Part 1. Overview Information

Key Dates

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

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background
Type 1 Diabetes (T1D) is a progressive immune-mediated disease that is preceded by an asymptomatic period of highly variable duration in humans. In addition to genetic susceptibility, it is believed that biological or environmental triggers contribute to the development of an autoimmune response targeting specifically and exclusively insulin-producing beta cells, and to the progressive disappearance of functional beta cells from the pancreatic islet, leading to the initiation and development of clinical T1D. Current immunomodulatory interventions result, at best, in the partial stabilization of beta cell function but do not lead to full recovery of endogenous insulin secretion. It is therefore important to focus future research efforts on the identification of the cellular and molecular events that contribute to or even drive the disease initiation in the human pancreas during the asymptomatic phase to facilitate the development of preventative or therapeutic interventions that could be administered at the earliest possible stage of the disease.

Critical to the development of these alternative therapeutic strategies is the characterization of specific cellular processes that may be dysregulated in or around beta cells in individuals at risk of developing T1D, and that may contribute significantly to early pathogenesis. Potential defects may include dysregulations in pathways controlling the processing of islet products (proteins, DNAs, RNAs, lipids, metabolites), the ability of beta cells to deal with metabolic overload; the homeostasis or signaling between the islet and other pancreatic or peri-pancreatic tissue compartments and cell populations; or the efficient clearing of damaged or senescent beta cells.

Also critical to the development of preventative and early-stage therapeutic strategies is the identification of cellular or molecular biomarkers of early disease that can report on alterations in islet health or changes in the interactions between immune cells and the islet compartment. The minuscule amount of pancreatic islet tissue makes it extremely difficult to detect beta cell-specific signals of stress or inflammation in peripheral blood. In that context, strategies that link biomarker discovery to a specific aspect of early pathogenesis are more likely to succeed than the simple and unguided exploration of differentially expressed signals in peripheral blood.

Research Goals and Objective
This initiative supports the exploration of the human cells and tissues for the discovery of specific cellular dysfunctions and changes in the islet environment that contribute to the disappearance of pancreatic beta cells in patients with T1D, the discovery of early biomarkers of human T1D pathogenesis, and the identification of therapeutic targets for the development of preventative or early treatment strategies. The use of genome-wide linkage analysis data can also be used in the context of this initiative to help gain a deeper understanding of the pathways that impact beta cell function and survival in T1D pathophysiology. Also of interest is the exploration of adaptive or defensive mechanisms employed by human beta cells to survive in an increasingly hostile disease environment, that could be exploited for the development of protective or regenerative therapeutic strategies.

Research goals responsive to this initiative include, but are not limited to:

• Identify events of cell dysfunction, stress, injury, plasticity or trafficking that take place in the human islet or its vicinity during the asymptomatic phase of T1D and may contribute to islet inflammation or beta cell immunogenicity, to include the roles played by the acinar, ductal, neuronal, vascular, interstitial, lymphatic or intestinal compartments in early disease processes;
• Identify the target genes of T1D risk variants that may directly modulate beta cell stress and survival phenotypes, and can provide novel insight into the intrinsic role of beta cells in T1D pathophysiology;
• Describe the contribution of impaired signaling (including ER stress, senescence, apoptosis, DNA repair) or processing pathways (including RNA splicing, RNA editing, posttranslational modifications of proteins) to islet inflammation or the generation of neoantigens; develop molecular tools to control these processes and pathways to study their contribution to disease initiation, or as a first step towards the development of early disease therapeutics
• Identify modified or misprocessed cell products that are specific of a stressed islet niche in early T1D (such as abnormal protein, RNA, or DNA species), may contribute to the development of a pro-inflammatory environment, and could be used as biomarkers of disease initiation;
• Identify cell products that are released in the circulation throughout the life of beta cells or in situations of stress (such as extracellular vesicles) and can be used to monitor beta cell health and disease initiation in at-risk individuals;
• Perform deep molecular profiling experiments to identify rare immune cell subtypes that are present in the pancreatic compartment and related lymphoid tissues during the asymptomatic phase of T1D, and demonstrate their contribution to T1D pathogenesis; demonstrate the potential of such immune cell subtypes as cellular biomarker of disease initiation; target these cells in a specific manner to prevent progression towards an autoimmune response;
• Perform deep epigenetic profiling (DNA and RNA modifications, chromatin marks, etc.) of T1D-relevant human cell types (islet cells, immune cells, etc.) to assess the impact of early disease environment on transcriptional regulations and cell function; explore whether altered epigenetic marks in specific cell subtypes can be used as indicators of beta cell or lymphocyte health and disease.
• Identify adaptive changes in human beta cells exposed to immune assault and inflammatory mediators that may affect their immunogenicity and susceptibility to killing, and the signaling pathways driving these protective responses; develop therapeutic or regenerative strategies based on the controlled manipulation of these pathways.
• Validate new biomarkers (including composite biomarker panels) and diagnostic tools in human clinical samples, and further develop detection assays for clinical applications through improvement in precision, throughput, reproducibility, scalability, and cost.
• Identify therapeutic targets in pathways that contribute to disease initiation (including but not limited to RNA or protein processing, DNA repair, early senescence, ER stress, inflammation) and develop new classes of therapeutic molecules for preventative or early treatment strategies in at-risk individuals.

