Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This NOFO invites applications for Clinical Centers (CCs) to collaborate with a Biostatistics Research Center (BRC) to develop and implement an observational study to better understand the neurocognitive impact of new onset type 1 diabetes (T1D) in pre-pubertal children. The overarching goals of the clinical consortium are to establish a diverse longitudinal cohort of pediatric patients newly diagnosed with T1D that will allow investigators to: 1) better understand the impact of T1D on the developing brain, including neurocognitive and psychosocial functioning ; 2) identify and evaluate potential risk and protective factors associated with T1D-related neurocognitive impact, including magnitude and duration of blood glucose time in range (TIR), time spent in hypoglycemia or hyperglycemia and other continuous glucose monitoring (CGM) metrics, and diabetic ketoacidosis (DKA) status at diagnosis; and 3) assess potential associations between use of newer and emerging diabetes management technologies (e.g., automated diabetes management systems) and neurocognitive functioning among children with T1D. All recipients selected to participate must agree to be part of a consortium that will collaboratively develop and implement a uniform protocol.

Background

There is growing evidence of neurocognitive complications of T1D, with approximately 28% of middle-aged adults with T1D and 48% of older adults with T1D meeting criteria for clinically significant cognitive impairment (defined as performance ? 1.5 standard deviations below normative data on ? 2 cognitive tests). Early age of onset of T1D, longer disease duration, greater frequency and severity of hyperglycemia and hypoglycemia, hypoglycemia unawareness, DKA, and clinical severity at the time of diagnosis may increase risk for impairments in neurocognitive function. However, age-related changes and vascular complications associated with T1D in adults make isolating mechanisms associated with neurocognitive perturbations more complex. Clinical targets also may be less modifiable as persons with T1D advance in age and disease burden increases. Research in modern cohorts of pediatric patients with T1D earlier in the developmental spectrum and prior to the development of complex disease (e.g., moderate to severe complications of T1D, cardiovascular disease, dementia) can inform mechanisms, critical periods for prevention and intervention, and strategies to mitigate the risk of neurocognitive complications of T1D in later life.

Early childhood development is characterized by marked changes in brain structure and function at a time when the brain may be especially vulnerable to dysglycemia and other metabolic conditions associated with T1D. There are limited data from adequately powered longitudinal studies on the brain and neuropsychological function, especially in contemporary and diverse cohorts with pediatric participants with T1D, and existing longitudinal studies with neuropsychological and neuroimaging data have shown mixed results. Further, there have been significant advances in diabetes management technologies in recent years and increases in time in optimal glycemic range may be protective against neurocognitive complications, but this has not been adequately explored. In addition, the functional impact of neurocognitive changes experienced after a T1D diagnosis has not been adequately explored in prospective studies. Thus, current knowledge of how clinical features of T1D (e.g., age of onset, disease duration, glycemic variability and control, time course of dysglycemia, diabetes management regimens, frequency and severity of hypoglycemic episodes, DKA) may lead to changes in brain structure and function and the resulting impact on the clinical course of T1D, disease management, and other important outcomes (e.g., academic performance) is limited. Recent advances in neuroimaging, computerized cognitive assessment, and automated diabetes management systems (e.g., CGM, artificial pancreas technologies) provide researchers with a unique opportunity to improve the characterization of both neurocognitive and clinical aspects of pediatric T1D, and identify critical risk or protective factors (e.g., role of DKA, premorbid neurocognition, cognitive reserve, key developmental periods, effects of treatment regimen) for common neurocognitive complications. Furthermore, the identification of risk and/or protective factors for differential neurocognitive outcomes in T1D could lead to the development of treatment protocols aimed at preventing or limiting neurocognitive complications. Information gleaned on the neurocognitive consequences of glycemic control approaches and outcomes may also inform algorithms for future automated diabetes management systems. If successful, this observational cohort study is expected to inform future clinical and research applications to decrease adverse neurodevelopmental outcomes and long-term neurocognitive sequelae of T1D.

Scope

This NOFO invites applications from CCs to propose a clinical study with the overall goal of evaluating neurocognitive functioning in pre-pubertal children newly diagnosed with T1D as well as potential risk and protective factors. It is expected that the study will recruit and evaluate a diverse cohort of pediatric patients newly diagnosed with T1D as well as a comparison group. A separate NOFO (RFA-DK-23-009) will solicit applications for a Biostatistics Research Center (BRC) to provide additional scientific input as well as coordinate study design, protocol development and implementation, and data analysis.

