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 How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



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

This is a non-competitive funding opportunity intended to fund a single award.  The NIDDK is announcing its intent to issue a single source cooperative agreement award to the University of Pennsylvania to continue the mission of the existing Human Pancreas Analysis Program for Type-1 Diabetes (HPAP-T1D). This NOFO will support one team of investigators with combined expertise in human pancreas physiology and pathophysiology; immunology and autoimmunity; collection, processing and multimodal analysis of human pancreatic tissues and immune compartments; and biological database building, curation and management, that will be tasked to: 1) identify, collect and intensively characterize primary pancreatic tissues and immune cells from patients with Type 1 Diabetes (T1D) or at risk of developing the disease, as well as age-matched controls; and 2) analyze, organize and share the data resulting from the study of these tissues through the existing PANC DB open-access resource database.  HPAP-T1D is a component of the Human Islet Research Network or HIRN. HIRN was created in 2014 to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional human beta cell mass. 

Background

Much remains to be learned about the causes and triggers of T1D in humans. A detailed description of the series of events that leads to beta cell dysfunction and loss in human pancreatic tissues, particularly during the asymptomatic phase of human T1D, could help identify biomarkers highly specific for early T1D, and design therapeutic strategies to delay or stop the progression towards clinically overt T1D by slowing or preventing the development of beta cell-specific autoimmunity.

While it is now possible to identify individuals at highest risk for developing T1D prior to clinical manifestations, it remains a difficult disease to investigate given our inability to access the target organ in living individuals. In recent years, several tissue procurement programs have facilitated access to pancreatic tissues or human islets from cadaver donors. The NIDDK-supported Integrated Islet Distribution Program or IIDP (https://iidp.coh.org/Overview) provides dissociated human islets to investigators, although it does not currently distribute dissociated islets from T1D donors. The JDRF-supported Network for Pancreatic Donors with Diabetes or nPOD (https://www.jdrfnpod.org/) is procuring pancreata and related tissues from organ donors with T1D as well as those who are islet autoantibody positive. While these tissue-procurement programs have contributed significantly to increase our understanding of T1D initiation and progression, the amount of high-resolution data generated from human pancreatic tissues that the scientific community can access and use to formulate and test new hypotheses remains limited. The reasons for the paucity of cellular and molecular information related to the human pancreatic tissue environment include the following:

• Most published studies performed on human pancreata or human islets do not provide links to the in-depth clinical histories of the donors, or detailed information about how the tissue was collected and processed post-mortem;
• Most basic research experiments on human pancreata examine either pancreatic sections or isolated islets, but rarely both from the same donor;
• Most of the protocols used for collecting and fixing human pancreatic specimens (to be shared with the investigator community) in ways that are compatible with state-of-the-art molecular techniques are still under development and not widely standardized;
• Most of the research on human pancreatic tissues or isolated islets consists of independent investigations performed by individual research groups applying a limited set of technologies and non-standardized protocols to test a specific scientific hypothesis;

A systematic, comprehensive, unbiased and standardized deep phenotyping (molecular, anatomical and functional) of human pancreata at various stages of disease development, from the early signs of autoimmunity to the overt clinical disease, would provide a thorough understanding of the mechanisms contributing to disease development and progression throughout the natural history of disease and would greatly facilitate our understanding of the origins and diversity of human T1D . To complement the body of knowledge resulting from investigator-initiated studies and facilitated by existing tissue-distribution programs, NIDDK created in 2016 the Human Pancreas Analysis Program (HPAP) as a resource-generation and data-analysis component of the Human Islet Research Network or HIRN (RFA-DK-15-027). The program was renewed in 2021 (RFA-DK-20-016) and renamed HPAP-T1D. The mission of the HPAP-T1D (https://hirnetwork.org/consortium/hpap) is to systematically apply a suite of standardized technologies with single-cell resolution to fixed pancreatic tissues and live cells, and to combine these measurements with a series of functional assays to obtain a high-resolution and extensive phenotyping of the human endocrine pancreas and its interaction with the immune system for each and all tissue specimens being analyzed. The high-value datasets resulting from this phenotyping effort are shared with the research community as soon as generated and quality-controlled through a searchable database called PANC DB (https://hpap.pmacs.upenn.edu/ ). It is expected that HPAP-T1D datasets will be mined and analyzed in creative ways by the research community to generate hypotheses with regard to disease pathogenesis that can then be tested on human cells and tissues made available by distribution programs such as nPOD or the IIDP, or through clinical studies. HPAP-T1D is supported by the Special Statutory Funding Program for Type 1 Diabetes Research (Special Diabetes Program). A companion effort called HPAP-T2D was launched by NIDDK in 2019 (via RFA-DK-18-016, https://grants.nih.gov/grants/guide/rfa-files/rfa-dk-18-016.html), with the mission of expanding the operational scope of the HPAP to the study of pancreata recovered from tissue donors with Type 2 Diabetes (T2D) and related metabolic disorders. HPAP-T2D is also part of the HIRN effort, uses most of the HPAP-T1D technology suite for data-generation, and shares the resulting datasets with the scientific community through PANC DB.