Important differences in islet tissue environment (genetic, developmental, morphological, cellular and molecular) and in disease pathogenesis exist between humans and rodents. In the context of this RFA, human pancreatic tissues, live pancreatic tissue slices, isolated pancreatic islets, human IPSC-derived biomimetics and/or clinical samples should be used as primary experimental systems for the acquisition of new knowledge. In situations where the exploration of T1D pathogenesis, biomarker discovery or drug-testing can be significantly facilitated by the use of rodent models, limited use of such models is allowed if properly justified. In such situations, it is expected that results and hypotheses derived from the use of non-human models will be validated using human tissues or clinical samples in a systematic fashion and throughout the funding period of the grant.

In choosing a source of human tissues, applicants are encouraged to use high-quality repositories, biobanks and procurement networks, whether linked to NIDDK-funded clinical studies such as 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 (https://t1dexchange.org/). If available, pancreata that are either densely genotyped (such as from the NIH-supported GTEx collection: https://commonfund.nih.gov/GTEx or originating from donors with well-documented disease history or health records, should be used. If the project involves studying signaling or processing pathways that are dysregulated in stressed beta cells during the asymptomatic phase of T1D, biobanked samples collected through clinical studies that are unrelated to T1D could also be useful, such as biosamples generated by the TODAY study that focuses on T2D in adolescents (https://repository.niddk.nih.gov/studies/today/?query=TODAY ), or by any other clinical studies related to metabolic dysregulations with clinical samples accessible through the NIDDK Central Repository (https://repository.niddk.nih.gov/home/).

The assembly of multidisciplinary teams under a single application to help address the scientific challenges outlined in this initiative is encouraged (but not required), particularly to help combine complementary expertise (such as beta cell biology, immunology, experience with state-of-the-art omics technologies or analytical tools, surgical experience and access to human cadaver donors). Single-investigator applications from individuals with the required expertise to make a major contribution are also welcome.
The HIRN is dedicated to fostering the next generation of diabetes and islet biology investigators; Early Stage Investigators (ESIs) are therefore strongly encouraged to contribute and lead projects in response to this initiative, and to apply as Contact Principal Investigator.

Cooperative Relationships and Data Sharing

Upon funding, successful applicants will join 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. Specifically, successful applicants will join one of HIRN’s five consortia, CBDS, whose mission is to better define and detect the mechanisms of beta cell stress and destruction central to the development of T1D in humans, with the long-term goal of protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and preventing the progression to autoimmunity (https://hirnetwork.org/consortium/cbds ).

Regardless of the team-structure proposed in the U01 application, all CBDS investigators will be expected to work closely and collaboratively with their CBDS 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 CBDS investigators are expected to be made available to the research community. Because the individual U01 projects will be coordinated through CBDS, the timeline and processes for sharing within CBDS and with the community at large will be established by the CBDS NIDDK Project Scientist or the CBDS Steering Committee. All participants will be expected to adhere to these policies as a term of the award. Policy documents for CBDS will be accessible on the HIRN website.