Although the ultimate design of the study will be finalized by the Steering Committee, it is anticipated that each study participant will undergo neuroimaging, cognitive and neuropsychological assessment, and clinical evaluation. Therefore, applicants to this NOFO are required to understand these assessment tools and related variables (e.g., neurocognitive function, imaging biomarkers, glycemic indicators), which will be used to generate primary and secondary outcomes. It is expected that state-of-the-art cognitive assessments, such as the NIH Toolbox, will be utilized to assess global cognitive functioning and multiple facets of cognition over time; further, the neuroimaging protocol should be designed to evaluate both structural and functional impairments.

Applications also should address internalizing (i.e., anxiety, depression) and externalizing symptoms in children and mood in parents and consider these confounding variables in the context of the study. The CCs must recruit pre-pubertal children newly diagnosed with T1D and reflect the racial, ethnic, and socioeconomic diversity of the US and, in particular, children with T1D. Diversity in recruitment is especially important in light of recent evidence that T1D is increasing at higher rates among young people from racial and ethnic minority groups than among non-Hispanic white youth. NIDDK places a high priority on clinical studies to understand and eliminate health disparities and promote health equity. Applications must incorporate assessments related to social determinants of health. Investigators are encouraged to review the NIH Common Data Elements (CDEs) to ensure that selected measures are applicable across studies. To facilitate establishing CDEs, applicants are strongly encouraged to consider use of the PhenX Social Determinants of Health (SDOH) Assessments Collection (https://www.nihmd.nih.gov/programs/collab/phenx/).

It is anticipated that the proposed study will require a sample size larger than can be provided at one site. The applicant should describe a study to be conducted under a common protocol by the consortium, including the sample size required for the full study, as well as the number of participants to be recruited at the applicant's site. The proposed research study will enable reviewers to evaluate the applicant's ability to identify the critical issues to be addressed in the study and rigorously design such a study. Peer review will consider both the scientific merit of the application as well as the ability to recruit and conduct the study. The recipients , including PD(s)/PI(s) at the BRC and CCs, will assemble to form a Steering Committee (see below), which will meet to develop a common protocol and manual(s) of procedures. The submitted applications will serve as a starting point for the Steering Committee's deliberations. It is expected that the Steering Committee will meet annually in the Washington, DC area over the course of the study and have frequent contact via videoconferencing during the planning phase, which is expected to take twelve months.

NIDDK is committed to conducting clinical studies that are developed and implemented with active stakeholder engagement. Active stakeholder engagement entails meaningful involvement of persons with lived experience with T1D, caregivers, family members, clinicians, healthcare systems, advocacy groups, and other relevant stakeholders in the development, design, and execution of the study. Stakeholder engagement must involve bidirectional communication and interactions that result in informed decision-making about high-priority research needs and issues that are important to stakeholder/community members. Stakeholder engagement is expected to help shape the design of the study, as well as recruitment and retention approaches, especially for populations that may be underrepresented in pediatric T1D research, including individuals from racial and ethnic minority groups, rural populations, and socioeconomically disadvantaged and medically underserved communities.

Consortium Organization

1. Clinical Centers

Clinical Centers (CCs) will recruit pre-pubertal children with T1D and an appropriate comparison group in which potential confounders that would impact cognitive function are accounted for. The population recruited should be racially and ethnically diverse. It is expected that the overall population recruited by the entire consortium will reflect, at minimum, the demographic distribution of the U.S. population of children with T1D; CCs are encouraged to oversample populations of children with T1D underrepresented in prior research.

The PD(s)/PI(s) and key co-investigators at each CC and the BRC will be expected to collaborate in designing and implementing the uniform study protocol. CCs must not only demonstrate that they have access to the requisite number of patients but also proven experience in recruiting and retaining youth with T1D from diverse racial and ethnic backgrounds as well as experience in clinical care for newly diagnosed youth with T1D. CCs must also have expertise in neuroimaging procedures and utilizing new and emerging diabetes technologies. It is expected that assessment measures will include CGM, and CCs should have resources for diabetes technology education. The CCs will collect data in accordance with established study procedures and submit all samples and data to the BRC, central laboratory, and additional cores, as appropriate and required by the protocol. Investigators at the CCs will conduct analyses in conjunction with the BRC. Key personnel from the CCs will be required to attend an annual meeting of consortia investigators.

It is expected that the CCs will actively engage stakeholders from study onset, including consulting with local stakeholders prior to application submission and working with the BRC to form a central stakeholder advisory board at the start of the study, with continued local stakeholder engagement for the duration of the award period.

2. Biostatistics Research Center (BRC)

There will be a single BRC, which will have scientific as well as coordination responsibilities. The BRC will provide the organizational framework for the management, direction, and overall coordination of the national multi-site consortium, including but not limited to: study performance, dissemination of plans and policies across CCs, and data harmonization, integration and analysis, in support of the study objectives and research questions described above. BRC investigators will work with the CC investigators to develop the scientific design of the study and have primary responsibility for ensuring that the design of the study, including the primary outcome, is scientifically sound and supported by appropriate power calculations. The BRC will provide biostatistical and analytic expertise and conduct analysis and interpretation of all study data in conjunction with investigators at the CCs. The BRC will be responsible for guiding development of the statistical analysis plan for the study as a whole and for each manuscript reporting pre-specified primary and secondary outcomes.

