Part 1. Overview Information

Key Dates

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Over 37.3 million adults in the U.S. have diabetes mellitus (DM), and 96 million adults with prediabetes are at increased risk for developing type 2 diabetes mellitus (T2D). There is considerable heterogeneity in the development and clinical presentation of DM in this broad patient population. Responses to pharmacologic therapy and the development and progression of complications from diabetes can also vary among patients. Our lack of understanding of this heterogeneity hinders the goal toward effective translation of precision medicine in diabetes care.

Diabetes has been traditionally classified as either type 1 or type 2 diabetes. However, other subtypes of diabetes, such as latent autoimmune diabetes in adults (LADA), congenital generalized lipodystrophy, Wolfram syndrome, neonatal/congenital diabetes, and maturity-onset diabetes in the young (MODY) have been studied, characterized and are now recognized. An even greater range of unrecognized phenotypes for diabetes likely exists and recent publications have suggested many additional sub-types.

The identification and study of new cases of rare or atypical forms of diabetes may yield greater insight into the heterogeneity of more common forms of T2D. Detailed phenotyping of these individuals and their families may help to characterize milder subtypes present in the spectrum of T2D in the general population and reveal novel mechanistic pathways involved in the prevention and/or treatment of T2D. Studying the underlying genetic background of these individuals may lead to the identification of function for the polymorphisms in or near known T2D genes and explain the contribution of specific loci to aspects of polygenic T2D. These genetic and phenotypic studies may help in identifying new biomarkers for screening and diagnosis. Furthermore, genetic studies may help to identify drug targets and catalyze the development of therapies for use, not only by these individuals with rare/atypical forms of diabetes, but also in subtypes of T2D in the general population. In addition, RADIANT will generate a repository of samples and data to enable all interested researchers to study and elucidate atypical forms of T2D. Dedicated efforts to discover and study rare/atypical forms of diabetes will not only aid individuals directly by informing their pathogenesis and treatment, but also address the heterogeneity of T2D seen in the broader populations by providing new insights on mechanisms, diagnoses, and treatments for T2D.

Purpose and Center Objectives

The purpose of this funding opportunity is to invite applications from the two currently funded Rare and Atypical DIAbetes NeTwork (RADIANT) research centers to continue and expand their study of rare and atypical forms of DM. These centers will continue to identify and analyze phenotypic and genotypic defects that may provide insights into more common, heterogeneous forms of DM in the general population. RADIANT will also continue to develop community resources to advance research in this area through the collection and dissemination of data and samples for access by the broad research community.

To accomplish these goals, the RADIANT lead research centers should:

(1) Establish precision diagnoses for new Mendelian forms of DM by enrolling family members of individuals already enrolled in RADIANT who have a family history supporting a Mendelian form of DM.

(2) Plan and implement in vitro and basic studies leveraging induced pluripotent stem cells (iPSCs) differentiated into tissues of interest to establish pathogenicity of potential causal variants.

(3) Continue to build/expand and manage a database and biospecimen repository for storage of data and samples from individuals with rare/atypical forms of DM for future analyses.

Overview

The two currently funded (lead) RADIANT research centers should jointly be at the forefront of the national effort to identify and study rare/atypical forms of DM. These lead centers must propose coordinated administrative plans to oversee all consortium activities, manage resources, monitor progress, ensure compliance with human subject protections, and achieve proposed goals. The centers as part of this initiative must continue to utilize a central IRB for all RADIANT research projects. To achieve the objectives above, the lead centers should continue to have (1) a Discovery Team to identify and study individuals/families with rare/atypical forms of DM, (2) an Adjudication Committee to critically review cases, and (3) a Database and Biorepository Core to organize and store data and biospecimens for use in future research and data analyses.

