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 instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Knowledgebases that maintain deeply curated datasets, and allow users to access, reuse and integrate such resources, have become critical enablers for biomedical research. In addition, because of the complexity of biological systems, the research community is increasingly dependent on knowledge stored in computable forms, as exemplified by knowledgebases of ontology, pathways, interactomes, and other domain-specific ---processed information. Furthermore, modern knowledgebases employ advanced data science technologies such as semantic technology, Natural Language Processing (NLP), and Artificial Intelligence and Machine Learning (AI/ML). These advances have increased knowledgebase efficiency, scalability and interoperability, and make them essential resources for the research community at large.

In the past decade the research community has generated a growing collection of high-quality heterogenous data types describing human pancreata collected from both normal healthy donors and donors living with diabetes. Contributors to this acceleration in data collection include consortia belonging to the Human Islet Research Network (HIRN) and its Human Pancreas Analysis Program (HPAP), and several other NIDDK-supported programs including the Integrated Islet Distribution Program (IIDP). Relevant data are also being generated by programs supported by other agencies, such as The Network for Pancreatic Organ Donors with Diabetes (nPOD) that is supported by the Juvenile Diabetes Research Foundation (JDRF) and the Helmsley Charitable Trust; as well as from individual investigators. These complex datasets are a rich source of (largely hidden) high resolution, high depth information about the molecular and cellular composition of the pancreatic islet cellular environment, the way cell types and subtypes interact in this environment, and the events regulating basic pancreatic function and dysfunction. Although data repositories already exist (such as the PancDB, Pancreatlas), much of the data remains extremely under-interrogated.

In addition to the datasets, the diabetes research community has also accumulated extensive, though often fragmented, processed information about the pancreatic islet niche in healthy and diabetic individuals. This includes knowledge about cell types and molecules, signaling pathways and regulatory programs, as well as the molecular interaction networks and tissue cross talk that are involved in disease pathogenesis. While such knowledge remains largely scattered in the literature, it is possible that once retrieved, compiled, and curated into machine-readable and actionable forms, they may be integrated to formulate novel hypotheses and theories, and incorporated to guide new approaches to data analysis and modeling.

To facilitate utilization and integration of important data and knowledge, and foster innovations within the diabetes research community, a centralized resource focused on the human pancreas that will provide openly accessible, high-quality deeply-curated data, computable knowledge, and advanced analytical tools is needed. Such a resource will enable bench molecular biologists to analyze, visualize and interpret their research results; data scientists and bioinformaticians to develop novel approaches for data mining and knowledge discovery; and systems biologists to build predictive mechanistic models of normal and disease pathways for biomarker and drug target discovery.

Scope and Objectives

This initiative will support the creation of a human Pancreas KnowledgeBase (PanKbase) program. The overarching goals of the program will include: meeting community needs for accessing essential data, knowledge and tools; fostering cross-disciplinary collaborations; promoting Rigor and Reproducibility (R&R) in research; and driving innovation, discovery and paradigm shifts toward biomarker and therapeutic target development. The program will play a key role in organizing, representing, standardizing and disseminating data and resources focused on the human pancreas. PanKbase will become a new component of the Human Islet Research Network or HIRN (https://hirnetwork.org/).

The program will be led by a Multi-PD/PI team that seeks to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to domain knowledge and experimental designs. The leadership will include at least one computational biologist and one islet biologist with extensive experience of human Type 1 Diabetes (T1D) pathogenesis. The team should have a demonstrated track record of developing community resources such as biomedical data repositories and knowledge portals, expertise in modern data science technologies and platforms; deep appreciation of the important research questions in diabetes especially in T1D; and experience in outreach to research communities by effectively communicating and engaging with scientists from diverse backgrounds.

More specifically, the program will be responsible for developing and maintaining a centralized, openly accessible, comprehensive resource of the human pancreas for the diabetes research community, with the following major components.

Database

This component will assemble and maintain a core set of deeply curated and annotated high-quality data and meta data of the human pancreas, from both normal donors and donors with diabetes at various stages of the disease, with a primary focus on Type 1 Diabetes (T1D). Anticipated data types will include multi-omics data, spatial omics and single cell data, deep phenotyping, imaging, physiological and functional measurements, and clinical information about tissue donors.

