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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) solicits applications to participate in a new consortium being added to the Human Islet Research Network (www.hirnetwork.org) - the Consortium on Modeling Autoimmune Diabetes (HIRN-CMAD). The goal of the HIRN-CMAD consortium will be designed to develop and optimize in vitro and in vivo disease models that enable the study of human islet and immune interactions in type 1 diabetes (T1D).

HIRN-CMAD awards will use the UG3/UH3 cooperative agreement funding mechanism. The UG3 phase is designed to allow exploratory studies to establish the initial concept of such model systems, with milestones focused around replicating key aspects of human T1D pathophysiology. The subsequent UH3 phase will be expected to refine and validate the utility of the models for mechanistic studies of islet-immune interactions and for testing new and novel therapies. A UG3 project that meets its milestones will be administratively considered by the NIDDK for transition to the UH3 award. Applicants responding to this NOFO must address objectives for both the UG3 and UH3 phases.

Background

In 2014, NIDDK established the Human Islet Research Network (HIRN) to organize and support collaborative research focused on the loss of functional beta cell mass in T1D. HIRN’s 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 people with diabetes. The HIRN program is configured as a modular network of small research consortia, each defined by a specific set of research priorities. The network structure helps facilitate interactions between small communities of investigators organized around common biological and/or technological challenges, with the overall goal of developing innovative strategies for the treatment, prevention, and monitoring of T1D.

The HIRN-Consortium on Modeling Autoimmune Interactions (HIRN-CMAI) and the Consortium on Human Islet Biomimetics (CHIB) are two of the four founding HIRN consortia. HIRN-CMAI investigators have been working to develop innovative in vivo models of human T1D immunobiology that can be used by the research community to measure the molecular and cellular events that lead to loss of human beta cell function in T1D and for testing of innovative therapies. HIRN-CHIB investigators have focused on designing and building micro-physiological system (MPS) platforms that support the survival, maintenance, and function of human islets for prolonged periods of time. These also incorporated immune components to mimic aspects of the autoimmune response and approaches for immune modulation in vitro. HIRN-CMAI investigators have made tremendous strides toward establishing mice with humanized immune components that allowed the exploration of human innate and adaptive immunity in T1D and identification of thymic selection defects that may lead to disease. Progress has also been made in cataloguing and cloning islet-infiltrating T cells and developing regulatory T cells with chimeric antigen receptors to target and protect human islets. HIRN-CHIB investigators have developed in vitro devices that enabled durable human islet culture with measurement of hormone release, in situ imaging, and real-time functional assessment through biosensors. Some MPS devices allowed interactions between vascularized islet and immune cells and demonstrated T cell migration, extravasation, and beta cell killing. Moreover, there has been great progress within and outside both consortia in differentiating iPSC lines toward pancreatic islet, immune, and mesenchymal lineages that pave the way toward establishing fully isogenic human systems to study T1D using in vitro and in vivo model systems.

HIRN-CMAD is designed to promote collaboration among scientists involved in both humanized mouse and human organ-on-a-chip efforts to advance T1D research along the translational pipeline. Projects involving bioengineers, cell biologists, immunologists, and endocrinologists are expected to lead to unique synergies that will optimize preclinical developments and translational research in T1D. It is anticipated that the development of these new/advanced models will contribute to a better understanding of the etiology/pathogenesis of T1D, uncover mechanisms underlying diabetes heterogeneity, and lead to improved evaluation of targeted therapies.

Research Opportunities and Scope

HIRN-CMAD is expected to build upon existing technologies and advances made using in vitro and in vivo modeling strategies to create combined, multi-faceted, multi-component systems that will support mechanistic interrogation of T1D pathogenesis/pathophysiology. While no one model will be a perfect representation of human disease, each in vivo and in vitro model system should be designed to address a key feature of human T1D. Each model comes with certain experimental limitations and unique capabilities to probe the dynamics of islet and immune cell changes during disease progression. These platforms should be further adapted to identify or test therapies designed to prevent, delay, or reverse steps in T1D pathogenesis. T1D models are particularly needed to study early islet dysfunction, autoimmunity initiation, and/or other metabolic perturbations present during the early stages of disease for which there are still few clinical interventions. Applicants are strongly encouraged to include both in vivo and in vitro models in their research plan as powerful complementary approaches to interrogate T1D biology.