The two lead RADIANT research centers must have expertise and a track record of productivity and peer-reviewed research funding in diabetes, genetics, and/or rare diseases. The research environment must be able to support approaches for deep phenotyping and genetic analyses of rare/atypical forms of diabetes at the applicant institution and/or collaborating institutions. Lead RADIANT research centers will be responsible for enlisting affiliate research centers to contribute to RADIANT recruitment, enrollment and studies. The affiliate centers should include investigators with expertise in the study of rare and atypical forms of DM and should be located in geographic locations that are conducive to recruitment of individuals with atypical diabetes, particularly in areas serving underrepresented minority populations. The NIDDK strongly encourages research on sex/gender differences, sexual and gender minority-related research and race/ethnic diversity (see NOT-DK-22-003). This funding opportunity announcement (FOA) aligns with the mission and vision of the NIDDK Strategic Plan for Research (https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/niddk-strategic-plan-for-research), including the theme of empowering a multidisciplinary workforce, engaging diverse stakeholders (from a range of different social, racial and ethnic backgrounds as well as different genders, ages and sexual orientations), and pursuing pathways to health for all. Specifically, this FOA aligns with the scientific goals (e.g. 1.2 and 3.3) and cross-cutting topics (e.g. women’s health) of the NIDDK Strategic Plan for Research.

Application Components

Overall

A Steering Committee will be formed to provide direction and coordinate RADIANT activities. This group will establish procedures for RADIANT function. Once yearly, the Steering Committee and other key personnel are expected to convene at a meeting to review scientific progress, highlight key RADIANT activities, and communicate with NIDDK staff. An Observational Study Monitoring Board (OSMB), convened by NIDDK, will review study progress, safety data and interim results as appropriate, and will provide guidance to NIDDK.

Administrative Core

The RADIANT Administrative Core is responsible for managing resources, establishing and maintaining a central IRB for research projects, and overseeing progress on all RADIANT activities. The Administrative Core must be able to initiate and utilize collaborations between investigators throughout the world, medical and professional societies, patient advocacy groups, and rare disease networks nationally and internationally. Additional outreach should be undertaken to raise awareness of research efforts, disseminate research progress, and foster translation and application of research findings to the broader community of individuals with type 2 diabetes. As part of this outreach effort, a RADIANT website must be created and maintained.

Data and Repository Core

Rare diseases are generally considered conditions or disorders affecting less than 200,000 individuals in the U.S. The strategy for accomplishing more rigorous research on rare phenotypes requires efforts to accumulate data and biospecimens from groups of individuals with the same rare phenotype for further coordinated analyses. Therefore, RADIANT must create and manage a Data and Biospecimen Repository Core to store clinical and demographic information as well as biospecimens. This Data and Biospecimen Repository Core must manage the collection and centralized storage of data and biospecimens and have processes for sharing and tracking shared data and biospecimens.

Discovery and Analysis Project

RADIANT must have a Discovery and Analysis Project that is responsible for developing strategies and plans to identify, recruit and study individuals/families with new, rare/atypical forms of diabetes. The discovery of individuals/families with new, rare/atypical forms of diabetes can involve direct contact with individuals (e.g. patient contact registry), solicitations to care providers (e.g. outreach via professional societies), and/or institution-based mechanisms (e.g. network of diabetes clinics). There should be a unified plan for studying these individuals, and this plan should contain common elements of an individual’s history, demographics, physical exam, social history, family history, critical laboratory tests, and genomic data that will be captured in a systematic fashion on all individuals. The Discovery and Analysis Project should ensure compatibility and comparability of data collected for future larger-scale analyses.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

This FOA is limited to the two current RADIANT awardees supported under RFA-DK-17-006.

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

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

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH 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 Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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 or an institutional system-to-system solution. A button to apply using ASSIST is 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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, current RADIANT awardees 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, PhD
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: [email protected]

Page Limitations

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

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

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.

Overall Component

When preparing your application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project Summary/Abstract: Describe the goals and objectives of RADIANT and how these contribute to accomplishing the overall goal to improve the understanding, prevention, and treatment of the broader, heterogeneous population with type 2 diabetes. Explain the overall strategy for achieving the goals of RADIANT. Provide an overview of the structure of RADIANT.

Project Narrative: Describe the relevance of the research fostered by RADIANT activities on public health in 1-3 sentences.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

• In the Project Directors/Principal Investigators section of the form, use Project Role of Other with Category of Center Directors and provide a valid eRA Commons ID in the Credential field.
• The Center Directors must demonstrate leadership ability and skills to direct large multicenter projects. The Center Directors should also have extensive clinical research experience and expertise in diabetes, genetics and/or rare diseases.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

Each PD/PI must devote a minimum of 1.2 calendar months per year to RADIANT through the individual components.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe specific aims with the goal of further identifying and studying individuals/families with new/atypical forms of diabetes.