It will define and maintain cellular atlases and molecular signatures of major cell types found in the human pancreas at different stages of T1D, from normal to stage 3. These will include cell types from all relevant tissue compartments (including endocrine, exocrine, ductal, immune, vascular and neuronal). Efforts to define the human pancreas- and diabetes-specific atlases and signatures will maximally leverage other, more broadly-focused, efforts, including the NIH common fund programs such as the Human BioMolecular Atlas Program (HuBMAP), the Cellular Senescence Network (SenNet) Program, international community efforts such as the Human Cell Atlas program, and the benchmarks that they have developed such as the Tabula Sapiens, to help define normal references.

This component will assemble and maintain a collection of domain knowledge in computable forms, such as curated pancreas cell-specific and T1D-specific gene and protein networks, protein complexes, pathways and interactomes; as well as other knowledge of human pancreas structure, function and physiology. It will maximally leverage existing general-purposed knowledgebases of pathways and interactomes (such the KEGG pathway database, the Gene Ontology, and the Reactome). These programs typically focus on molecular relationships shared across most human tissues, under a range of different physiological and pathological conditions, which can serve as normal references.

This component will also include an internal reference database that consolidates information from external data repositories where relevant exiting datasets are housed. It will maintain data types harmonized, interoperable, and ready for AI/ML applications.

A library of analytics

Analytical tools that are relevant to the utilization, integration and interrogation of the core PanKbase datasets and computable knowledge, will be collected and hosted. These can include (but are not limited to) tools for knowledge extraction from data, deep curation and annotation of data, integrated analysis of complex and heterogeneous data sets, representations of scientific concepts, and creative tools for visualization and reporting. The library will maintain dynamic links to software tools repositories such as GitHub and Bioconductor, and will maximally leverage and reuse existing tools.

The library will also develop, host, and share advanced data modeling workflows for predictive and mechanistic modeling of novel biological insights and new testable hypotheses using PanKbase datasets. Initially it will focus on use case workflows that are designed to answer research questions regarding T1D initiation. Examples include but are not limited to: the triggering events of -cell destruction in T1D; the perpetuating nature of disease initiation and progression; the interactions and cross talks between cells in the islet tissue niche, including endocrine, immune, and other cell types; the interplay between pro-inflammatory and immune regulatory pathways; and the immune checkpoints. Answers to these questions are important for developing next-generation biomarkers, including composite biomarkers, that catch the initiation and early progression of disease, and for developing effective prevention and early therapeutic interventions.

An open science platform

The platform will allow users to query, annotate, aggregate, visualize, and integrate data and knowledge from PanKbase’s database and library, through a user-friendly web interface. It will allow investigators to select and combine datasets of interest, assemble data analysis workflows using embed tools from its library, customize the tools and the workflows if needed, run analysis, and save and share their analysis instances. The PanKbase will maintain an inventory of analysis results of its datasets. Others can potentially rerun the same exact analysis of the same dataset, and reproduce the findings; or adopt/modify the workflow for new analysis.

PanKbase will take advantage of modern data science technologies to enhance performance and improve efficiency; to provide the knowledgebase content in novel ways that are informative, efficient, and intuitive to users; and to ensure that the platform will scale efficiently and sustainably with both the growing data volume and complexity. Such technologies can include but are not limited to, natural language processing (NLP), semantic technology, Artificial Intelligence and Machine learning (AI/ML), and Deep Learning (DL).

The platform will be in cloud and friendly for AI/ML applications. The knowledgebase will use community standards and ontologies for data, metadata and tools, and include a scheme to assign persistent unique identifiers to track all resources, and to promote sharing, FAIR practice, and R&R.

Community & stakeholder outreach and engagement

The diabetes research community and stakeholders will be engaged to contribute domain knowledge, data, and analytical tools and workflows, and to participate in curation and annotation. Additionally, the community will be recruited to assist in deciding the scope, functional features, standards and performance metrics of PanKbase. A NIDDK research community-based scientific advisory board will be formed, to ensure knowledgebase performance in meeting defined needs. While plans to invite and support sub-awards that may augment program outreach or collaborative functions, including the recruitment of community contribution, are not requested in this funding opportunity announcement, additional funds may be made available at a later time to support and expand these types of collaborative activities.

Partnerships with other NIDDK funded programs.