Studies that are of interest could include the following but are not limited to:

• Fully isogenic modeling of islet cells and immune cells: Current models mostly rely on experienced human immune cells recovered from patients to study T1D autoimmunity. Of particular interest are studies that employ isogenic immune, stromal, and islet components generated from common iPSC lines to establish platforms to study T1D-related changes in lymphocyte development and the expansion of pathogenic populations. Technologies are also needed to monitor changes in immune population dynamics in response to changes in islet cells, such as how upregulation of islet neoantigens and the adoption of the senescence-associated secretory phenotypes may trigger immune activation.
• Modeling the islet niche: Incorporation of multiple cell types within the islet niche with proper spatial organization may ultimately be required to recapitulate islet physiology under both normal and pathological conditions. For example, models that include elements of the nervous system, as well as fully formed intra-islet vasculature including endothelial cells and pericytes, may be necessary to move the field forward. Other aspects of islet niche organization and function that remain to be tested in these advanced, multi-component model systems include the role of ECM components and exogenous soluble factors, including circulating hormones and cytokines, in the maintenance, growth, and/or destruction of human islets in T1D.
• Changes in islet function and behavior: Current stem cell derived islet-like cells still do not reproduce many key features of primary islet physiology. The ability to reproducibly generate islets with all representative endocrine cell types in appropriate ratios and spatial arrangements remains a challenge for the field. Improvements in cell composition, identity, and structure are needed to recreate an islet mini organ more accurately resembling an endogenous islet. Mechanistic insights into alpha cell and beta cell dysfunction and changes in islet cell identity, function, or behaviors (gene expression, antigen presentation, etc.) that occur early in the disease process may be gained in these systems that will have implications for initiating pathogenic islet-immune interactions. Novel tools, reagents, and technologies are also needed to enable detection and monitoring of changes in islet cell identity and function, especially in the context of immune responses and other environmental cues such as metabolic stress, viral infection, etc.
• Recapitulating autoimmune pathogenesis:
  • Developing platforms needed to interrogate T1D-relevant changes in lymphocyte development, expanding the types of immune cells that develop or that may be assayed in the in vitro or in vivo systems (including B cells and plasma cells), and devising/deploying new technologies as needed to monitor changes in immune cell population dynamics as they respond to changes in islet structure and function over time in both in vitro and in vivo models.
  • Mechanistic dissection of human thymocyte development and function in the context of T1D, and to enable studies exploring the role of the pancreatic lymph node or gut mucosal immune cells in T1D development.
• Identification of therapeutic targets and testing: Progress on optimizing these models should enable the identification of new therapeutic targets capable of modulating islet dysfunction and/or autoimmunity. Such studies should also be used to verify their utility for preclinical efficacy and safety testing. Specific in vivo models could be designed to test immunotherapies directed at certain immune effectors, regulators, and tolerance, as well as to assess engineered islet replacement therapies that are designed to evade allogeneic and autoimmune responses. Similarly, in vitro models could be adapted to provide pre-clinical assessments on a chip that may eventually replace existing models used for therapeutics testing.

UG3 and UH3 Phase Objectives

This funding opportunity uses a UG3/UH3 (Exploratory/Developmental Phased Award Cooperative Agreement) Phased Innovation Award mechanism. The UG3 phase is intended to be the initial development period of these in vitro/in vivo models. The UG3 phase will support preparatory studies including activities such as readying the differentiation of iPSCs to all required cell components; designing and constructing novel tools and reagents; and successful assembly of the models.

The UH3 phase is focused on refining and validating the model designs to demonstrate translational utility. Each project proposal should describe an overall goal regarding which features of T1D clinical pathophysiology are meant to be replicated, and which translational aspects are to be tested by the end of the UH3 phase. While primary human cells and tissues may be used to establish and verify initial utility of the approach, the research plan should focus on incorporation of human iPSC-derived cells into the system as the ultimate goal.

For in vitro systems, the UG3 Phase should be used to develop multiplexed platform technology that enables durable and dynamic interactions between islet and immune cells involved in the T1D inflammatory/autoimmune processes, and its regulation within a 3D environment. For in vivo systems, the UG3 phase should begin by first defining which human cell components, tissue architecture, and functional competence need to be established within the in vivo environment. Applicants should clearly define the readouts and endpoints they wish to achieve with the proposed model(s) that will be necessary to enable the translational study later in the UH3 phase.