Describe RADIANT's short- and long-term goals and discuss how these goals will be achieved. Discuss how the expected outcomes will address RADIANT's objectives as listed in Section 1. Funding Opportunity Description.

Research Strategy

Progress Report

A progress report is required for this renewal application and should be included in the overall Research Strategy section. The progress report should summarize the aims of the previous project period and the importance of the findings and should emphasize how these findings contributed toward achievements. Any significant changes to the aims should be discussed. The progress report should include discussion of the inclusion of underrepresented minority individuals as well as women and children in the various study Stages (see NIH Inclusion Policies).

The progress report should focus on progress made toward achievement of recruitment milestones during the first grant cycle, including the number of participants screened, enrolled and evaluated during Stages 1, 2 and 3 of the study with details regarding screening, enrollment, evaluation and retention. Stage 1 includes screening evaluation for possible cases of atypical diabetes, Stage 2 includes whole genome sequencing of those determined to be eligible during Stage 1, and Stage 3 includes those participants who underwent deeper phenotypic analysis.

Operation and Organization

Describe the organizational framework and include any relevant charts/diagrams. Explain the process for establishing relevant committee and programs and how they will function both independently and jointly. Describe the selection process for committee roles. Describe the qualifications of needed external advisors and consultants. Outline plans to leverage resources from other NIH-funded centers (such as the Undiagnosed Diseases Network).

Discovery

Describe RADIANT's overall strategy for continuing to identify individuals with new rare/atypical forms of diabetes for further study. Particular attention should be paid to a detailed description of how RADIANT will be inclusive and will address the recruitment of underrepresented minority populations. Outline the various modalities of outreach that will be implemented to discover these new/atypical forms of diabetes and approach to contacting potentially affected family members of previously enrolled participants with a family history suggestive of a Mendelian form of diabetes to aid in identifying potential causal variants. Resources available for identifying and studying individuals should be described. Provide estimates of approximately how many individuals/families have been and will be identified for study using the planned methods of outreach. Describe the procedure that will be used to determine which individuals/families will be chosen for more in-depth study. Explain when and how individuals/families will be consented for further study, and when and how RADIANT staff will interact with individuals/families with rare/atypical forms of diabetes. Discuss the process for continuing to develop community resources to advance research in this area through the collection of data and samples for access by the broad research community.

Analysis

Describe RADIANT's plan for studying individuals/families with rare/atypical forms of diabetes. Delineate where and by whom the individuals/families will be studied. Explain how and when RADIANT will provide resources and services for studying these individuals. Include details on common elements of an individual's history, demographics, family history, social history, physical exam findings, critical laboratory test results and genomic data that will be collected in a systematic fashion on all individuals/families with rare/atypical diabetes. Describe plans to ensure compatibility and comparability of data to be collected for future larger-scale analyses. Explain how the current planned and future studies on these individuals will contribute to the overall goals of the project. Describe how RADIANT will establish precision diagnoses for new Mendelian forms of diabetes by enrolling family members of previously enrolled participants with a family history suggestive of a Mendelian form of diabetes to aid in identifying potential causal variants. Discuss how RADIANT will perform in vitro and basic studies leveraging induced pluripotent stem cells differentiated into tissues of interest to establish pathogenicity of potential causal variants. Describe how RADIANT will accomplish phenotypic characterization and will study the clinical course of oligogenic/polygenic forms of atypical diabetes by continuing recruitment and studies of people with rare/atypical diabetes.

Letters of Support:

Provide letters of support for the proposed Center by appropriate institutional officials. Letters should address commitment of the parent organization, or any of its partners, to RADIANT and its goals. The parent institution is expected to recognize RADIANT as a formal organizational component and provide documented evidence of space dedicated to the needs of RADIANT, protected time to devote to RADIANT activities, staff recruitment, dedicated equipment, or other financial support for RADIANT. The parent institution should provide assurance of its commitment to continuing support of RADIANT in the event of a change in directorship and a well-defined plan for this eventuality should be in place. Both the institution and pertinent departments must show a strong commitment to supporting RADIANT.