As a consortium, CBDS 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 CBDS activities. At a minimum, data and analytical tools generated by CBDS investigators should become easily accessible through the HIRN portal. All CBDS participants 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. The NIDDK staff will designate a CBDS investigator to represent CBDS on the HIRN Trans-Network Committee (HIRN-TNC) who will be expected to participate to all meetings of the HIRN-TNC. CBDS Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must participate in person to the annual HIRN Investigator Scientific Meeting, as well as in CBDS Steering Committee teleconferences to be held at least bi-annually. All participants will be obligated to abide by the policies adopted by the majority vote of the CBDS Steering Committee. In the application, research project budget requests must include costs for the PD/PI and up to three other members of the individual project to attend the annual HIRN Investigator Scientific Meeting. The annual HIRN Investigator Scientific Meeting will last 2-3 days In addition to the annual meeting of the HIRN, monthly CBDS webinars will be organized to facilitate early exchange of scientific results between CBDS investigators and to update CBDS investigators on HIRN-related activities. All CBDS teleconferences will be organized and administered by the HIREC. Note that the HIREC will support costs of all CBDS and HIRN-related meetings except for costs for research project investigators to travel and attend the meetings. The HIREC is also responsible for providing and maintaining a record of minutes of all CBDS meetings, which will be approved by the CBDS Steering Committee.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

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)
• 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

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

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

Research Strategy:

The applicant must:

• Provide a detailed description of the rationale for the proposed research strategy, based on preliminary data and current understanding of the potential contribution of the biological mechanism to be investigated to human T1D pathogenesis;
• Describe the potential of the proposed research for a greater understanding of human T1D pathogenesis, or for the detection, monitoring and/or treatment of the disease. The project should be focused on increasing our understanding of human disease biology (as opposed to mouse or other animal models), or at developing knowledge, tools and approaches that could lead to significant translational outcomes in the future;
• Describe how the project could benefit from interactions and collaborations with CBDS and HIRN colleagues.

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

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Applicants should describe how they plan to share data and reagents with their CBDS and HIRN colleagues, as well as with the larger scientific community.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. When involving human subjects research, clinical research, and/or NIH-definedclinical 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.

All instructions in the SF424 (R&R) Application Guide must be followed. Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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 Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. 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 components of participating organizations, 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.

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

Section V. Application Review Information

1. Criteria

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed). Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

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

Specific to this FOA: Will the project contribute significantly to the overall mission of the CBDS by uncovering specific cellular dysfunctions and changes in the islet environment that contribute to the disappearance of pancreatic beta cells in patients with T1D, or discovering early biomarkers of human T1D pathogenesis, or identifying novel therapeutic targets for the development of preventative or early treatment strategies?

Investigator(s)

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

Specific to this FOA: How will the investigator(s) benefit from interactions and collaborations with their CBDS and HIRN colleagues? How do such interactions contribute to the overall scientific mission of CBDS and HIRN?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

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

Specific to this FOA: Is the project clearly focused on increasing our understanding of human disease biology (as opposed to mouse or other animal models), or at developing knowledge, tools and approaches that could lead to significant translational outcomes in the future? Are planned interactions with the applicant’s CBDS and HIRN colleagues adequately described?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not applicable

Renewals

Not applicable

Revisions

Not applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

Specific to this FOA: Is the plan for data sharing with HIRN and the scientific community satisfactory?

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA. Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council . 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 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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee 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 awardee 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: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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.htmlor call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, and other HHS PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement U01, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

Primary responsibilities of the PD/PI:

• CBDS Awardee(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 CBDS Principal Investigator/Program Director will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• The CBDS Awardee will retain custody of and have primary rights to the data and software developed under these awards until time of release to his/her HIRN colleagues and to the general public as required by current policies regarding rights of access as developed and published by HHS, PHS, NIH/NIDDK and the HIRN.
• All staff of the CBDS Awardee 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.
• CBDS awardees must analyze, publish and/or publicly release and disseminate results, data, metadata 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 goals of the FOA.
• All staff of the CBDS Awardee will be required 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 CBDS.
• CBDS awardees are expected to share with their HIRN colleagues all data, materials, models, methods, information and unique research resources that are generated by the projects in accordance with HIRN and CBDS policies in order to facilitate progress towards achieving HIRN's mission and goals. When appropriate, and in accordance with NIH policies, awardees 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 HIRN members.
• CBDS awardees will submit a list of milestones and project deliverables to the HIREC prior to the initial HIRN meeting, and will update this list annually.
• CBDS Awardees agree to establish agreements amongst themselves that address the following issues: (1) Procedures for data sharing among consortium members and data sharing with any third party (including both industry and academic partners), as appropriate and consistent with achieving the goals of the program; (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 biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner; and (5) Procedures for reviewing publications, determining authorship, and industry access to publications. The NIDDK Program Official may consult with others at NIH including the NIDDK Technology Advancement Office regarding these agreements and issues.