This NOFO will support the renewal and continuation of the HPAP-T1D effort. While the overall scope of HPAP-T1D remains the same, the renewal application should take into account the following guiding principles:

• Continuity in data collection and data standards: After six years of operation, HPAP-T1D has yielded important new insights into the pathogenesis of T1D, following analysis of the HPAP-T1D data by both HPAP and non-HPAP investigators. A key to this success is a rigorous and standardized operational workflow, from human tissue procurement and processing to the multimodal single-cell analysis of various pancreatic compartments. Each assay contributing to the functional and molecular phenotyping of these tissues is performed by a single team of investigators and technicians, minimizing the risk for noise and variability in data production. The large majority of the HPAP-T1D data-collection, data-curation and data-sharing through the PANC DB open-access resource database is led by the HPAP-T1D team at the University of Pennsylvania. The need for continuity in data-generation processes is the primary reason and main rationale as to why NIDDK seeks a single renewal application from the existing HPAP-T1D team, and why we ask the team to introduce only minimal changes as possible to the legacy protocols and data standards used in the previous funding period.
• Technological improvements: while continuity in the data-generation process and workflow is critical to maintain data homogeneity and to facilitate future cross-analysis of old and new datasets, taking advantage of powerful emerging technologies should also be a priority of the HPAP-T1D effort, and the renewal proposal should strike a balance between continuity and innovation. In the context of a limited budget, introducing new technologies may come at the price of retiring less informative legacy assays. 

Research Goals and Objectives

Through this renewal, the HPAP-T1D team will build upon the progress made by the HPAP-T1D during its prior funding cycles with minimal disturbances to the existing data-generation workflow, and with introducing technological innovations only when these can result in a significant deepening of the HPAP-T1D pancreatic tissue phenotyping effort. At a minimum, HPAP-T1D investigators need to articulate how they will perform the following required tasks in the renewal proposal:

 1) Assemble and phenotype a diverse collection of human pancreata and immune cell samples relevant to T1D pathogenesis:

HPAP-T1D should propose and implement a strategy for identifying and collecting human pancreatic specimens from donors with stage 1 and stage 2 T1D, recently-diagnosed T1D, established T1D or other physiological conditions affecting pancreatic beta cell mass or function, as well as from age-matched healthy donors.  HPAP-T1D should establish criteria for inclusion/exclusion of tissues into the HPAP-T1D collection with the goal of generating datasets that reveal unique aspects of pancreatic function/dysfunction associated with the development and/or heterogeneity of T1D. At a minimum, the HPAP-T1D team should describe how they intend to:

• Identify, coordinate and manage tissue source sites to acquire human pancreata from cadaver donors that are relevant to the mission of HPAP-T1D. The applicant should describe their strategy to identify and characterize donors with early stage T1D or recent onset clinical T1D using measurements such as islet cell autoantibodies. The tissue source sites would be responsible for skilled and expedited autopsy, sample acquisition and processing, preservation, as well as collection and completion of proper documents, including consents. HPAP-T1D should ensure that the human sample collection and handling procedures comply with current NIH policies; 
• Collect as much of the de-identified medical records of the donors as possible, to include whenever possible, the following: donor age, sex, race, Body Mass Index (BMI), ABO blood group, Rh blood type, cause of death, cardiac arrest downtime, cardiopulmonary resuscitation time, admission and cross clamp date and time, cold ischemia time, intraoperative time for pancreas recovery, pancreas weight, serum C-peptide level, HbA_1c, T1D autoantibody status, infectious disease serology, prior clinical diagnoses (e.g., diabetes, cancer, coronary artery disease, other autoimmune disease), clinical interventions during terminal hospital visit, family medical history, and diabetes duration. At a minimum, all the information currently collected by the HPAP-T1D team on each and every tissue donor should continue to be provided and shared through PANC DB under the formatted “Donor Summary” tab;
• Process pancreata using protocols that allow for multiple analytical paradigms to be performed on the same specimen, including functional studies on subsets of live islets, sorted endocrine and immune cells, and a variety of molecular studies on fixed tissue. Ideally, this fine-processing step should be performed by the current surgery team at the U Penn location, to minimize output variability. The creation of an alternative tissue isolation center with identical surgical and tissue-processing protocols could be considered to help manage tissue donation opportunities emerging outside the upper East Coast of the United States, from where the bulk of HPAP-T1D donor tissues are currently originating. The proposed tissue-processing strategy should closely mimic the current HPAP-T1D protocols for systematic isolation of live islets from part of the tissue (to be used for functional studies of islets and transcriptomics analyses on sorted islet and immune cell populations) and fixation of the rest of the specimen using a variety of procedures to allow for multiplexed analyses using antibody-based, in-situ hybridization experimentss and multi-omics analyses with single-cell resolution. Immune cells should be isolated from the pancreatic tissue and its associated lymphoid organs, including the peri-islet compartment and individual lymph nodes, as currently performed ;
• Define and run a standard set of deep phenotyping experiments (molecular, functional and anatomical) to create reference datasets for each and every HPAP-T1D specimen. At a minimum, these experiments should include the major analyses currently being run within HPAP-T1D to ensure consistency and continuity between the datasets generated before and following the current initiative. The list of assays systematically run by HPAP-T1D are documented on the PANC DB community portal (https://hpap.pmacs.upenn.edu/#research ) and includes: experiments in histology (histological sectioning and staining), islet cell sequencing (RNAseq, ATACseq and whole genome bisulfite sequencing), islet physiology (calcium imaging, electrophysiology, oxygen consumption, perifusion studies for insulin and glucagon), mass cytometry (flow cytometry and imaging mass cytometry), B lymphocyte cell studies (autoantibody analysis, immunophenotyping and B-cell receptor sequencing), T lymphocyte cell studies (immunophenotyping, gene expression, cytokine secretion, T cell sequencing) and T regulatory cell studies (Treg suppression).
• Add powerful new technologies to the suite of existing HPAP-T1D phenotypic assays. An example could be the adoption of spatial omics measurements to perform imaging-based identification of large numbers of transcripts and  protein species through a single experiment with single cell resolution. Such a technology would allow the molecular characterization of every single cell present in a given pancreatic tissue slice, together with in-depth description of each cell's tissue environment, thereby greatly enhancing the kind of cell-based information currently available in PANC DB. Ideally, the chosen protocol would allow for the retrospective analysis of stored HPAP-T1D samples to optimize the phenotyping impact across the entire HPAP-T1D sample collection. The cost of developing and implementing such a new protocol could be offset by dropping legacy assays that are deemed redundant or less informative than the newer technology, such as the currently used Imaging Mass Cytometry and CODEX protocols.
• Catalog, annotate and store all residual (unused) pancreatic tissues and cells with methods that preserve bio-specimen integrity and will allow future experiments to complement the standard suite of phenotyping analyses.

