Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

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

Funding Opportunity Title
Discovery of Early Type 1 Diabetes Disease Processes in the Human Pancreas [HIRN Consortium on Beta Cell Death and Survival (CBDS)] (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
Reissue of RFA-DK-19-024
Related Notices
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Notice of Funding Opportunity (NOFO) Number
RFA-DK-23-007
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.847
Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) requests applications to explore human pancreatic tissues and the immune compartment for the discovery of specific signaling or processing pathways that may contribute to the asymptomatic phase of T1D, the discovery of early biomarkers of T1D pathogenesis, the development of diagnostic tools for the detection and staging of early T1D in at-risk or recently-diagnosed individuals, and/or the identification and biological validation of therapeutic targets for the development of preventative or early treatment strategies. Successful applicants will join the Consortium on Beta Cell Death and Survival (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 of preventing the progression to autoimmunity. The CBDS is part of a collaborative research framework, the Human Islet Research Network (HIRN, https://hirnetwork.org/), whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This NOFOwill only support studies with a primary focus on increasing our understanding of human disease biology (as opposed to rodent or other animal models). This NOFOwill not accept applications proposing a clinical trial.

Key Dates

Posted Date
April 01, 2024
Open Date (Earliest Submission Date)
June 10, 2024
Letter of Intent Due Date(s)

November 6, 2023

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
July 09, 2024 July 09, 2024 Not Applicable November 2024 January 2025 April 2025

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).

Expiration Date
July 10, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background.

Type 1 Diabetes (T1D) is commonly described as 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 and/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 development of clinical T1D, as measured by the progressive detection in peripheral blood of pancreatic islet autoantibodies.

While most researchers in the field remain convinced that autoimmunity is the main driver of T1D in humans, recent developments suggest a greater contribution of beta cell injury to the loss of beta cell mass and to disease pathogenesis than previously acknowledged. A large longitudinal study in children with high genetic risk of developing T1D has reported a sharp rise in postprandial blood glucose two months before the detection of autoantibodies to beta cell antigens, suggesting that a severe beta cell insult precedes the development autoimmunity. Findings of shrinkage of the exocrine pancreas before T1D diagnosis suggest that processes involving the whole pancreatic tissue are at play in disease initiation. Further weakening the theory of a massive autoimmune destruction of beta cells, histology of the pancreas of patients with T1D shows, on average, mild insulitis affecting fewer than 10% of pancreatic islets, in stark contrast with the massive influx of reactive immune cells in all islets and throughout the pancreas observed in the NOD mouse, which is still considered the best animal model for human T1D. The very notion that disappearance of beta cells from the T1D islet results primarily from a massive destruction of this cell population is itself complicated by the observation that pancreata of patients with recent-onset T1D contain a significant number of “empty” or “ghost” beta cells that have lost their ability to secrete mature insulin. This suggests that cell plasticity contributes to insulin-positive cell depletion in T1D, raising the attractive possibility of manipulating this very plasticity for therapeutic purposes. Furthermore, on the clinical side, most therapeutic strategies of the past two decades aimed at preventing or treating T1D have focused on modulating the immune system, with only limited success and with at best a delay in disease progression. Finally, clinical manifestations are different according to age of onset, further suggesting that T1D is a heterogeneous disease in which specific factors or combinations of factors (autoimmunity, beta cell degeneration, metabolic stress, etc.) may be more important in subgroups of patients. 

Taken together, the observations listed above suggest that the etiology of beta cell death in T1D is likely multifactorial and may vary depending on subtypes. These observations should serve as catalysts to reevaluate the interplay of immune cells and beta cells during the asymptomatic phase and to better describe the cellular and molecular events that drive disease initiation in order to: a) facilitate the discovery of early biomarkers to better identify individuals entering the asymptomatic stage of the disease and what disease subtype they may belong to, and b) develop preventative or therapeutic interventions to be administered at the earliest possible stage, that may include synergistic drug combinations targeted at both the beta cells and the most relevant immune cell population.