If collaborative linkages are being developed between RADIANT and other local NIH funded centers in related areas (e.g., Diabetes Research Center or Clinical and Translational Science Award), a letter of agreement from the collaborating Center PD(s)/PI(s) should be included.

Do not provide letters of support from individuals who will not be involved in RADIANT's research activities.

Resource Sharing Plan:

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.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

Do not use the Appendix to circumvent page limits.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

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 (Overall)

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

ADMINISTRATIVE CORE

When preparing your application, use Component Type 'Administrative Core'.

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: Describe the existing environment, facilities, and resources available for use by the Administrative Core. RADIANT is strongly encouraged to enter into agreements with cores already established within their institution, or with other Centers in close proximity, when the existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. Explain the process (including fee structure) to utilize the facilities and resources. Institutional resources capable of supporting the research endeavors must be made evident.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Administrative Core Director and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

The Administrative Core Director must demonstrate leadership ability and skills to direct large multicenter projects. The Administrative Core Director should also have extensive clinical research experience. Expertise in diabetes, genetics, or rare diseases is preferred; however, it is acceptable for other members of the leadership team to provide knowledge in these content areas if the Administrative Core Director lacks this background.

An Acting Administrative Core Director must be identified to serve in the absence of the Administrative Core Director.

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

Personnel: The Administrative Core Director must devote a minimum of 1.2 person months to the Administrative Core. If a multiple-PD/PI application, the combined effort of the PD(s)/PI(s) must be 2.4 person months.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Travel: Include travel costs for the PIs/PDs, Core Directors, and pertinent Collaborators to attend an annual RADIANT scientific meeting held every 12-18 months in the Bethesda area. Include travel costs for Observational Study Monitoring Board members to travel to an annual meeting. If well-justified and related directly to program activities/functions, limited travel funds for key professional staff may be requested to support travel to other sites for training or collaborative research. This should be included in the Administrative Core budget and not in this section.

Supplies: Consumable supplies directly related to the operational aspects of the Administrative Core facilities are an allowable expense.

Consultants: Include costs associated with consultants (consultant fees, per diem, teleconferences, and travel) when their services are required by RADIANT.

Other Expenses: Funds for supporting the RADIANT website may be requested.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Specific Aims: State how the Administrative Core will contribute to the goals of RADIANT and outline interactions of the Administrative Core with other Cores/Programs/Committees. Provide an overview of how the Administrative Core will set the overall direction of RADIANT and ensure optimal utilization of RADIANT resources.

Research Strategy:

A clear plan should describe and address how and which members of the administrative team will oversee resources, coordinate interactions, and review progress of key RADIANT components and activities. This plan should outline policies and procedures that will be established for this purpose and when they will be modified. Strategies to mitigate and resolve disputes should be outlined.

A central IRB is a necessary aspect to the operation of research within RADIANT. The structure, functioning, and membership of this central IRB need to be clearly described, and policies and procedures for this entity outlined.

To build the research capacity for identifying and studying rare/atypical forms of diabetes, RADIANT must demonstrate its capability of and plans to forge collaborations with outside clinicians and investigators, healthcare systems and institutions, professional/medical societies, patient advocacy groups, and other rare disease efforts nationally and internationally. Details on the creation and maintenance of a website for RADIANT as part of these efforts must be provided. Furthermore, RADIANT must describe its outreach strategy to raise awareness on research efforts, disseminate research findings, and foster translation and application of research findings to the broader research and clinical community.

If external Advisors/Consultants are needed, describe their qualifications and function. Do NOT provide names or biosketches for advisors/consultants.

Letters of Support: Include any relevant letters of support, as needed. Do not provide letters of support from individuals who will not be involved in RADIANT's research activities.

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, with the following modification:

Generally, Resource Sharing Plans are expected, but they are not applicable for this component.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Administrative Core) there are duplicate entries

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.

DATABASE AND REPOSITORY CORE

When preparing your application, use Component Type 'Database and Repository Core'.

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

SF424 (R&R) Cover (Database and Repository Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Database and Repository Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Database and Repository Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete.

Facilities and Other Resources: Describe the existing environment, facilities, and resources available for use by the Database and Repository Core. Explain the process (including fee structure) to utilize the facilities and resources. Institutional resources capable of supporting the research endeavors must be made evident.