2) Maintain and grow T1D-relevant datasets:

The HPAP-T1D team should continue to organize and integrate all functional, anatomical and molecular data and metadata generated from the HPAP-T1D tissue analyses into the  community database PANC DB (https://hpap.pmacs.upenn.edu/ ) that enables the scientific community to explore important aspects of pancreatic function and dysfunction associated with both T1D (HPAP-T1D datasets) and T2D (HPAP-T2D datasets). The overall organization of the database, as well as its analysis and visualization tools, should continue to facilitate the exploration of 3D structural and functional relationships at the cellular and organ-wide level, generating mechanistic hypotheses related to T1D pathogenesis or the disease diversity in the human population, or identifying novel candidate drug targets. In order to fulfill this function in the years to come the HPAP-T1D computational biology team  should continue at a minimum to support the following functions:

• Share datasets with the research community as soon as they are generated and quality-controlled;
• Develop and improve tools and protocols to efficiently extract, curate and incorporate all data resulting from the study of HPAP-T1D tissues into PANC DB. The database should be flexible and extensible to manage and integrate multiple types of data, including clinical data, data resulting from physiological assays, genomics, proteomics and metabolomics data and imaging-based data. The data should also be interoperable with other related databases;
• Take advantage of recent development and rapid advances in artificial intelligence (AI) to rethink the way HPAP-T1D data could be analyzed and made AI-ready;
• Improve analysis tools for data integration, including for the co-registration of data of disparate but complementary nature (anatomical/spatial, functional and multiple omics);
• Maintain and enhance the PANC DB open-access portal with user-friendly interfaces to allow the research community easy access to the data;
• Continue to develop/adapt and share tools for on-line data mining, image analysis and visualization of data and metadata by the research community; 
• Work closely with the user community to build or make available any additional tool or feature that can facilitate the deposition, archiving, extraction, analysis or visualization of data;
• Assist HIRN investigators and the wider research community in accessing and analyzing HPAP-T1D datasets through presentations, webinars, tutorials and hands-on workshops;
• Advertise HPAP-T1D’s activities and resources to the scientific community worldwide through publications and presentations at international meetings;
• Ensure that datasets and documentation are in a widely-adopted “standard format” for continuing data accessibility and data interoperability beyond the close out of the project

3) Forge partnerships with relevant investigator communities and research programs:

HPAP-T1D will be responsible for leveraging the activities of relevant programs through the formation of strategic partnerships with existing efforts related to its mission. Such partners should include at least the following:

• HPAP-T2D investigators: the HPAP-T1D team should work closely with HPAP-T2D investigators to ensure standardization of tissue processing, data-generation and data format to facilitate integration and interoperability of all HPAP-generated datasets into the common PANC DB database.
• HIRN investigators: the HPAP-T1D program will continue to be part of the NIDDK-supported HIRN, whose overall mission is to better understand how human beta cells are lost in T1D, and to find innovative strategies to protect or replace functional beta cell mass in diabetic patients. The HPAP-T1D team will join the HPAP-T2D team and a group of investigators funded in response to the recent RFA on “High-Resolution Exploration of the Human Islet Tissue Environment” ( RFA-DK-21-017) to form the ‘Human Pancreas Analysis Consortium" or HPAC. HPAP-T1D is expected to work closely with the Human Islet Research Enhancement Center (HIREC) to facilitate the organization and sharing of data and reagents generated by HPAP-T1D activities. In conjunction with the HIREC, the HPAP-T1D should develop workshops, webinars and community outreach strategies to optimize community use of HPAP-T1D resources and to gather feedback from users. The HPAP-T1D team will be expected to work collaboratively with all of their HIRN colleagues and to contribute to an environment of sharing and trust across the network. All HPAP-T1D investigators will be expected to adhere to the sharing policies developed by the HIRN as a term of the award and to the Cooperative Agreement Terms and Conditions of Award.  In the application, budget requests must include costs for the PD(s)/PI(s) and up to three other HPAP-T1D staff members to attend the annual HIRN Investigator's Scientific Retreat.
• HIRN PanKbase: the HPAP-T1D team should describe how it plans to interact with the recently-created Pancreas Knowledgebase Program or PanKbase (see RFA-DK-22-018), that will serve as a centralized resource about the human pancreas for diabetes research; will provide access to deeply curated high-quality datasets, knowledge in computable forms, advanced data science tools and workflows; and will enable open and reproducible multidisciplinary collaboration toward accelerating biomarker and therapeutic target development.
• Scientific collaborators: residual HPAP-T1D cells and tissues are and will continue to be in limited supply following the thorough and systematic phenotyping that is the core mission of HPAP-T1D. In addition, the vast amount of data associated with any residual material makes it an even rarer and valuable commodity. For these reasons, the open sharing of residual HPAP-T1D cells and tissues with the broader scientific community is not the best or most efficient way to gather additional and meaningful biological information to complement the extensive analysis performed on each and every HPAP-T1D sample. Rather, the further exploration of these tissues will need to be carefully planned and justified in collaboration with the HPAP-T1D Steering Committee (that includes the HPAP-T1D Project Scientist) to optimize the biological significance and value to the community of any additional experiments. In their renewal application, the HPAP-T1D team should propose guidelines for candidate collaborators to approach the HPAP-T1D Steering Committee to propose additional experiments, whether hypothesis-driven or hypothesis-generating. These guidelines should describe the process by which projects will be prioritized and selected, and should include a mechanism to ensure that all resulting data will be shared with the community through PANC DB.