Research Goals and Objective

This initiative supports the exploration of 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. 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 beta cell survival, islet inflammation or beta cell immunogenicity, to include the roles played by the immune, acinar, ductal, neuronal or vascular compartments in early disease processes;
  • Describe the contribution of impaired signaling (including ER stress, senescence, apoptosis and DNA repair) or processing pathways (including RNA processing, RNA editing, translation and posttranslational modifications of proteins) to islet inflammation or the generation of neoepitopes; develop molecular tools to study the contribution of these pathways to disease initiation;
  • Describe the role played by specific cell types within the broader islet environment in disease initiation and progression, including endocrine cells, exocrine cells, ductal cells, macrophages, vascular and peri-vascular cells, and neurons; explore how various cell types facilitate or protect against the autoimmune attack on beta cells, and how the cellular composition and architecture of the islet and peri islet environment contribute to the heterogeneity and lobularity of pancreatic pathology in human T1D;
  • Identify modified or misprocessed cell products that are specific of a stressed islet niche in early T1D (such as abnormal or uniquely edited protein, RNA, or DNA species), contribute to the development of a pro-inflammatory environment, and could be used as biomarkers of disease initiation;
  • Identify the set of conditions that make a beta cell (or a subset of beta cells) turn immunogenic; develop human cell-based models and experimental platforms to help answer this fundamental question;
  • Perform deep molecular profiling of the immune compartment to identify rare immune cell subtypes that may contribute to T1D pathogenesis or can be used as cellular sentinels to report on disease initiation and progression; discover multimodal immune signatures (e.g. surface proteins, transcriptional, and epigenetic) that can help identify disease initiation, stages of the disease and/or disease endotypes in the at-risk population.
  • 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;
  • 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 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;
  • Identify therapeutic targets in pathways that contribute to disease initiation and develop new classes of therapeutic molecules for preventative or early treatment strategies in at-risk individuals;
  • Explore the cellular and molecular basis for the heterogeneity of T1D etiology in the human population, including age-related endotypes, with the long-term goal of developing more targeted therapies.

As noted above, significant 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, human immune cells 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 or accelerated by the use of rodent models, the 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 during 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 PANC-DB open-source data repository for the cellular and molecular datasets generated by the Human Pancreas Analysis Program (https://hpap.pmacs.upenn.edu/ ) can also serve as a useful resource for both hypothesis generation and hypothesis validation.

The assembly of multidisciplinary teams under a single application to help address the complex 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  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

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed
New
Renewal

Renewal applications only from RFA-DK-19-024.

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit up to $3.5 million to fund 4-6 awards in FY 2024. The number of awards is contingent upon availability of funds and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to $550,000 in direct costs per year. Budgets are expected to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 4 years

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

Eligible Organizations

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
Foreign Institutions

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. 

Required Registrations

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.

Eligible Individuals (Program Director/Principal Investigator)

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: NIDDKletterofintent@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular 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:

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 any limitations of the proposed strategy and plans to address them;
  • Without duplicating information provided in the biosketches, provide a brief description of the multidisciplinary team if one exists and of the unique contribution of each team member to the project; describe the synergies that will result from the collaborations between investigative team members working across scientific areas and disciplines;
  • Proposed yearly milestones and expected opportunities for course-corrections based on emerging data generated in the proposed project;
  • Applicants should describe how their project could benefit from interactions and collaborations with their CBDS and HIRN colleagues, and how their proposed research will contribute to the overall scientific mission of CBDS and HIRN. CBDS's overall 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/or preventing the progression to autoimmunity. HIRN's overall mission is to support innovative and collaborative research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans.

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.

Applicants should describe how they plan to share reagents with their CBDS and HIRN colleagues, as well as with the larger scientific community.

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

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.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:
Overall Impact

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).

Scored Review Criteria

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.

 

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

Specific to this NOFO : How 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?

 

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

Specific to this NOFO: How 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?

 

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?

 

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

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

Specific to this NOFO: How clear are the projects focus 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?

 

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?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

 

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

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

 
 

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.

 

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

 

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.

 

Not applicable.

 

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

 

Not applicable.

Additional Review Considerations

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

 

Not Applicable

 

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).

 

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

 

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.

 

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 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.

