applications only): Please title this attachment "Pilot Project Outcomes" and list all P and F Projects supported in the most recent 5 or, if applicable, 10-year period. Include the dates and amount of the award, the title of the project, category of P and F recipient, subsequent funding, and whether the recipient is still involved in GI and/or liver research. Table E is provided for applicant assistance with this requirement (see: DDRCC Resource page).

Pilot Summary /Abstract (for all applications): Please title this attachment "Pilot Project Information" and provide a Project Summary/Abstract for each proposed pilot project (including any proposed Core use), as well as the biographical sketch of the investigator for each of the proposed pilot and feasibility projects. For renewal applications, this information should be from the most recently funded group of pilot and feasibility applications. New applications that have made awards through a P and F program that was set up to demonstrate feasibility and/or that is intended to be the basis for a P30 program, may provide information about awards made under those P and F programs.

Project /Performance Site Location(s) (Pilot and Feasibility Program)

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 and Feasibility Program)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of P and F Program Director 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 and Feasibility Program)

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

Personnel: Include salary support for the P and F Program director, who must devote sufficient effort to manage and provide oversight, typically 0.6 to 1 person month. If requested, include the salary for the Named Supported Investigator. Support for this individual is limited to 3 years and cannot exceed $90,000 per year, additional appropriate fringe benefits, and 9.6 person months effort.

Other Expenses: Include funds to support the number of P and F projects requested. These funds are capped at $150,000 direct costs per year for the program.

Consultants: Include costs associated with consultants (e.g. consultant fees/honoraria, per diem, and teleconferences) when their services are required by the Pilot and Feasibility Program, such as any external reviewers for P and F applications.

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 and Feasibility Program)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state the goals of the Pilot and Feasibility Program.

Research Strategy: Describe the overall goals and structure of the Pilot and Feasibility Program. Describe its management plans, including both internal and external review mechanisms along with an outline of the plans for future years of the P and F Program. While the management of the P and F Program is left to the discretion of the DDRCC, the following must be described in the application:

• A vision or mission statement for the P and F program must be elucidated. This statement should describe how the P and F program will support impactful digestive and liver disease research primarily within the mission of NIDDK as well as facilitate a thriving research community.
• A plan for including the Community Advisory Board or community members/patient advocates serving on the IAC in the P and F program's structure.
• A process to solicit applications for P and F program funding must be established and explained. This should include a description of how the process will attract applications that are aligned with the P and F program's vision or mission statement.
• A process for the scientific merit review of P and F projects must be established and explained. At least one reviewer from outside the DDRCC must be used to evaluate each application. Details of handling the review will be left to the DDRCC, although all reviewers should assign impact scores in accordance with the NIH system. Copies of all of the projects with written documentation of the reviews, impact scores, and final action should be retained by the DDRCC. These records should be available to NIH staff, if requested. The application should explain how the process will be free of bias and aligned with the P and F program's vision or mission statement.
• A process for selecting P and F projects for funding through the P and F program following scientific merit review should be outlined and explained. This should include a description of how the selection process is informed by the vision or mission statement.
• A mechanism for the oversight and review of ongoing P and F projects should be developed as a requirement for a second or third year of funding.
• A mechanism to terminate P and F projects must be established. Studies may be terminated by the DDRCC administration before their approved time limit for various reasons such as (1) the investigator receives outside funding for the project; (2) the project was found not to be feasible; or (3) the investigator left the DDRCC institution. When a project is terminated, the DDRCC may use the unspent funds to either make new awards for P and F projects or to supplement ongoing P and F projects.
• A plan for tracking the success of the P and F Program should be established. A record of scientific publications, abstracts, and grant applications submitted/funded, as well as information on whether the investigator remains in DD-related research is important. Staff of the NIDDK uses this record to determine whether the P and F Program is a useful component of the Center which serves to encourage investigators to remain in DD-related research.
• For applications proposing P and F Programs that will accept projects that include Delayed Onset Human Subjects Research or Delayed Onset Clinical Trials, a plan to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects.