Examples of UG3 Phase Objectives (up to 2 years) include but are not limited to:

• Generation of human iPSC derived islet organoids from individuals with T1D and pre-T1D, or iPSC-derived organoids from non-diabetic individuals that have been engineered to contain T1D-associated genetic risk variants;
• Multiplexed device designs that enable controlled and targeted temporal and spatial introduction and removal of soluble factors and cellular components while allowing in situ real-time imaging of the 3D tissue;
• Incorporation of other supportive cells to establish vascularized islet tissue with intra-islet capillaries and/or innervation, lymphatic drainage, and lymph nodes in vitro and in vivo;
• Inclusion of human beta/alpha/other islet subtypes and immune populations involved in promoting islet inflammation and antigen-specific interactions in vitro and in vivo;
• Inclusion of a well-conceived plan to develop an in vitro and/or in vivo human iPSC-based system consisting of human beta, alpha, and other islet subtypes, CD8/CD4/DC/other relevant immune components, and supportive cells such as endothelial cells, mesenchyme, and neural components, etc. This plan should include a strategy to achieve maturation and glucose-responsiveness of human iPSC-derived beta and alpha cells;
• Incorporation of non- or minimally invasive assays for monitoring metabolic function such as reporter systems that will provide information in real-time to monitor beta cell function and health, as well as immune cell activation and effector/regulatory function;
• Developing and validating the tools needed to interrogate how islet dysfunction and/or destruction of human pancreatic beta cells is initiated;
• Determining human diabetes relevance of the models by preliminary testing of key experimental features and outcomes essential for proceeding to the UH3 phase of the study. Model establishment should demonstrate durability of human cell/tissue survival so that intended additional assays are feasible.

UH3 phase Objectives (up to 3 years) must include:

• Refining the model system to demonstrate stability and durability of the human cells/tissues.
• Demonstration of reproducibility of the models with iPSC lines from non-diabetic and T1D sources. Assembly of a fully isogenic human T1D model.

Additional examples of UH3 phase Objectives include but are not limited to:

• Cross-validation of T1D model endpoints with clinical measures in humans or physiologically relevant human tissues.
• Extensive characterization of clinical-pathological staging of the diabetes model with the corresponding stages of clinical disease using relevant biomarkers.
• Identification of therapeutic targets and conducting pre-clinical efficacy testing of candidate therapeutics to prevent, halt, or reverse T1D.

UG3/UH3 Milestones

All projects will be milestone-driven with clear go/no-go criteria that are quantifiable. Milestones with a timeline must be included in the application. Prior to funding an application, the Program Official will contact the applicant to discuss the proposed UG3 and UH3 milestones and any changes supported by NIH staff. The Program Official and the applicant will negotiate and agree on a final set of approved UG3 milestones which will be specified in the Notice of Award. These milestones will be the basis for judging the successful completion of the work proposed in the UG3 stage and progress toward interim milestones in the UH3 stage. Only UG3 projects that meet their milestones will have an opportunity to move to the UH3 phase. UH3 milestones will be the basis for judging progress towards and completion of interim milestones in the UH3 phase.

Composition of the applicant team

The assembly of multidisciplinary teams under a single application to help address the scientific challenges outlined in this initiative is encouraged, particularly to help combine complementary expertise (such as beta cell biology, immunology, stem cell biology, engineering, access to human cells, etc.).

Meetings of HIRN-CMAD

Program Directors/Principal Investigators of HIRN-CMAD must participate in an initial in-person meeting soon after awards are made, in the annual HIRN Investigator's Meeting, in CMAD teleconference meetings to be held at least tri-annually thereafter, and in the in-person HIRN-CMAD Scientific Retreat, to be held annually. All participants must be obligated to abide by the policies adopted by the majority vote of the HIRN-CMAD Steering Committee. In the application, research project budget requests should include costs for the PD/PI and up to two other members of the individual project to attend the annual HIRN Investigator's Meeting and the annual in-person HIRN-CMAD Scientific Retreat.