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: 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:

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.

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.”

Cooperative Agreement Terms and Conditions of Award

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 Funding Opportunity Announcement (NOFO) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
  • Recipient(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.
  • Recipients are responsible for their staff in maintaining confidentiality of the information as developed by the CBDS, 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 CBDS consortium including the Human Islet Research Enhancement Center (HIREC) and the designated NIH staff (e.g., Program Official, Project Scientist, Project Coordinator).
  • Recipient(s) agree to establish agreements amongst themselves that address the following issues: (1) procedures for data sharing among network/consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the network/consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing bio-specimens under an overarching Material Transfer Agreement (MTA) amongst network/consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
  •  Any third-party collaboration (including but not limited to interactions with organizations from industry, academia, and nonprofit institutions) should be governed by a research collaboration agreement (e.g., Clinical Trial Agreement, Research Collaborative Agreement, etc.) or any third-party contract mechanism(s) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures, applicable network/consortium policies, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network/consortium studies between 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/consortium policies. Further, at the request of the NIDDK Program staff, any other network/consortium-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: “Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions)”, and Section 8.5.2, titled: “Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support”, noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.”
  • Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and network/consortium activities that includes access to any network/consortium generated resources (i.e., data and biosamples), or study results that are not publicly available, or using the name of the network/consortium or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.
  • Recipients must agree to comply with the processes and goals as delineated within the NOFO.
  • Recipient(s) agree to the governance of the CBDS 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 Recipient will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and subcommittees.
    • Recipients must serve on Subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator’s Retreat.

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

The NIDDK will designate program staff, including a Program Official and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award (NOA).

An NIH IC Project Scientist [or Project Coordinator, or Project Collaborator] will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows:

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

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

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

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

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

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

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

d. The NIDDK Project Scientist or Project Coordinator may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

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

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

Areas of Joint Responsibility include:

Through the CBDS recipients, CBDS Steering Committee, Trans-Network Committee and NIH staff, the study members 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 NOFO.

A face-to-face meeting of HIRN and a minimum of 2 CBDS meetings (teleconference or face-to-face meetings) will be required annually.  CBDS recipients, the CBDS Project Scientist, and the CBDS Program Official will be expected to attend the required meetings.

HIRN Trans-Network Committee (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, CTAR, CMAI, CBDS, and HPAC);
  • The HIRN-TNC is not a governing body and does not cast votes.
  • The HIRN-TNC will facilitate communication and foster collaboration across the different consortia.
  • The HIRN-TNC will be responsible for organizing the yearly HIRN Scientific Investigator’s Retreat.
  • The HIRN-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 HIRN members through in-person, electronic, or teleconference meetings, which will be approved by the HIRN-TNC.
  • The HIRN-TNC will have meetings that will be organized by the PD/PI of the HIREC,
  • Any HIRN-TNC member may place items on the agenda. These should be communicated in advance of the meeting to the Project Scientist(s) who will distribute these to all members.  The designated NIDDK Program Official(s) of the various HIRN consortia may be asked to participate in order to provide additional information and to summarize actions that are taken.

CBDS Steering Committee (SC)

  • A Steering Committee organized by the study investigator(s) will be the main governing body of the CBDS.
  • The CBDS-Steering Committee(SC) 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 CBDS-SC. The CBDS-SC will document progress in written reports to the NIDDK Program Official and will provide periodic supplementary reports upon request.
  • The CBDS-SC will be composed of all CBDS PDs/PIs 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 CBDS-SC meetings will be dictated by a vote of the members of the CBDS-SC.  The NIDDK Program Official may serve as a non-voting member on the Steering Committee.
  • A Chairperson of the CBDS-SC will be selected and voted on by the CBDS-SC members.  The Chairperson provides leadership to the Committee by conducting the CBDS-SC 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 conerns regarding potential for bias and/or conflict of interest or lack of required expertise.

External Consultants

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

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution 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 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 DHHS 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.

Application Submission Contacts

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

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

Scientific/Research Contact(s)

Olivier Blondel, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-263-4342
Email: blondelol@niddk.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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

Authority and Regulations

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

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

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