Project /Performance Site Location(s) (Database and Repository Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Database and Repository Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Director' and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

The Core Director must have leadership and organizational skills to guide in the collection, processing, analysis and distribution of human tissues and samples. The Core Director and his/her team must also have experience in developing and integrating databases from different experimental modalities. They must also have the skills to develop community data portals for providing open access summary data and accepting data use requests by the broader research community.

An Acting Database and Repository Core Director must be identified to serve in the absence of the Database and Repository Core Director.

Budget (Database and Repository Core)

Budget forms appropriate for the specific component will be included in the application package.

Personnel: The Core Director must dedicate at minimum 1.2 person months to this Project.

Equipment: A general listing of shared pieces of equipment to be used for Center activities should be provided, and the process (including fee structure) for using the equipment should be described. If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase.

Travel: Travel costs for the Core Director to attend annual Center scientific meeting held every 12-18 months in the Bethesda area should be included in the Administrative Core budget and not in this section. If well-justified and related directly to Program activities/functions, limited travel funds for key professional staff may be requested to support travel to other sites for training or collaborative research. Funds for investigators and staff to attend national or international scientific meetings or workshops may not be requested.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Database and Repository Core)

Specific Aims: Describe the aims of this Core to support the goal of establishing and managing a database and repository of individuals/families with new/atypical forms of diabetes and facilitating the use of data and specimens for future study.

Research Strategy: The Database and Repository Core is another key aspect to accomplishing the mission of the Center. There are two main sections of this Core that require detailed plans.

Database

Describe the means for submitting and integrating data into a searchable data structure in a timely manner. Provide details on what data will be collected and stored. Explain how data will be curated and harmonized, instances where this is necessary, and how it will provide enhanced querying and analyses of data across individuals/families/phenotypes/disorders. Describe how a unique identifier for each subject will be assigned and utilized. Explain proposed methods and processes that will be set up to provide easy links to data from the same subject in multiple databases. Outline opportunities to link data from this database with related data that may be stored on other public databases (e.g. dbGaP, federated iPSC registries). Describe plans for providing a public, searchable catalog of open access data to encourage and facilitate use of data in the database for further analyses. Provide a detailed plan (including a timeline) for allowing, sharing, and tracking use of identifiable data. Plans to assure the security, privacy, and confidentiality of data in this database must be provided.

Repository

Provide plans and procedures for acquisition, shipping and receipt of biospecimens (e.g. blood, saliva, DNA, plasma, derived cell lines), and address how sample viability and integrity will be ensured. Outline specific biospecimen types and quantities that are planned as standard collections. Describe any flexibility for accepting additional biospecimens beyond what is planned. Describe procedures for processing and creating distributable biospecimen derivatives for future study. Provide plans and procedures for sample storage and distribution including biospecimen tracking and safeguards against accidental loss of biospecimens. Explain how variation in biospecimen collection, processing, and storage will be minimized. Describe plans to encourage and facilitate use of biospecimens for additional research and procedures for allowing, sharing, and tracking use of biospecimens.

Although NIDDK has a repository, it will not serve as the repository for the Center during the project period. Outline plans to continue the Center Database and Repository and to make data and specimens available to the broader research community after Center funding ends. If continuation of the Database and Repository is not feasible without Center funding, state plans to relinquish data and specimens to NIDDK.

Letters of Support: Include any letters of support for the Database and Repository Core, as relevant. Do not provide letters of support from individuals who will not be involved in the Center's research activities.

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, with the following modification:

Consistent with achieving the goals of this program, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program.

Applicants should discuss the following:

Availability of biological resources utilized and/or developed (cell lines, reporter systems, vectors, molecules, antibodies, biomarkers, etc.) as appropriate;

Availability of technologies and protocols developed with funds from this award as appropriate and consistent with achieving the goals of the program.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Database and Repository Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Database and Repository Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.

DISCOVERY AND ANALYSIS PROJECT

When preparing your application, use Component Type 'Discovery and Analysis Project'.

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

SF424 (R&R) Cover (Discovery and Analysis Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Discovery and Analysis Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Discovery and Analysis Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete.