Other Special Performance Requirements

The HPAP-T1D investigators may be asked to identify fixed and variable costs and establish procedures for negotiation of third party agreements or selection of subcontractors and develop processes to efficiently administer and manage throughout the project.

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 NOFO.

Section III. Eligibility Information

1. Eligible Applicants

 Only the following applicant may apply for this single source funding: University of Pennsylvania. Please refer to Section 1. Notice of Funding Opportunity Information for more details.

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• 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 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.

Only the PD/PIs associated with the award issued under RFA-DK-20-016 to University of Pennsylvania is eligible to apply for this single source funding. Please refer to Section I. Notice of Funding Opportunity Information for more details."

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Only a single award will be issued to University of Pennsylvania under this single source funding opportunity. Please refer to Section I. Notice of Funding Opportunity for more details.

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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - 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: NIDDKLetterofIntent@mail.nih.gov

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed, with the following exceptions:

For this specific NOFO, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply - Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Research Strategy:

HPAP-T1D applicants must include in their research strategy:

• Progress report: a summary of what has been accomplished during the previous funding period, to include information on the use of HPAP-T2D datasets by the non-HPAP research community and on the new biological knowledge that has resulted from the analysis of HPAP-T2D data to date;
• A summary of the proposed tissue-processing, data-generation, data-analysis and data-sharing workflow. At a minimum, most of the phenotypic assays currently run by the HPAP-T1D (as documented on the PANC DB community portal) should be proposed. These include experiments in histology, islet cell sequencing (RNAseq, ATACseq and whole genome bisulfite sequencing), islet physiology (calcium imaging, oxygen consumption, perifusion studies for insulin and glucagon), imaging-based analysis of pancreatic tissues and immune cell studies (including B, T and Treg cells). Applicants are also encouraged to add a limited number of new assays to take advantage of emerging technologies that can significantly enhance HPAP-T1D's phenotyping depth. Such new assays could include state-of-the-art spatial omics platforms for the exploration of pancreatic tissue slices at single cell resolution. The addition of new assays, and the possible elimination of less informative legacy assays to make room for them within the HPAP-T1D budget, should be clearly justified in the application;
• An estimated number of the human pancreatic specimens to be collected and characterized per year of operation and a rationale for the prioritization of tissue donors; 
• A strategy to analyze the data being generated through HPAP-T1D, including the meta-analysis of the multiple datasets being generated through the suite of functional, omics-based and imaging-based phenotypic assays, in order to collect as much new information as possible regarding human disease initiation, progression and heterogeneity. Such a strategy should include the use of artificial intelligence (AI)-based analytical tools;
• A plan to prioritize and manage requests for collaborations by non-HPAP investigators wanting to access residual HPAP-T1D cells and tissues to generate experimental data that would complement HPAP-T1D's own data-generation and data analysis;
• An outreach plan describing how the team will advertise HPAP-T1D activities and facilitate/encourage the use of its datasets;
• A plan to encourage feedback from the user community on how to improve the operability of PANC DB, including its analysis and visualization tools;
• A description of the contribution of each team member to the overall effort. 
• Applicants should also describe how the results from additional experiments conducted on residual (stored) HPAP-T2D samples could be added to the standard datasets and made available to PANC DB users.
• Letters of support: the HPAP-T1D application should identify the tissue source sites and provide supporting letters from these sites to demonstrate capacity and commitment to deliver the types and numbers of human pancreatic specimens described in the grant application, as well as their willingness to assist with the collection of medical information about tissue donors. Applicants are expected to register resources supported by this NOFO with the NIDDK Information Network (dkNET) at https://dknet.org/ and use Research Resource Identifiers (RRID) assigned through dkNET in any publication supported by this NOFO.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide, with the following modifications:

The NIDDK intends the resource sharing plans for the HPAP-T1D to cover protocols (including analytical methods), experimental workflow.This information should be made available through the existing PANC DB open-sharing database.

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.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• Applicants are expected to register resources supported by this NOFO with the NIDDK Information Network (dkNET) at https://dknet.org/ and use Research Resource Identifiers (RRID) assigned through dkNET in any publication supported by this NOFO.
• Upon completion or termination of the HPAP-T1D project, the awardee is responsible for making all HPAP-T1D resources broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research, as appropriate. 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.
• The data management and sharing plan should include a sustainability strategy to ensure access to HPAP-T1D data by the community once the project period expires. 

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

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 How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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. 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 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 How to Apply – 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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - 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 NOFO 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 How to Apply - 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 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH.  Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.

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.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness bycomponents of participating organizations, 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

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.

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 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. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding. 

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.

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 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.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.

HHS recognizes that NIH 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.

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 System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. An applicant can review and comment on any information in the responsibility/qualification records available in SAM.gov. NIH will consider any comments by the applicant, in addition to the information available in the responsibility/qualification records in SAM.gov, 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 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.

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. 

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 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, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the 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:

• Recipient(s) 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 Program Director/Principal Investigator (PD/PI) 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 Notice of Funding Opportunity Announcement (NOFO) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• Recipient(s) 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 DHHS, PHS, and NIH policies.
• Recipients are responsible for their staff in maintaining confidentiality of the information as developed by the network/consortium, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the Steering Committee (SC) as well as any confidential information received by third party collaborators.
• Recipients must analyze, publish and/or publicly release and disseminate results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and achieving the goals of the NOFO.
• Data Management and Sharing Plan: 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. By the end of the funding or proprietary period, a recipient or study group may not continue to use or share study generated resources until those resources are available to the public via a NIDDK approved repository per the NIDDK approved plan. 
• Recipient(s) will be required to participate in a cooperative and interactive manner with members of the network/consortium including designated NIH staff (e.g., Program Official, Project Scientist, Project Coordinator).
• Recipient(s) agree to establish agreements amongst themselves that address the following issues: (1) procedures for data sharing among network/consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the network/consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing bio-specimens under an overarching Material Transfer Agreement (MTA) amongst network/consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• 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, applicable network/consortium policies, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network/consortium studies between recipient  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/consortium policies. Further, at the request of the NIDDK Program staff, any other network/consortium-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/consortium activities that includes access to any network/consortium generated resources (i.e., data and biosamples), or study results that are not publicly available, or using the name of the network/consortium or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.
• Recipients must agree to comply with the processes and goals as delineated within the NOFO. 
• Recipients must share data, materials, models, methods, information and unique research resources that are generated by the projects in concordance with Network/Consortium policies in order to facilitate progress. When appropriate, and in accordance with NIH policies, as well as NIDDK policies, Recipients will be expected to collaborate; share novel reagents, biomaterials, methods and models and resources; and share both positive and negative results that would help guide the research activities of other members.
• Upon completion or termination of the research project(s), the recipients are responsible for making all study materials and procedures broadly available (e.g., putting them into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making all study materials and procedures available to the scientific community and the NIH for the conduct of research. The Data Management and Sharing Plan should include a plan to accomplish the aforementioned things at the end of the study.
• Recipients may be asked to scientifically review applications for special opportunity pool funds, as it is deemed appropriate.
• Recipients will submit a list of milestones to the NIDDK. After the award, an initial face-to-face meeting between the Project Scientist, other relevant NIDDK/NIH staff, and the recipients will be scheduled. This meeting will have the main purpose of jump- starting the project and evaluating and modifying as necessary the proposed milestones.