Each DDRCC is strongly encouraged to involve the External Advisory Committee in the management of the P and F Program. P and F grant recipients are encouraged to collaborate or consult with any biostatistics component supported by the DDRCC or otherwise available at the applicant institution and to utilize the Biomedical Research Core facilities or the Clinical Component of the DDRCC.

Clearly indicate the Named Supported Investigator, if such a position is being requested, and how and why he/she was selected. Each DDRCC may request salary support for a P and F project recipient whom they designate a Named Supported Investigator (NSI).

All applicants should provide an assessment of the relevance of proposed P and F projects to the specific goals of the DDRCC as well as the P and F program's ability to encourage innovative research. Moreover, the P and F program is intended to primarily support digestive and liver research aligned with NIDDK's mission as opposed to digestive and liver disease research that is primarily aligned with another NIH Institute or Center. In this context, the research strategy should also include a brief, no more than one page synopsis for 4 representative P and F project applications that have been vetted by the Center.

Each synopsis should include:

• Budget and number of years associated with the pilot project
• Alignment of the P and F project with the P and F program's vision/mission
• Relevance of the P and F project to NIDDK's scientific mission
• Name, department affiliation, and eligibility category of the P and F investigator
• Proposed Core use
• Brief description of the project; including hypothesis, one sentence description of each Aim, one to three sentences identifying the conceptual and/or technical innovation, relationship to the Center's theme and goals; how the project will benefit from specific collaborations with Center members if applicable, and plans for follow-up upon the successful completion of the project.

For new applications: These should be the best applications received by the DDRCC and reviewed in the manner proposed for all future P and F applications. If the P and F awards have been made through this process, that information may be provided.

For renewal applications: These should be from the most recent group of funded P and F projects.

Renewal applications should describe the success of their ongoing program. Indicators of a successful program include the number of P and F projects leading to successful career development awards, research project grants, or equivalent foundation grants and how they have benefited the recipients' career trajectories and the Center's scientific environment. The direct costs awarded to these grants is less important, because it conveys the budget required to accomplish the Aims and not the project's scientific merit. Other important outcomes associated with a successful program include publications, professional opportunities, and the development of new technologies or resources. New applications that have had demonstration P and F Programs may also describe their success.

Requirements: Each Center must propose to support a minimum of 2 pilot and feasibility studies from DDRCC funds each year.

Progress Report Publications List: Productivity and accomplishments of the P and F Program as demonstrated by peer-reviewed research publications supported by the Center should be documented by listing the number(s) of the relevant publication(s) from Table F, which was attached in the Overall component. Do not replicate publication lists in the Pilot and Feasibility Program section.

Letters of Support: Include any letters of support for the Pilot & Feasibility Program by appropriate institutional officials at partnering organizations (other than the parent institution), if applicable.

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.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Pilot and Feasibility Program)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

Enrichment Program

When preparing your application, use Component Type Insert Name.

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

SF424 (R&R) Cover (Enrichment Program)

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 (Enrichment Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Enrichment Program)

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.

Other Attachments: Competing Centers may include information related to the Center-supported Enrichment Program activities (such as Center retreats, symposia, workshops, meetings, specialized courses, seminar series, etc., illustrating the interactions among Center members and other investigators, as well as other training and educational opportunities) in the application. New Applications that have Enrichment Program activities that are intended to continue as part of their DDRCC Enrichment Programs, may provide this information for those activities. This attachment is optional. This should be loaded as a single, combined file in PDF format titled "Enrichment Program".

Project /Performance Site Location(s) (Enrichment Program)

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 (Enrichment Program)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Enrichment Program Director 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 (Enrichment Program)

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

Personnel: This category should include salary support for key personnel, including the Enrichment Program Director and any other professional and administrative personnel. The Enrichment Program Director must devote a minimum of 0.6 person months to ensure adequate oversight of the Program. The salary amount charged to the DDRCC grant must be commensurate with the time spent on Program activities and is subject to institutional and NIH salary policies.