Facilities and Other Resources: Describe the existing environment, facilities, and resources available for use by the Discovery and Analysis Project. RADIANT is strongly encouraged to enter into agreements with cores already established within their institution, or with other Centers in close proximity, when the existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. Explain the process (including fee structure) to utilize the facilities and resources. Institutional resources capable of supporting the research endeavors must be made evident.

Project /Performance Site Location(s) (Discovery and Analysis Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Discovery and Analysis Project)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Program Director and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

The Program Director must be a clinical investigator with experience in the study of individuals or families with rare diseases. Expertise in diabetes and/or genetics is preferred; however, it is acceptable for other senior key personnel involved in this Project to provide knowledge in these content areas if the Program Director lacks this background.

An Acting Discovery and Analysis Project Director must be identified to serve in the absence of the Discovery and Analysis Project Director.

Budget (Discovery and Analysis Project)

Budget forms appropriate for the specific component will be included in the application package.

Personnel: The Project Director must dedicate at minimum 1.2 person months to this Project. Salary support for postdoctoral students is not permitted.

Equipment: A general listing of shared pieces of equipment to be used for activities in the Discovery and Analysis Project should be provided, and the process (including fee structure) for using the equipment should be described. If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase.

Travel: Travel costs for the Project Director to attend an annual RADIANT scientific meeting held every 12-18 months in the Bethesda area should be included in the Administrative Core budget and not in this section. If well-justified and related directly to program activities/functions, limited travel funds for key professional staff may be requested to support travel to other sites for training or collaborative research. Funds for investigators and staff to attend national or international scientific meetings or workshops may not be requested.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Discovery and Analysis Project)

Specific Aims: Describe the aims of this Project to support the goal of identifying and studying individuals/families with new/atypical forms of diabetes.

Research Strategy: The Discovery and Analysis Project is a critical aspect to the mission of RADIANT. There are two main parts of this Project that require detailed plans.

Discovery

Describe RADIANT's overall strategy for continuing to identify individuals with new rare/atypical forms of diabetes for further study. Outline the various modalities of outreach that will be implemented to discover these new/atypical forms of diabetes and approach to contacting potentially affected family members of previously enrolled participants with a family history suggestive of a Mendelian form of diabetes to aid in identifying potential causal variants. Resources available for identifying and studying individuals should be described. Provide estimates of approximately how many individuals/families have been and will be identified for study using the planned methods of outreach. Describe the procedure that will be used to determine which individuals/families will be chosen for more in-depth study. Explain when and how individuals/families will be consented for further study, and when and how RADIANT staff will interact with individuals/families with rare/atypical forms of diabetes. Discuss the process for continuing to develop community resources to advance research in this area through the collection of data and samples for access by the broad research community.

Analysis

Describe RADIANT's plan for studying individuals/families with rare/atypical forms of diabetes. Delineate where and by whom the individuals/families will be studied. Explain how and when RADIANT will provide resources and services for studying these individuals. Include details on common elements of an individual's history, demographics, family history, social history, physical exam findings, critical laboratory test results and genomic data that will be collected in a systematic fashion on all individuals/families with rare/atypical diabetes. Describe plans to ensure compatibility and comparability of data to be collected for future larger-scale analyses. Explain how the current planned and future studies on these individuals will contribute to the overall goals of the project. Describe how RADIANT will establish precision diagnoses for new Mendelian forms of diabetes by enrolling family members of previously enrolled participants with a family history suggestive of a Mendelian form of diabetes to aid in identifying potential causal variants. Discuss how RADIANT will perform in vitro and basic studies leveraging induced pluripotent stem cells differentiated into tissues of interest to establish pathogenicity of potential causal variants. Describe how RADIANT will accomplish phenotypic characterization and will study the clinical course of oligogenic/polygenic forms of atypical diabetes by continuing recruitment and studies of people with rare/atypical diabetes.

Letters of Support: Include any letters of support for the Discovery and Analysis Project, as relevant. Do not provide letters of support from individuals who will not be involved in RADIANT's research activities.

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, with the following modification:

Consistent with achieving the goals of this Project, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program.

Applicants should discuss the following:

Availability of biological resources utilized and/or developed (cell lines, reporter systems, vectors, molecules, antibodies, biomarkers, etc.) as appropriate.