Additional Considerations

Cells: The use of transformed or immortalized cell lines is discouraged, except for preliminary, proof-of-concept studies. The use of primary cells and organ explants in initial studies progressing to iPSCs is encouraged. The current NIH guidance on stem cell usage can be found at http://stemcells.nih.gov/policy/pages/2009guidelines.aspx. In choosing a source of human cells and tissues, applicants are encouraged to use high-quality repositories, biobanks and procurement networks, whether linked to NIDDK-funded clinical studies such as the Integrated Islet Distribution Program (https://iidp.coh.org/), the Diabetes Prevention Trial-Type 1 (DPT-1) or the Type 1 Diabetes Trialnet (https://repository.niddk.nih.gov/home/, or supported by private research efforts such as the JDRF nPOD (https://www.jdrfnpod.org/) or the T1D Exchange (http://www.t1dexchange.org/). If available, pancreata that are either densely genotyped (such as from NIH-supported the GTEx collection: https://commonfund.nih.gov/GTEx) or originating from donors with well-documented disease history or health records, should be used.

Collaboration: Collaborative interactions are a critical aspect of this NOFO. The development of humanized mouse models and MPS for T1D will require extensive collaboration among immunologists, tissue engineers, stem cell biologists, diabetes experts, and clinicians. Further collaboration between funded award teams to compare, contrast, and improve in vitro and in vivo models within HIRN-CMAD will be highly encouraged.

Applications Not Responsive to this NOFO

Applications that include the following types of studies will be considered non-responsive and will not be reviewed:

• Development of 3D tissues specifically for transplantation as a therapeutic modality
• Engineering of non-human tissue models
• Development of simple cell mixtures and clusters in static incubation formats
• Development of systems for which an informative animal model already exists
• Clinical trials

Cooperative Relationships and Data Sharing

Successful applicants will establish and join the Consortium on Modeling Autoimmune Diabetes (CMAD). This consortium is expected to continue optimizing and translating in vitro and in vivo models that were developed within and outside HIRN-CMAI and HIRN-CHIB. Successful applicants will be expected to work collaboratively with all of their CMAD and HIRN colleagues and to contribute to an environment of sharing and trust across the network. All methods, reagents, resources, biomaterials, protocols, data, and models developed by CMAD investigators are expected to be made available to the research community, as appropriate and consistent with achieving the goals of the program. All participants will be expected to adhere to the sharing policies developed by the HIRN as a term of the award. All participants will be obligated to abide by the policies adopted the majority vote of the CMAD Steering Committee and the HIRN Trans-Network Committee (see "Cooperative Agreement Terms and Conditions of Award, Section VI.2.).

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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 NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, 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 Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

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

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Milestone Plan: The filename "Milestone Plan.pdf" should be used.

Milestones and timelines must be provided in the Milestone Plan document and will be evaluated as part of the scientific and technical merit of the UG3/UH3 application. Milestones and the timelines for each stage must be provided for each UG3 and UH3 section and include the following:

• Provide detailed quantitative criteria by which milestone achievement will be assessed.
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
• Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.

Applications that lack the Milestone Plan are considered incomplete and will not be peer reviewed.

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

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

Specific Aims: Provide the overall goals for hypotheses for the entire project period and identify separate Specific Aims to be accomplished in the UG3 phase and in the UH3 phase.

Research Strategy:

The applicant must:

• Include plans for collaboration among the scientific fields relevant to this NOFO, i.e., T1D disease expertise, immunology expertise, engineering expertise, stem cell biologists, etc.
• Provide separate sections that describe both the UG3 and UH3 phases
• Provide a description of the hypothesis to be tested in the UH3 phase of the study

Transition from the UG3 to the UH3 phase is contingent upon the successful completion of the transition milestones. The specific milestone(s) proposed in the application will depend on the goals of the application and the accomplishments necessary in the UG3 phase for advancement into the UH3 phase. Regarding Go/No-Go Transition Milestones for transition from the UG3 Phase to the UH3 Phase, the applicant must:

• Include clearly identified Go/No-Go transition milestones for completion of the UG3 phase at the end of Year 2 and transition to the UH3 phase for 3 years of additional funding.
• Provide a timeline (Gantt chart) including milestones for all studies. Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years.

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:

• 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.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan (DMS Plan). All applications, regardless of the amount of direct costs requested for any one year, must address a DMS 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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 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 the 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.

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.