  Any involvement of a third-party (including industry, academia, and foundations) in the study and network activities that includes access to any network study 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. Maintaining confidentiality of information: The awardee(s) will maintain the confidentiality of the information developed by the investigators (i.e., protocols, data analysis, conclusions, etc.) as well as proprietary information of an individual company or other entity collaborating with the study. Any exception requires written approval from NIDDK Program staff.

• Any third-party (including industry, academia, and foundations) collaboration 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.

• CBDS awardees must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
• Upon completion or termination of the research project(s), the CBDS awardees 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 sharing plan should include a plan to accomplish this at the end of the study.
• CBDS awardee(s) agree to the governance of the study through a Steering Committee: The PD/PI, or contact PD/PI in the case of multi-PD/PI awards, will serve as a voting member of the Steering Committee and will attend all meetings of the Steering Committee. Each full member will have one vote. The awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees.
• CBDS awardees must serve on CBDS subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator's Retreat.
• CBDS awardees may be asked by NIH staff to scientifically review applications for special opportunity pool funds, as deemed appropriate.

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

• The NIDDK will designate program staff, including a Program Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.
• The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or CBDS policy and procedure, (2) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or (3) concerns related to human subject safety that prompt the need for premature termination.
• The NIH will invite experts with relevant scientific expertise to provide feedback to the NIH on CBDS activities. The External Experts will meet to review the progress of the research projects and to advise NIH staff of scientific developments and opportunities that may enhance the achievement of the study goals.

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

• The NIH Project Scientist will have substantial scientific programmatic involvement in research coordination and performance monitoring. The dominant role and primary responsibility for these activities resides with the awardee, however, specific tasks and activities in carrying out the studies will be shared among the awardees and the NIH Project Scientist.
• The NIH Project Scientist will coordinate and facilitate the research projects, attend and participate in all meetings of the CBDS, and act as a liaison between the Awardee and the External Experts.
• The NIH Project Scientist(s) will be a member(s) of the Steering Committee and, as determined by that committee, and its Subcommittees as needed. Only one NIH Project Scientist will vote on the Steering Committee. Other designated NIH program staff attending the steering committee meetings will be an ex officio (non-voting) member(s).
• The NIH Project Scientist, and other designated NIH program staff will help the Steering Committee develop and draft operating policies.
• The NIH Project Scientist and Program Officer will review the scientific progress, cooperation in carrying out research, and maintenance of high quality research in each of the individual research project, and review the project for compliance with operating policies developed by the CBDS. Based on this review, the Project Scientist in conjunction with the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of scientific progress or failure to adhere to policies established by the CBDS. Review of progress may include regular communications between the Principal Investigator/Program Director and NIH staff, periodic site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
• The NIH Program Scientist and Program Officer will review applications for Special Opportunity Funds for responsiveness to program goals to ensure that they are within the scope of CBDS research as described in the Funding Opportunity Announcement and NIH guidelines. The NIH will enlist additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist in carrying out the goals and aims of the approved studies. The NIH will have one vote for any key committees, regardless of the number of NIH consultants involved in the project.
• The NIH Project Scientist serves as a resource with respect to other ongoing NIH activities that may be relevant to CBDS studies to facilitate compatibility and avoid unnecessary duplication of effort.
• The NIH Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data and in the publication of results.
• The NIH Project Scientist may review procedures for assessing data quality and monitor study performance.
• The NIH Project Scientist may be a co-author on study publications. In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

Areas of Joint Responsibility::

• Through the CBDS Awardee(s) and NIH staff, CBDS will cooperatively develop and implement processes to submit information and data to the HIREC, 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 Funding Opportunity Announcement.
• There will be an initial face-to-face meeting of HIRN and a minimum of 2 CBDS meetings (teleconferences or face-to face meetings) annually. CBDS awardees, the CBDS Project Scientist, and the CBDS Program Official are expected to attend these meetings. One of these bi-annual meetings could be combined with the annual HIRN Investigator Scientific Retreat.

