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
Human Islet Research Network - Consortium on Targeting and Regeneration (HIRN-CTAR) (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
Reissue of RFA-DK-18-014
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-DK-22-009
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.847
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications for the Consortium on Targeting and Regeneration (CTAR) that supports the development of innovative strategies to increase or protect functional human beta cell mass in patients with Type-1 Diabetes (T1D) through controlled manipulation of beta cell replication or islet cell plasticity, reprogramming of non-beta cells into beta-like cells, or shielding of residual beta cell mass from the autoimmune environment. CTAR is part of the Human Islet Research Network (HIRN).

Key Dates

Posted Date
July 13, 2022
Open Date (Earliest Submission Date)
September 26, 2022
Letter of Intent Due Date(s)

September 26, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 26, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

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.

Expiration Date
October 27, 2022
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 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.

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. Funding Opportunity Description

Purpose

 

This Funding Opportunity Announcement (FOA) invites cooperative agreement applications for projects to develop strategies to target the human pancreatic environment in-vivo to deliver regulatory cells, molecules or gene constructs that can protect or replenish functional beta cell mass, or to engineer cellular or synthetic sentinel biomarkers that can safely monitor the islet tissue environment in individuals at risk of developing Type-1 Diabetes (T1D).

 

Background

 

T1D is characterized by the development of an autoimmune response that leads to the specific destruction of the pancreatic beta cells. While some progress has been made in recent years to partially protect residual beta cell mass in recently-diagnosed individuals and to measure disease progression in patients with T1D with sub-optimal sensitivity, strategies for initiating, maintaining and monitoring a  full arrest of disease progression are still needed. In addition, in spite of the encouraging identification of molecules that may have an impact on beta cell replication, robust and safe therapeutic strategies to replenish or protect beta cell mass in patients with T1D have yet to be developed.

The promising outcome of cadaveric islet transplantation has demonstrated that beta cell replacement can be therapeutic for the treatment of T1D. It has prompted the search for alternative and abundant sources of beta cells for replacement therapy, and much progress has been made in differentiating insulin-producing cells from stem/progenitor cells for possible clinical use. At the same time, our rapidly evolving knowledge in areas such as islet-cell plasticity, epigenetic control of cell identity, cellular reprogramming, genome editing, gene therapy, synthetic biology and engineering of therapeutic compounds with cell-specific properties could be leveraged to develop therapeutic alternatives to islet transplantation. Such strategies include the safe and controlled replenishment of functional beta cell mass in-situ using non-beta cells as a cell source, or the protection of residual beta cell mass following systemic delivery of islet-specific immunomodulatory agents, engineered cells, or protective gene constructs.

 

Research Opportunities and Scope

 

This Funding Opportunity Announcement encourages the development of innovative tools and strategies for the therapeutic targeting of relevant cell types with the long-term goal of protecting or replenishing functional beta cell mass in patients with T1D, or for the non-invasive monitoring of the islet environment in individuals at risk of developing T1D or diagnosed with the disease. Relevant strategies could include (but are not restricted to):