Milestone Plan

How appropriate are the milestones provided for the UG3 and UH3 phases of the overall project? How appropriate are the quantitative criteria used to assess milestone achievement of the specific aims in the UG3 and UH3 phases of the project? How feasible is the overall timeline for the UG3 and UH3 phases? How appropriate are the critical decision points (i.e., go/no go decision points) within the UG3 and UH3 phases? How adequately has the applicant addressed the criteria in the UG3 phase to assess milestone completion in order to make a decision to advance studies to the UH3 phase?

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 NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

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

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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.

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.

2. Administrative and National Policy Requirements

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

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

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

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

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

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

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

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

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

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

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 (HHS) 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 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 (NOFO) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• Recipients(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 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 consortium including designated NIH staff (e.g., Program Official, Project Scientist).
• Recipient(s) agree to establish agreements among themselves that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners; (2) 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; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing bio-specimens under an overarching MTA among 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, 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, 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.
• Recipient(s) agree to participate in a cooperative and interactive manner with NIH staff, one another and with the Human Islet Research Enhancement Center (HIREC) in all aspects of CMAD.
• Recipient(s) agree to share data, materials, models, methods, information, and unique research resources that are generated by the projects in accordance with CMAD policies in order to facilitate progress. When appropriate, and in accordance with NIH policies, Recipient(s) 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 CMAD members.
• Recipient(s) agree to submit a list of milestones and project deliverables to the HIREC prior to the award activation and will update this list annually.
• Upon completion or termination of the research project(s), the Recipient(s) are responsible for making all study materials and procedures 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. The Data Management and Sharing Plan (DMS Plan) should include a plan to accomplish this at the end of the study.
• Recipients may be asked to scientifically review applications for special opportunity pool funds, as it is deemed appropriate.
• Ensuring all staff of the CMAD Recipients will maintain the confidentiality of the information developed by the investigations, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators.

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 stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award.

An NIH IC 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:
   1. 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.
   2. The NIDDK Project Scientist 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.
   3. Reviewing procedures for assessing data quality and study performance monitoring.
5. The NIDDK Project Scientist 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 will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Through the Recipient, Steering Committee and NIH staff, the study members will cooperatively develop and implement processes to submit information and data to the Coordinating Center (CC), determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the study, consistent with NIH policies and achieving the goals of the program as described in the NOFO.
• There will be an initial face-to-face meeting of HIRN and a minimum of 2 CMAD meetings (teleconferences or face-to face meetings) annually. CMAD Recipients, the CMAD Project Scientist, and the CMAD Program Official are expected to attend these meetings. One of these bi-annual meetings could be combined with the annual HIRN Investigator’s Meeting.

Steering Committee (SC)

A Steering Committee organized by the study investigator(s) 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 should be consulted regarding the selection of the Chairperson to provide any feedback regarding concerns regarding potential for bias or conflict of interest or lack of required expertise.

HIRN Trans-Network Committee (TNC)

• The HIRN-TNC will consist of: The Director(s) of the HIREC, NIDDK Project Scientists, and representative PIs chosen among the Recipients; the TNC is not a governing body and does not cast votes.
• The TNC will facilitate communication and foster collaboration across the different consortia.
• The TNC will be responsible for overseeing organization of the annual HIRN Investigators Meeting.
• The TNC will meet by teleconference at least twice a year and will be organized by the HIREC. Meetings will be used to discuss, prioritize, and review the progress of applications that will use "opportunity pool" funds. Subcommittees of HIRN, as well as working groups for scientific planning may be established and require participation by the CMAD members through in-person, electronic, or teleconference meetings, as appropriate. The HIREC is responsible for providing and maintaining a record of minutes of all TNC meetings, which will be approved by the TNC.

External Consultants

An independent panel of External Consultants may be established by the Steering Committee. The External Experts will review periodically interim progress of the UG3/UH3s and report to the Steering Committee members. Members of the panel of External Experts 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 Steering Committee may invite External Consultants with relevant scientific expertise for the sole purpose of consultative advice on scientific developments and opportunities that may enhance the achievement of the study goals.

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

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.

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 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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

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

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

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

Albert Hwa, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-1525
Email: [email protected]

Maggie Morris Fears, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5444
Email: [email protected]

Elena Sanovich, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8886
Email: [email protected]

Craig E. Bagdon, MPA
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
Email: [email protected]

Mark Hodor
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5712
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

This NOFO is supported under the authority of P.L. 118-15, Continuing Appropriations Act, 2024 and Other Extensions Act; Section 2322. Extension of Special Diabetes Programs .