Other Expenses: Include funds to support Enrichment Program activities such as workshops, research forums, symposia, Center retreats and seminar series. Funds for Enrichment Program- associated activities such as the printing and distribution/mailing of brochures, programs, and meeting materials, as well as posters and other advertisement materials, may be requested.

Consultants: Include costs associated with consultants (e.g. consultant fees/honoraria, per diem, and teleconferences) when their services are required by the Enrichment Program.

Travel: Travel funds to support visiting scientists under the auspices of the Enrichment Program may be requested as well as funds to support Center member travel for special programs. Also, limited travel support may be requested to allow DDRCC investigators to present scientific findings, to learn new laboratory techniques, to develop new collaborations, or to engage in scientific information exchange.

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 (Enrichment Program)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state the aims of the Enrichment Program.

Research Strategy: Describe plans for the Enrichment program in as much detail as possible, including anticipated benefits to Center members and how the program will assist investigators, trainees, and junior faculty to accomplish the goals of the DDRCC.

The Enrichment program will typically support seminars, workshops, research and career development forums, mini-sabbaticals, etc., but any appropriate, innovative means to support the goals of the DDRCC may be proposed. Creative new programs and approaches, not precluded by NIH or NIDDK policies, are encouraged.

While DDRCCs cannot support stipends for postdoctoral fellows, the environment fostered by the existence of the Center with its core facilities in conjunction with the Enrichment Program educational opportunities should serve to foster the careers of postdoctoral fellows and junior faculty, including K-awardees.

Collaborations with other DDRCCs that benefit the DDRCC's Enrichment Program are allowable and encouraged. However, they are optional. Any plans to work with one or more other established DDRCCs may be provided and documented along with a description of the benefit(s) to the Center being proposed. Benefits might include, but are not limited to, cost savings or an augmented Enrichment Program activity. Likewise, collaborations with other Core Centers supported by other NIDDK Center Programs are also encouraged and may also be documented and described.

For renewal applications: Describe the existing Enrichment Program, including its value to the DDRCC members and how the program has been adapted to the needs of the members. Describe future plans for the Enrichment Program.

Letters of Support: Supporting letters related to collaborative interactions with other enrichment activities inside or outside of the DDRCC institution may be provided, as appropriate.

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.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Enrichment Program)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applications must include annual milestones. Applications that fail to include annual milestones will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular Notice of Funding Opportunity (NOFO), note the following:

Reviewers will be asked to evaluate the following individual sections. The overall impact score is not the average for these components.

1. Research base, including the focus on a theme area within the primary mission of NIDDK, quality of research, collaborations among members, relevance to the Center's stated research focus, and, for renewal applications, the maintenance, growth, re-focusing, or evolution of the research base. The research base of a renewal application is not required to have grown since the previous competing award and may have even decreased. The lack of growth or a slight decrease might be viewed positively when it is the result of a concerted effort to enhance the Center's focus. In other words, there could be instances where other considerations such as increased focus of the research base justify the lack of growth or slight decrease in the size of the base.
2. Each Biomedical Research Core, as well as the Clinical Component (if requested), including the documented need for the proposed services; number of users; qualifications of personnel; management, including prioritization and responsiveness to the needs of the users; quality control management; and any appropriate developmental work.
3. The Administrative Core, including committee structure, Center membership criteria, and lines of communication.
4. Pilot and Feasibility Program, including the Program's vision/mission statement and the organization of the overall process of solicitation, review, selection, and monitoring of P and F Projects, and, for renewal applications, the quality, appropriateness and outcomes of supported P and F Projects. The Named Supported Investigator, if applicable, will also enter into this evaluation.
5. The Enrichment Program, including the quality of proposed activities and the likelihood of promoting new scientific collaborations and directions/approaches.
6. Center Director (PD/PI), including leadership and commitment to the stated goals of the DDRCC.