  • Identify islet cell surface anchors to facilitate the targeted delivery of therapeutic compounds; use next-generation proteomics analyses to explore understudied features of islet cell surfaceomes, including cell-specific posttranslational modification (PTMs); use systematic analysis of T-cell clones isolated from patients with T1D to identify beta cell specific PTMs.
  • Build novel screening platforms to identify human islet cell-specific ligand from molecular libraries; develop alternative methodologies for protein ligand discovery, including DNA-encoded chemical libraries (DELs).
  • Develop tools for in vivo delivery of regulatory cargos to the human islet environment, including molecular complexes that can facilitate the safe, efficient, and specific delivery of small molecules, regulatory RNAs or gene constructs to human beta cells or the diabetic islet environment.
  • Develop screening platforms to discover small molecules that can alter intracellular interactomes and regulatory pathways involved in beta-cell stress, death, senescence, regeneration or immunogenicity; develop novel synthetic compounds to target these pathways, including cell-permeable bifunctional small molecules to influence protein homeostasis or protein function (proteolysis-targeting chimeras, inducible degrons, chemical inducers of proximity, molecular glues, etc.).
  • Develop beta cell-specific chemistries, such as designer prodrugs that are only activated within the human beta cell or within the diseased pancreatic islet environment.
  • Further develop and apply gene therapy approaches for the pancreatic islet environment; build on recent progress in capsid design and cell-specific promoter constructs to develop safe and efficient strategies to protect or regenerate functional beta cell mass; validate feasibility, efficacy, and safety in relevant preclinical models.
  • Use knowledge of islet cell plasticity to replenish beta cell mass in situ, including through controlled differentiation of residual alpha cells into fully functional and immune-protected beta cells in T1D patients.
  • Develop strategies for the reprogramming of non-beta cells in-situ into glucose-regulated, insulin-secreting beta-like cells; explore the potential of these beta-like cells to regulate glucose homeostasis in vivo; explore the immunogenicity of reprogrammed beta-like cells in disease models closely resembling human T1D.
  • Engineer immune-privileged beta cells in-vivo: strategies could include expression of gene products that are not naturally expressed in adult beta cells, such as proteins used by viruses, parasites, or cancer cells to evade surveillance by peripheral immune cells.
  • Develop strategies to target pancreatic non-beta cells to improve the diseased islet environment, and/or to engineer paracrine activities aimed at regenerating or protecting functional beta cell mass.
  • Engineer patient-derived immune cells with specific cell-homing properties and the ability to deliver therapeutic or immunomodulatory agents to the human islet compartment, including nonendogenous regulatory proteins or molecules.
  • Engineer safe, sensitive and specific synthetic or cell-based biomarkers that can report on the state of the islet environment in individuals at risk of developing T1D
  • Drive therapeutic strategies closer to clinical testing; improve the safety and efficacy of beta cell regenerative or immune-protective strategies currently under development towards first-in-man studies, including assessment of PK/PD, biodistribution and potential off-target effects of candidate targeting agents; take advantage of recently-developed in-vitro platforms such as perifused/perfused islet biomimetics/islet-on-a-chip (with or without immune cells), or human pancreas tissue slices, to better assess therapeutic activity in a human cell/tissue system.


The long-term outcome of the projects proposed in response to the current initiative should be the development of safe and highly-specific products or reagents that could be administered orally or systemically to patients with T1D, at risk of developing T1D or with severe insulin deficiency unrelated to T1D, and could have a reasonable chance of being used in the clinic in the foreseeable future. To demonstrate the translational potential of their approach, applicants will need to validate within the funding period of the cooperative agreement the efficacy of the proposed therapeutic or diagnostic strategy in vivo using human cells or tissues (engraftment models), or large animal models that would be adequate for assessing efficacy and toxicity prior to first-in-human studies. Biological efficacy should be demonstrated following systemic, oral or surgical administration of the therapeutic or diagnostic agent in the relevant preclinical system.


Potential use of murine models: Given the important differences (genetic, developmental, morphological, cellular and molecular) that exist between the human and rodent islet environments, the use of human pancreatic tissues as a primary experimental system for the acquisition of new knowledge should form the basis of the applications written in response to this initiative. In situations where the efficient exploration of specific aspects of the pancreatic tissue or islet environment is greatly accelerated or facilitated by use of rodent models, limited use of rodent models is allowed if properly justified, but it is expected that results and hypotheses derived from these models will be validated in human tissues in a systematic fashion and throughout the funding period of the cooperative agreement.
 

Source of human cells and tissues: In choosing a source of human cells and tissues, applicants are encouraged to use high-quality repositories, biobanks and procurement networks, whether linked to NIDDK-funded clinical studies such as the Integrated Islet Distribution Program (https://iidp.coh.org/), the Diabetes Prevention Trial-Type 1 (DPT-1) or the Type 1 Diabetes Trialnet (https://repository.niddk.nih.gov/home/, or supported by private research efforts such as the JDRF nPOD (https://www.jdrfnpod.org/) or the T1D Exchange (http://www.t1dexchange.org/). If available, pancreata that are either densely genotyped (such as from NIH-supported the GTEx collection:https://commonfund.nih.gov/GTEx) or originating from donors with well-documented disease history or health records, should be used.