CBDS Steering Committee

• CBDS awardees agree to the governance of the CBDS through a Steering Committee:
• On an annual basis, and following input from the CBDS Steering Committee members, NIDDK staff will appoint a Steering Committee Chair who will be in charge of facilitating the CBDS Steering Committee meetings and teleconferences. In collaboration with the HIREC and the NIH Project Scientist, the Chairperson is responsible for coordinating the Steering Committee activities, for preparing meeting agendas and for chairing meetings.
• The Steering Committee, including the Project Scientist, is responsible for establishing and implementing processes and criteria for recommending special projects for consideration for special opportunity funds by NIH staff.
• The NIH Project Scientist may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees.
• The Steering Committee will be composed of the Principal Investigators/Program Directors for each U01, or by U01 representatives (one per U01 grant) chosen by the Principal Investigators/Program Directors in the cases of multi-PI grants, and the NIH Project Scientist. Only the U01 PI/PD or multi-PI U01 representatives and the NIH Project Scientist will be voting members of the Steering Committee and will attend all meetings of the Steering Committee. Each full member will have one vote. Other designated NIH program staff attending the steering committee meetings will be ex officio (non-voting) members. The CBDS Steering Committee will meet at least twice a year.
• All major scientific and policy decisions will be determined by voting policies as established by the Steering Committee at the initial meeting. This committee will operate to develop collaborative protocols, identify impediments to success and strategies to overcome them, develop shared tools for disseminating information about the projects, and identify opportunities for sharing techniques, materials, information and tools developed within each individual project. Steering Committee activities and decisions will consider the advice of the External Experts.
• The NIH Project Scientist will help the Steering Committee develop and draft operating policies.
• NIDDK staff, in concert with the Steering Committee, will have the option to redirect research activities being pursued within the U01 grants if it is considered beneficial to the overall program.
• The Awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees. Awardees must serve on CBDS subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator’s Retreat.

HIRN Trans-Network Committee (HIRN-TNC)

• The HIRN-TNC will consist of: the PD/PI of the HIREC and the Steering Committee Chairs and Project Scientists of the HIRN scientific topic consortia (CHIB, CBDS, CMAI, CTAR and HPAC); 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 organizing the yearly HIRN Scientific Investigator’s Retreat.
• The TNC will meet by teleconference at least twice a year and will be organized by the HIREC. Meetings will be used to discuss and 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 CBDS members through in-person, electronic, or teleconference meetings, as appropriate. The HIREC is responsible for providing and maintaining a record of minutes of all EC meetings, which will be approved by the EC.

Expert Scientific Panel (ESP)
An independent panel of 2-3 External Experts will be appointed by the NIDDK and meet by teleconference with the CBDS Project Scientist and the CBDS Project Officer at least once a year. The CBDS-ESP will be updated on progress and give feedback to NIH on adjustments and future directions for the CBDS research projects. On an annual basis, and following input from the ESP members, NIDDK staff will appoint an ESP Chair who will be required to attend the annual HIRN Investigator Scientific Retreat, to participate to the CBDS Steering Committee meetings as ex-officio, and to serve as the CBDS-ESP representative to the larger HIRN-ESP that will also meet once a year. The CBDS ESP Chair will be tasked with relaying the CBDS Steering Committee recommendations for new Opportunity Funds Initiatives to the HIRN-ESP. All CBDS-ESP members will also be invited to listen as ex-officio to CBDS Steering Committee meetings. Members of the CBDS-ESP may be asked, on an ad hoc basis, in the peer review of applications for new research applications that request "opportunity pool" funds. The HIREC will support costs for teleconferences between the ESP and the CBDS Steering Committee, will arrange the CBDS-ESP and HIRN-ESP teleconferences, maintain a record of minutes, and support costs for the CBDS-ESP chair to participate in the annual HIRN Investigator Scientific Retreat.

Dispute Resolution

Disagreements that may arise in scientific/technical matter or programmatic matters (within the scope of the award) between award recipients and the NIDDK may be brought to arbitration after first attempting to resolve the issue through the Steering Committee or its subcommittees, as appropriate. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

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

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 Award Term and Conditions 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 threatensubmission by the due date, and post-submission issues)

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Olivier Blondel, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-7334
Email:[email protected]

Najma Begum, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8894
Email: [email protected]

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

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

This FOA is supported under the authority of P.L. 116-94, Further Consolidated Appropriations Act, 2020; Section 402. Diabetes Programs.