Center Pilot and Feasibility Programs have the option to support Clinical Trials.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Significance

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

Specific to this NOFO: What are the strengths of the Center's research base (its breadth and depth)? How appropriately do the focus, relevance, interrelationships, quality, productivity, and, to some extent, quantity of the research base support the stated theme of the Center? How effectively does the size of the research base strike a balance between having an appropriate number of investigators to justify a Center and maintaining a cohesive focus on digestive and/or liver diseases research aligned with the mission of NIDDK? To what extent will the Center members benefit from the services/programs supported by the DDRCC? What is the likelihood that the DDRCC will increase efficiency; promote new research directions and meaningful collaborations among center investigators; facilitate interactions and collaborations among the investigators; and prove cost-effective? If collaborations with other DDRCCs or individuals outside of the research base are described, how do they benefit the Center? For example, do they enhance the productivity or quality of the research base; enhance the services offered by the DDRCC; expand the diversity of perspectives within the Center; strengthen the Enrichment Program; allow for a more efficient use of the DDRCC's available resources; or otherwise benefit the research base? To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

Specific to this NOFO: How effectively do the Center investigators responsible for the individual research projects interact with each other and contribute to the overall objectives of the DDRCC? How appropriate are the Center Director's and Associate Director(s)' administrative abilities and scientific expertise for effective management of the DDRCC? How strong is their commitment and their ability to devote adequate time for the effective management of the DDRCC? How well qualified are the Core Directors and how appropriate are their scientific expertise and administrative abilities? How well are the P and F applicants prepared to lead their proposed P and F Projects effectively? Do they have the appropriate conceptual and technical expertise for executing the proposed research? The qualifications and potential for each candidate should be evaluated in the context of the candidate's career stage. For a P and F applicant who is a New Investigator, evaluate their training and experience to date as well as their potential for a successful career in digestive and/or liver diseases research. For a P and F applicant who is an established investigator, evaluate their expertise and their past contributions to science as well as their potential to make future contributions to digestive and/or liver diseases research. If requested, how well qualified and appropriate for support is the Named Supported Investigator? To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Specific to this NOFO: How successfully does the Center appear to encourage innovative ideas through their P and F Program? To what extent do the Cores provide new methods, techniques, and/or resources and demonstrate the ability to adapt when needed to support investigators in emerging areas of digestive and/or liver diseases research, as appropriate to the purpose of the Core and the research supported by the Center? To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO: How appropriate and relevant are the proposed Cores and their modes of operation (such as prioritization of requests for services)? To what extent will the Cores benefit the investigators by providing opportunities not otherwise available to the investigators; providing cost savings/cost sharing advantage; and stimulating the development of new approaches? How clear and appropriate are the criteria for membership in the DDRCC? How efficient and effective is the use and/or planned use of the limited enrichment funds, including the contribution of these activities to the stated goals of the DDRCC? How appropriate is the administrative organization proposed for the following:

(a) coordination of ongoing research between the separately funded projects and the DDRCC, including mechanisms for internal monitoring;
(b) establishment and maintenance of internal communication and cooperation among the Center investigators;
(c) mechanism for selecting and replacing professional or technical personnel within the Cores;
(d) management capabilities, including fiscal administration, procurement, property and personnel management, planning, budgeting, and other appropriate capabilities?

How well does the P and F Program's vision or mission statement reflect the overall Center's goals and inform the Program's processes? How appropriate and transparent are the processes for soliciting, evaluating, and selecting the P and F projects? Does the solicitation process reach the appropriate pool of potential candidates? Are the evaluation and selection processes free of bias and likely to lead to awards for strong applications?

Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

Specific to this NOFO:How supportive is the institutional commitment to the Center program's management and scientific impact? How strong is the potential for scientific interactions? To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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.

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 NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). 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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Prior Approval of Pilot Projects

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690)) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. Awardees will provide updates at least annually on implementation of the PEDP.

Progress reports should briefly describe status of pilot projects, including data and safety monitoring, and should notify NIH of serious adverse events and unanticipated problems.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Peter J. Perrin, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-3759
Email: [email protected]

Jian Yang, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)
Telephone: 301-594-7637
Email: [email protected]

Kaitaia Fu
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-6785
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.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.