PanKbase will work closely with the other programs and the research consortia of the HIRN, most importantly, the Research Enhancement Center (HIREC), and the Human Pancreas Analysis Program (HPAP). These partnerships will be important for data compilation, curation and annotation, and meta data development; for collecting and curating domain knowledge; and for testing and validating novel predictions coming out of collaborations and data analyses enabled by PanKbase. PanKbase will collaborate with other NIDDK programs that may host data types of, or related to, normal and disease human pancreas, such as the IIDP, the Environmental Determinants of Diabetes in the Young (TEDDY) and the Accelerating Medicines Partnership-Common Metabolic Diseases (AMP-CMD) knowledge portal. Other programs to collaborate with may also include the NIDDK information network (dkNET). PanKbase may work with dkNET on tracking and sharing data and resources, development of persistent unique identifiers for digital objects, community outreach and engagement, workforce development, and FAIR and R&R.

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

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 FOA.

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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 full SAM and Grants.gov registrations; 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.

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.

The application is required to be submitted as a multiple PD/PI application with a minimum of 2 PDs/PIs, all of whom must have an appointment at a domestic institution. The contact PI should be a computational biologist, and the research team should include one islet biologist with extensive experience in human type 1 diabetes pathogenesis as a MPI. Scientists employed solely by foreign institutions may not serve as one of the PD(s)/PIs of the multiple PD/PI team, although they may be included in the application as collaborators/co-investigators, consultants or other significant contributors. Visit the multiple PD/PI Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide, and the Grant Policy Statement on Multiple Principal Investigators. Minimum allowed efforts by the PDs/PIs are described in the R&R Budget instructions in Part 2. Section IV.2.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 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 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, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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 F. Connaughton, Ph.D.

Chief, Scientific Review Branch

National Institute of Diabetes and Digestive and Kidney Diseases
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 Application Submission

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Cover

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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 and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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.

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

Research Strategy: Applications should clearly describe:

• A brief description of the multidisciplinaryPD/PI team and the expertise that each team member will bring to the project (without duplicating information contained in the biosketches), and how collaborations between them will bring together scientific expertise needed to develop a useful and impactful knowledgebase.
• The team’s vision of the program, and the designing principles of the knowledgebase.
• Feasible plans for all major components of the knowledgebase.
• Plans for integrating advanced data science technologies to enhance performance, reduce cost, and to ensure scalability and sustainability of the knowledgebase.
• New and novel strategies for open science and cloud-computing.
• Strategies to engage the community; and plans for supporting the user community, including documentation, training, and other outreach activities
• Plans to partner with other HIRN, and other NIDDK-funded programs and research consortia.
• Plans for participating in HIRN activities, including annual meetings and working groups, as well as education and outreach activities.
• Plans to support the FAIR data principles, to enhance R&R.
• A timeline and a list of yearly milestones for achieving the project goals.
• A plan for long-term sustainment of the knowledgebase

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:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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" (https://cde.nlm.nih.gov/home)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.

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.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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.

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.

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.

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.

2. Review and Selection Process

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

• 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 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 FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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.