Availability of technologies and protocols developed with funds from this award as appropriate and consistent with achieving the goals of the Project.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Discovery and Analysis Project)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Discovery and Analysis Project)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.

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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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

Use of Common Data Elements in NIH-funded Research

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

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

Investigator(s)

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

Specific to the FOA: How well has RADIANT leadership planned scientifically and administratively for the successful oversight of RADIANT, and how well has study leadership demonstrated their commitment and ability to devote adequate time to the effective management and conduct of RADIANT?

Innovation

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

Approach

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

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 the FOA: How well has RADIANT planned procedures for establishing and coordinating activities between relevant RADIANT components to carry out the network's goals? How well does RADIANT plan for successful utilization of resources from other NIH-funded centers in a meaningful way? How efficient and effective is RADIANT's timeline for achieving feasible and realistic goals?

Environment

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

Review Criteria - Administrative Core

Reviewers will consider each of the criteria below in their overall impact score for the Data and Administrative Coordinating Center. Reviewers should NOT provide individual criterion scores for the Administrative Core.

How does the administrative and organizational structure of the Administrative Core support the attainment of RADIANT's goals? What is the level of experience, commitment and leadership ability of the Administrative Core PI(s)/PD(s) and staff, and how will the leadership team adequately manage RADIANT? What plans are in place for coordination, establishment of a strong collaborative environment, and identification and resolution of problems that arise? Describe the management plan for overseeing resources and reviewing progress of key RADIANT committees and programs. How will plans for the composition and functioning of a central IRB for research conducted by RADIANT be feasible and suitable? What sort of plans are in place for the creation of meaningful internal and external collaborations to move RADIANT research efforts forward?

Review Criteria - Database and Repository Core

Reviewers will consider each of the criteria below in their overall impact score for the Database and Repository Core. Reviewers should NOT provide individual criterion scores for the Database and Repository Core.

How well do the RADIANT PIs demonstrate their expertise, commitment, and leadership ability with respect to managing the database and repository? How well do the relevant facilities and resources support database and repository operations? How well developed is the study leadership's plan to submit, harmonize, and integrate data into a searchable data structure, and how well with this yield organized and meaningful data for future research efforts? How well-developed are the plans to assign unique identifiers and utilize them for future plans to merge data/samples? How well will the searchable catalog of open access data encourage and facilitate the use of data within the database by internal and external investigators? How well-developed is the plan to acquire and process biospecimens with respect to yieldig adequate sample viability and integrity for future research? How thorough are the plans to ensure adequate quality control management? How well developed are the plans to share and track the use of data and biospecimens? How well established are the processes and criteria for prioritization and usage of data and samples?

Review Criteria - Discovery and Analysis? Project

Reviewers will consider each of the criteria below in their overall impact score for Discovery and Analysis Project. Reviewers should NOT provide individual criterion scores for Discovery and Analysis Project.How extensive are the study team expertise, commitment and leadership abilities to enable successful implementation of the proposed Discovery and Analysis activities? How well will the plans for continuing outreach and identification of rare/atypical forms of diabetes yield sufficient numbers of individuals/families for research? How well thought out are the plans to determine which individuals/families will be chosen for further in-depth study capture the relevant study population and include all important individuals for study? How thorough is the plan for the study of individuals/families with rare/atypical forms of diabetes feasible, and how well-developed are the resources and services for studying these individuals? How well does the plan allow for the proposed collection of common demographic, phenotypic, and genetic information in order to result in meaningful research findings? How thorough is the plan to ensure compatibility and comparability of data collected for future research, and is it sufficient? How significant are the planned Discovery and Analysis activities and will they contribute to the goals of RADIANT?

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

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

Specific to this FOA: How well did the study group do during the initial grant cycle with respect to meeting recruitment milestones? How well did RADIANT do during the first grant cycle in terms of advancing sufficient numbers of participants from Stage 1, screening evaluation for possible cases of atypical diabetes, to Stage 2, whole genome sequencing, and Stage 3, deep phenotyping?

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

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

Following initial peer review, recommended applications will receive a second level of review by the National Diabetes & Digestive & 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: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

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

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

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

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

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

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

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

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

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

1. Developing the research design and study protocol, including definition of objectives and approaches, sample size and power calculations, and establishing procedures for participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.