Composition of the applicant team: The assembly of multidisciplinary teams under a single application to help address the scientific challenges outlined in this initiative is encouraged, particularly to help combine complementary expertise (such as beta cell biology, immunology, virology, chemistry, synthetic biology, surgical expertise,access to human cadaver donors, etc.). Single-investigator applications from individuals with the required expertise to make a major contribution are also welcome.

NIDDK and the HIRN are 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

Successful applicants will join the Consortium on Targeting And Regeneration (CTAR) that was created in 2014 to support the development of innovative strategies to increase functional human beta cell mass in vivo through the controlled manipulation of beta cell replication or islet plasticity, or the reprogramming of adult non-beta cells into beta-like cells, or the protection of residual beta cell mass from autoimmune destruction in T1D [ RFA-DK-13-015: Consortium on Targeting And Regeneration (HIRN-CTAR) UC4 ]. CTAR is one of the five consortia that constitute the Human Islet Research Network (HIRN), created in 2014 to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans.

Successful applicants will be expected to work collaboratively with all of their CTAR 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 CTAR investigators are expected to be made available to the research community, as appropriate and consistent with achieving the goals of the program. All participants will be expected to adhere to the sharing policies developed by the HIRN as a term of the award. CTAR Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must participate in the annual HIRN Investigator Scientific Retreat, as well as in CTAR Steering Committee teleconferences to be held at least bi-annually. All participants will be obligated to abide by the policies adopted the majority vote of the CTAR Steering Committee and the HIRN Trans-Network Committee (see "Cooperative Agreement Terms and Conditions of Award, Section VI.2.).
 

Applications Not Responsive to this FOA

  • Projects that are mostly focused on developing delivery vehicles or cell-targeting strategies need to demonstrate efficacy of delivery to the human islet environment in-vivo using biological or imaging-based readouts.
  • Projects that are exclusively focused on developing new imaging-based strategies for in-vivo monitoring of beta cell mass or function are not responsive to this FOA. However, the use of imaging-based reporter systems to validate in-vivo efficacy of new islet-targeting strategies is considered responsive.


NIDDK Strategic Plan for Research

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 FOA.

Application Types Allowed
New

Renewal applications from RFA-DK-18-014

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 FOA.

Clinical Trial?

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

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $3.75 million for FY 2023 to fund 4-6 awards.

Award Budget

Application budgets are limited to $600,000 direct costs per year.

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 FOA.

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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • System for Award Management (SAM)– Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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 his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. 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 FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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 FOA.

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:

In addition to describing the details of their research strategy, applicants should specifically document the following characteristics of their project:


General:

  • Provide a detailed description of the rationale for the proposed research strategy, based on preliminary data;
  • Describe any limitations of the proposed strategy and plans to address them;
  • Describe how the efficacy of the proposed therapeutic or diagnostic strategy will be validated in vivo using human cells or tissues (engraftment models), or large animal preclinical models.
  • Proposed yearly milestones and expected opportunities for course-corrections based on emerging data generated in the proposed project;
  • If a multidisciplinary team is assembled for the project: without duplicating information provided in the biosketches, provide a brief description of the multidisciplinary team 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;


Biological validation:

  • For projects that are focused on developing cell-targeting strategies, applicants should describe how they will demonstrate efficacy and specificity of delivery to a human islet environment;
  • For projects that are proposing to discover or to develop novel diagnostic or therapeutic strategies, applicants need to indicate how they will validate the biological efficacy of the approach using live human cells,tissues or clinical samples;


Innovation and significance:

  • All applicants should characterize the level of novelty of their proposed approach compared to similar efforts in the field, and the impact that their targeted strategy and/or project will have on T1D research, diagnosis and/or treatment;
  • All applicants should describe the near-term and long-term contribution of their proposed approach to the development of safe and efficient therapeutic or diagnostic tools, and whether these have a reasonable chance of being used in the clinic;


Contribution to the HIRN effort:

  • Applicants should describe how their project could benefit from interactions and collaborations with their CTAR and HIRN colleagues, and how their proposed research will contribute to the overall scientific mission of CTAR and HIRN. CTAR's overall mission is to support the development of innovative strategies to increase or protect functional human beta cell mass in patients with Type-1 Diabetes (T1D) through the controlled manipulation of beta cell replication, islet cell plasticity, and the reprogramming of pancreatic non-beta cells into beta-like cells, or through shielding the residual beta cell mass from the autoimmune environment. 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. Information about HIRN and CTAR can be found on the HIRN public portal at https://hirnetwork.org/ .

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

The following modifications also apply:

Applicants are expected to register resources supported by this FOA with the NIDDK Information Network (dkNET) at https://dknet.org/ and use Research Resource Identifiers (RRID) assigned through dkNET in any publication supported by this FOA.

Appendix:

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (https://www.nlm.nih.gov/cde/index.html) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

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

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 FOA: How will the proposed project help with the development of safe and efficient therapeutic or diagnostic tools for T1D in the medium to long term?

 

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 clear is the description of the role and contribution of each independent member of the investigative team?

 

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?

Specific to this FOA: How innovative is the proposed strategy to target the islet compartment in-situ ?

 

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 FOA: How appropriate is the investigator’s plan to assess the efficacy and specificity of their targeting of the human islet environment in an in-vitro setting? How well have the investigators described how their project could benefit from interactions with their HIRN colleagues, and how their application would contribute to the overall mission of CTAR and HIRN?

 

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.

 

Not applicable.

 

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 Animal 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.

 

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.

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 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).

 

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 convened by NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 recipient's business official.

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

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

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

2. Administrative and National Policy Requirements

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

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

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 OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, 2 CFR 200 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 CTAR 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 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 CTAR recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

 

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

  • The CTAR 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 CTAR 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 CTAR Recipient will retain custody of and have primary rights to the data and software developed under these awards until time of publication, subject to Government policies regarding rights of access consistent with current HHS, PHS, and NIH/NIDDK policies.
  • All staff of the CTAR Recipient's team 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.
  • The CTAR Recipient 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 goals of the FOA.
  • All staff of the CTAR Recipient's team will be required to participate in a cooperative and interactive manner with NIH staff, one another and with the HIRN Administrative Hub (HIRN-AH) in all aspects of CTAR.
  • The CTAR Recipient is expected to share data, materials, models, methods, information and unique research resources that are generated by the projects in accordance with CTAR policies in order to facilitate progress. When appropriate, and in accordance with NIH policies, the CTAR Recipient 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 CTAR members.
  • The CTAR Recipient will submit a list of milestones and project deliverables to the HIRN-AH prior to the initial HIRN meeting, and will update this list annually.
  • The CTAR Recipient agrees 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. These agreements and issues will be provided to the NIDDK Program staff and the NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network policies.
  • The CTAR Recipient agrees that each industry collaboration should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures
  • The CTAR Recipient 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 CTAR Recipients is 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.
  • The CTAR Recipient agrees 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 CTAR Recipient will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees.
  • The CTAR Recipient must serve on CTAR subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator's Retreat.
  • The CTAR Recipient 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, as described below:

  • The NIDDK will designate program staff, including a Program Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.
  • The NIH will invite experts with relevant scientific expertise to provide feedback to the NIH on CTAR 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 coordinate and facilitate the research projects, attend and participate in all meetings of the CTAR, and act as a liaison between the CTAR Recipient 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 CTAR. 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 CTAR. Review of progress may include regular communications between the Principal Investigator/Program Director and NIH staff, periodic site visits for discussions with the CTAR Recipient's research team, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
  • The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or CTAR 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 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 CTAR 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 will have substantial scientific programmatic involvement in research coordination and performance monitoring. The dominant role and primary responsibility for these activities resides with the CTAR Recipient, however, specific tasks and activities in carrying out the studies will be shared among the CTAR Recipients and the NIH Project Scientist.
  • The NIH Project Scientist serves as a resource with respect to other ongoing NIH activities that may be relevant to CTAR studies to facilitate compatibility and avoid unnecessary duplication of effort.
  • The NIH Project Scientist or designee may coordinate activities among CTAR recipients by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data and in the publication of results.
  • The NIH Project Scientist may review procedures for assessing data quality and monitor study performance.
  • The NIH Project Scientist may be a co-author on study publications. In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.


Areas of Joint Responsibility include:

  • Through the CTAR recipients and NIH staff, CTAR will cooperatively develop and implement processes to submit information and data to the HIRN-AH, 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 CTAR meetings (teleconferences or face-to face meetings) annually. CTAR recipients, the CTAR Project Scientist, and the CTAR Program Official are expected to attend these meetings. One of these bi-annual meetings could be combined with the annual HIRN Investigator Scientific Retreat.


Steering Committee:

The CTAR Recipient agree to the governance of the CTAR through a Steering Committee.

  • On an annual basis, a Chairperson will be selected by the CTAR Steering Committee. The Chairperson will be in charge of facilitating the CTAR Steering Committee meetings and teleconferences. In collaboration with the HIRN-AH and the NIH Project Scientist, the Chairperson is responsible for coordinating the Steering Committee activities, for preparing meeting agendas and for chairing meetings. The NIDDK Project Scientist may not serve as Chairperson. The NIDDK Program Official shall be consulted regarding the selection of the Chairperson and will have the option to veto the selection based on specific concerns regarding potential for bias or conflict of interest or lack of required expertise. The NIDDK Division of Extramural Activities Director and the Deputy Director of NIDDK will consider the merit of the basis for the veto and the veto shall only be enforced with their concurrence. If either the NIDDK Division of Extramural Activities Director or the Deputy Director of NIDDK have a conflict of interest associated with the decision, then the decision will be made by the individual who is not in conflict in consultation with the NIDDK Director.
  • 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 CTAR recipients 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 CTAR 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 CTAR Recipient will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees. CTAR recipients must serve on CTAR 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 HIRN-AH and the Steering Committee Chairs and Project Scientists of the HIRN scientific topic consortia (CHIB, CTAR, CMAI, CBDS 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 HIRN-AH. 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 CTAR members through in-person, electronic, or teleconference meetings, as appropriate. The HIRN-AH 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 CTAR Steering Committee and meet by teleconference with the CTAR Steering Committee at least once a year. The CTAR-ESP will be updated on progress and give feedback to the CTAR Steering Committee on adjustments and future directions for the CTAR research projects. On an annual basis, and following input from the ESP members, the CTAR Steering Committee will appoint an ESP Chair who will be required to attend the annual HIRN Investigator Scientific Retreat, to participate to the CTAR Steering Committee meetings as ex-officio, and to serve as the CTAR-ESP representative to the larger HIRN-ESP that will also meet once a year. The CTAR ESP Chair will be tasked with relaying the CTAR Steering Committee recommendations for new Opportunity Funds Initiatives to the HIRN-ESP. All CTAR-ESP members will also be invited to listen as ex-officio to CTAR Steering Committee meetings. Members of the CTAR-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 HIRN-AH will support costs for teleconferences between the ESP and the CTAR Steering Committee, will arrange the CTAR-ESP and HIRN-ESP teleconferences, maintain a record of minutes, and support costs for the CTAR-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 CTAR Recipient. This special dispute resolution procedures in no way affect the CTAR Recipient's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

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: 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: 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)

Elena Sanovich, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8886
Email: sanoviche@mail.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 FOA is supported under the authority of P.L. 116-260, Consolidated Appropriations Act, 2021; Section 302. Diabetes Programs

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