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 Official and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award (NoA).The NIDDK Project Scientist(s), Project Coordinator, and Program Official may review and approve applications of the Special Opportunity Funds to ensure that they are within the scope of network/consortium research as described in the NOFO and NIH guidelines. 

An NIDDK Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows: 

1. Serve as the contact point for all facets of the scientific interaction with the recipient(s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the recipient on specific scientific and/or analytic issues.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.

3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.

4. Have substantial involvement assisting in the design and coordination of research activities for Recipients as elaborated below:

a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.

b. The NIDDK Project Scientist or Project Coordinator may coordinate activities among recipients by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results. 

c. Reviewing procedures for assessing data quality and study performance monitoring.

d. The NIDDK Project Scientist or Project Coordinator may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to 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. 

The NIDDK Program Official identified in the Notice of Award will:

1. Interact with the Program Director(s)/Principal Investigator(s) on a regular basis to monitor study progress. Monitoring may include regular communications with the Program Director/Principal Investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.
2. Review and approve protocols prior to implementation to ensure they are within the scope of peer review, for safety considerations, as required by federal regulations.
3. The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) participant safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.
4. Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
5. Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high-risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Areas of Joint Responsibility include:

In addition to the interactions defined above, NIDDK Project Scientist or Project Coordinator and Recipients shall share responsibility for the following activities:

Steering Committee (SC)

A Steering Committee organized by the HIRN will be the main governing body of the study.

The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among recipients, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results.  Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official and will provide periodic supplementary reports upon request.

The Steering committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating/statistical centers, if any) and co-investigator(s) as deemed necessary, and the NIDDK Project Scientist.  The final structure of the Steering Committee and voting procedures will be established at the first meeting.  The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees.  The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.  The NIDDK Program Official may serve as a non-voting member on the SC.

A Chairperson of the Steering Committee will be selected and voted on by the Steering Committee members. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings and by interacting closely with the recipients during protocol development and implementation. The NIDDK Project Scientist may not serve as Chairperson. The NIDDK program official will review the Committee’s selection for potential bias, conflicts of interest, or lack of required expertise. If the Program Official has concerns regarding selection of the Chairperson which are not satisfactorily resolved, the Program Official may withhold concurrence if approved by the Director, Division of Extramural Activities, NIDDK based on written justification.  In cases where Program Official concurrence is withheld, the Steering Committee will be required to make another selection. 

External Consultants 

An independent panel of External Consultants may be established by the HIRN Steering Committee, and meet at least once a year.  The HPAP-T1D External Consultants will periodically review interim progress and give feedback to the HIRN Steering Committee on adjustments and future directions. Members of the panel of External Consultants may be asked, on an ad hoc basis, to participate in the peer review of applications for new research initiatives that utilize special “opportunity pool” funds. The NIDDK Program Official will review the Committee’s selections for potential bias, conflicts of interest, or lack of required expertise. If the NIDDK Program Official has concerns regarding selection of one or more External Consultants which are not satisfactorily resolved, the NIDDK Program Official may withhold concurrence if approved by the Director of NIDDK Division of Extramural Activities based on written justification.  In cases where NIDDK Program Official concurrence is withheld, the Steering Committee will be required to make another selection.

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: A designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 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.

4. 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 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 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), 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 2 CFR Part 200.113 and Appendix XII to 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 (Responsibility/Qualification in SAM.gov, formerly 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 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Rajatava Basu, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 240-255-0845
Email: raj.basu@nih.gov

Ann A. Jerkins, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2242
Email: Ann.Jerkins@nih.gov

Craig Bagdon
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
Email: bagdonc@niddk.nih.gov

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 2 CFR Part 200.

This NOFO is supported under the authority of P.L. 118-42, Consolidated Appropriations Act, 2024; Division G, Section 102. “Extension of Special Diabetes Programs”.