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

2. Administrative and National Policy Requirements

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

• Federalwide Research Terms and Conditions
• 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 must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html 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 FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, 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 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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement U24, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Recipients will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• The Principal Investigator/Program Director will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations, and policies.
• The recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current HHS, PHS, and NIH policies.
• All staff of the recipients will maintain the confidentiality of the information developed by the investigations, including, without limitation, study protocols, data analysis, conclusions, as well as any confidential information received by third party collaborators.
• All staff of the recipients will be required to participate in a cooperative and interactive manner with NIH staff.
• Recipients will submit a list of milestones and project deliverables to the NIDDK.
• Recipients must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
• Recipients must share data, tools, models, methods, information, and unique research resources that are generated by the projects in concordance with NIH and NIDDK policies. Awardees will be expected to collaborate; share novel findings, methods and models and resources; and share both positive and negative results that would help guide the research activities of other consortium members.
• Recipients agree to establish agreements amongst themselves that address the following issues as appropriate and consistent with achieving the goals of this program:
• • Procedures for data sharing among consortium members and data sharing with industry partners;
  • Procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators;
  • Procedures for addressing ownership of intellectual property that result from aggregate multi-party data; and
  • Procedures for reviewing publications, determining authorship, and industry access to publications.
• Recipients agree that each industry collaboration should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures.
• Any third-party collaboration (including but not limited to interactions with organizations from industry, academia, and nonprofit institutions) should be governed by a research collaboration agreement (e.g., Clinical Trial Agreement, Research Collaborative Agreement, etc.) or any third-party contract mechanism(s) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network studies between grantee and third-party will be provided to the NIDDK Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network policies. Further, at the request of the NIDDK Program staff, any other network-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions , and Section 8.5.2, titled: Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support , noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.
• Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and network activities that includes access to any network generated resources (i.e., data and biosamples), or study results that are not publicly available, or using the name of the network or study or the name of the NIH or NIDDK,ispermitted onlyafter written permissionby the NIDDK Program staffwho will consultwith others at NIH and NIDDK Technology Advancement Office.
• Recipients agree to the governance of the study through a Steering Committee:
  • The Steering Committee will be composed of the following voting members: PD(s)/PI(s) representing the U24 awards; and an NIDDK Project Scientist
  • The PD(s)/PI(s) will attend all meetings of the Steering Committee
  • Each full member will have one vote.
  • Recipients will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees.
  • Recipients must serve on subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator’s Retreat.
• Recipients may be asked to scientifically review applications for special opportunity pool funds, as it is deemed appropriate.
• In accordance with the NIH Policy for Data Management and Sharing (NIH NOT-OD-21-013), the NIDDK approved plan will become a term and condition of award, be routinely monitored during the award period, and compliance may factor into future funding decisions. Upon completion or termination of the research project(s), the recipients are responsible for making all data, tools, products, and resources broadly available and making them accessible to the research community according to the NIH-approved data sharing and dissemination plan. This should be accomplished on timely manner and no later than the end of the study. Recipients may not continue to use or share study generated resources until those resources are available to the public via an NIDDK approved repository per the NIDDK approved sharing plan.

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

• The NIDDK will designate program staff, including a Program Officer and a Grants Management Specialist, to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.
• An NIDDK Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIDDK Program Official as follows:
  • The NIH Project Scientist will coordinate and facilitate the research projects, participate in the bi-monthly call, attend the site visit, and act as a liaison between the Recipient and the External Experts.
  • The NIH Project Scientist and Program Officer will review the scientific progress, cooperation in carrying out research, and maintenance of high quality research, and review the project for compliance with the stated goals and objective of this FOA. Based on this review, the Project Scientist in conjunction with the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of scientific progress or adherence to the objectives and goals of this FOA. Review of progress may include regular communications between the Principal Investigator/Program Director and NIH staff, additional site visits for discussions with recipient research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
• The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach, (2) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, or (3) concerns related to human subject safety that prompt the need for premature termination.
• The NIH may enlist additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist in carrying out the goals and aims of the approved studies.
• The NIH Project Scientist will have substantial scientific programmatic involvement in research coordination and performance monitoring. The dominant role and primary responsibility for these activities resides with the recipient; however, specific tasks and activities in carrying out the studies will be shared among the awardees and the NIH Project Scientist.
• The NIH Project Scientist serves as a resource with respect to facilitate interaction with other ongoing NIH activities.
• The NIH Project Scientist or designee may coordinate activities among recipients by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data and in the publication of results.
• The NIH Project Scientist may review procedures for assessing data quality and monitor study performance.
• The NIH Project Scientist may be a co-author on study publications. In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results; and (d) preparation and authorship of pertinent manuscripts.

Areas of Joint Responsibility include:

After the award an initial face-to-face meeting between the Project Scientist, other relevant NIH staff, and the recipients will be scheduled. This meeting will have the main purpose of jumpstarting the project and evaluating and modifying as necessary the proposed milestones.

Expert Scientific Panel (ESP)

An independent panel of three to five scientific experts (ESP) will be appointed by the HIRN steering committee, and meet at least once a year. The PanKbase-ESP will be updated on progress and give feedback to the HIRN Steering Committee on adjustments and future directions.

Dispute Resolution

Disagreements that may arise in scientific/technical matter or programmatic matters (within the scope of the award) between award recipients and the NIDDK may be brought to arbitration. The arbitration panel will be composed of the Principal Investigator, one NIH designee, and a third designee from the independent panel of review experts. This special dispute resolution procedures in no way affect the recipient's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

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.

3. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 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: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Xujing Wang

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Telephone: 301-451-2862
Email: xujing.wang@mail.nih.gov

Ann A. Jerkins, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2242
Email:[email protected]

Craig Bagdon

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

301-594-2115

[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.