2. Establishing a Steering Committee to implement, coordinate and manage the project(s). Recipient(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Recipients will be required to accept and implement the common protocol(s) and procedures approved by the Steering Committee.

3. Designating Protocol Chairs. The Program Directors/Principal Investigators (for studies involving multiple protocols) shall designate a single Protocol Chairperson (if the Program Director/Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.

4. Implementing collection of data specified by the study protocol. For a multi-center study, each recipient/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.

5. Establishing procedures for data quality and completeness. Recipients are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple sites, a plan for analysis of pooled data will be developed by the Steering Committee.

6. Submitting interim progress reports, when requested or agreed upon by both parties, to the NIDDK Program Official including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Official may require additional information from individual recipients/sites. Such reports are in addition to the required annual noncompeting continuation progress report.

7. Reporting of the study findings. Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. The awardee must also be adherent to Study Publication and Presentation Policy. The NIDDK will have access to and may periodically review all data generated under an award. NIDDK staff may co-author publications of findings with awardees consistent with NIH and study policies.

8. Any third-party (including industry, academia, and foundations) collaboration should be governed by a research collaboration agreement (e.g. Clinical Trial Agreement, Research Collaborative Agreement, etc.) or any third-party contract mechanism(s) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network studies between grantee and third-party will be provided to the NIDDK Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network policies. Further, at the request of the NIDDK Program staff, any other network-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions , and Section 8.5.2, titled: Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support , noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.

9. Any involvement of a third-party (including industry, academia, and foundations) in the study and network activities that includes access to any network study data and biosamples, or study results that are not publicly available, or using the name of the network or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.

10. Study investigators are required to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and steering committee policies on publications.

11. Maintaining confidentiality of information: The awardee(s) will maintain the confidentiality of the information developed by the investigators (i.e., protocols, data analysis, conclusions, etc.) as well as proprietary information of an individual company or other entity collaborating with the study. Any exception requires written approval from NIDDK Program staff.

12. ?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 an NIDDK approved repository per the NIDDK approved sharing plan. The NIDDK has established a Central Repository to support the receipt, storage, and distribution of data, biosamples, and other resources generated in clinical studies funded by the NIH/NIDDK. When the NIDDK Central Repository is to be utilized, prior to enrolling participants, the PI or his/her designee will coordinate with the NIDDK Program and Central Repository staff to prepare for eventual archiving and distribution of the study generated resources that are to be maintained in the Central Repository. All resources transferred to the Central Repository will be under the custodianship of the NIDDK. The study’s leadership will have proprietary control of and exclusive access to the resources per the NIDDK approved sharing plan. Subsequently, these resources will be available to the wider scientific community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/, and https://grants.nih.gov/policy/sharing.htm, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm), as well as the NIDDK policy for resource sharing, NIDDK Data Sharing Policy.

13. Study investigators are required to comply with NIH Policy on the Dissemination of NIH Funded Clinical Trial Information as stated at https://grants.nih.gov/policy/clinicaltrials/reporting/understanding/nih-policy.htm. Per policy, the awardee is responsible for meeting the expectations of this policy. Refer to additional information at https://grants.nih.gov/policy/clinical-trials/reporting/index.htm.

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

An NIDDK Project Scientist with substantial involvement will:

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 awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Project Coordinator, who will provide direct technical assistance to the recipients to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or Project Coordinator 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 awardees 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 insure 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) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.

4. Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.

5. Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high-risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Areas of Joint Responsibility include:

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

Steering Committee

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

The Steering Committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-investigators 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 NIDDK Project Scientist will only have one vote on the Steering Committee, and other NIDDK Program Officials will participate in a non-voting capacity. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.

The Steering Committee Chairperson (someone other than the NIDDK Project Scientist) will provide leadership to the Committee by conducting the Steering Committee meetings and by interacting closely with the recipients during protocol development and implementation.

Dispute Resolution

Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIDDK may be brought to dispute resolution. A dispute resolution panel will be composed of three members --one selected by the awardee (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIDDK, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR 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.

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 75.113and 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 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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

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

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

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

Ellen Leschek, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases? (NIDDK)
Telephone: 301-402-8291
Email: [email protected]

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

Jill Bradshaw
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-1230
Email: [email protected]

Section VIII. Other Information

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

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