The BRC will coordinate the development of a core study protocol; evaluation of progress and results; recommendation of study changes, if necessary; and suggestions regarding future directions. It is expected that the BRC will oversee the creation and management of key study cores (e.g., central processing laboratory, neuroimaging core), as needed, to meet study objectives. The BRC may need to establish scientific collaborations for specialized outcomes.

The BRC will coordinate the interactions among the individual CCs, including standardization of protocols, training of staff, and reliability testing for any neurocognitive, clinical, and/or other phenotypic assessment proposed to ensure administration of these measures is consistent across research sites. The BRC also will ensure standardization of CGM devices and data collection; acquisition of clinical, cognitive, neuropsychological, and neuroimaging data; study protocols; and data analysis pipelines. The BRC is also responsible for the collection, management, and analysis of all clinical and laboratory data, including establishment of central laboratories and cores as needed. The BRC will coordinate the movement of biologic samples from the CCs to the central laboratory and, subsequently, to the NIDDK Central Repository, where samples will be stored for future analysis. The BRC will similarly coordinate with the CCs to ensure the flow of collected data to the appropriate central reading center or informatics lead. The BRC will also coordinate with the NIDDK Central Repository or other NIDDK-approved repositories as appropriate to prepare all study data for eventual archiving, access, and distribution.

The BRC will be responsible for ensuring participant confidentiality and safety, and quality control. The BRC will conduct training and certification of study staff and maintain and update the manual of operations. The BRC will oversee implementation of and adherence to the study protocol including training of research coordinators. The BRC will coordinate communication among and with the CCs. The BRC will also be responsible for establishing and managing activities related to the single IRB. In addition, the BRC will develop procedures to require study investigators and other relevant personnel associated with the study to identify and manage financial and other conflicts of interest at least annually and share this information with NIDDK staff.

If additional sites are needed to recruit adequate numbers of participants (both pre-pubertal children with T1D and a comparison group), subcontracts may be added to individual study sites or the BRC. The BRC will be responsible for recruitment of additional sites.

This study will have an NIDDK-appointed Observational Safety Monitoring Board (OSMB). The BRC will prepare appropriately detailed reports for the Steering Committee, the OSMB, and NIDDK staff at regular intervals. The BRC will be responsible for the planning and logistics of meetings of the Steering Committee and its subcommittees, including an annual in-person meeting of consortia investigators, and will assist NIDDK with the logistics for OSMB meetings. The BRC will also oversee the creation of a central stakeholder advisory board, comprised of representatives from each CC, with the expectation that stakeholders will be active participants in the Steering Committee and contribute to the study design and execution.

To support the consortium, the BRC will identify fixed and variable costs, establish procedures for negotiation of third-party agreements and selection of subcontractors (i.e., supplies, clinical sites, clinical/research laboratories, biospecimen repositories, etc.), and develop processes to efficiently administer and manage these entities throughout the project.

The NIDDK Technology Advancement Office must be consulted early in the process when an NIDDK-funded study enters into a collaboration agreement. These consults will be facilitated by the NIDDK Program Official. Applicants should also refer to NIDDK's Policies for Clinical Researchers to set the expectation for BRC roles and responsibilities.

3. Steering Committee

The primary governing body of the study will be the Steering Committee, comprised of the PDs/PIs of the BRC and each CC, a representative from the central stakeholder advisory board, and the NIDDK Project Scientist. The Steering Committee will develop policies and procedures for the study group and ensure that these policies are properly implemented. These may include procedures for modification of study design, use of study samples and data, approval of ancillary studies, publication and presentation of study findings, monitoring study progress, determining completeness and quality of data collection, and other performance measures. NIDDK expects the investigators to develop robust ancillary study policies to provide opportunities for outside investigators to leverage collected data and biospecimens, as well as the recruited cohort, to expand the scientific output of the group.

4. Project Scientist

The NIDDK Project Scientist will assist the Steering Committee in designing and carrying out the study. The Project Scientist will provide scientific support to recipients' activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications, and overall performance monitoring.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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

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

Foreign components, as defined in the NIH Grants Policy Statement, are not 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 registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

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

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments:

Consortium Assurance: The filename "Consortium Assurance.pdf" should be used.

The PD(s)/PI(s) should provide a letter stating his/her willingness to participate in Consortium activities, including sharing the scientific portion of the application, participating in meetings at the NIH and regular conference calls and abiding by approved Consortium policies, and following the common protocol agreed to during the planning phase. In the letter, the PD(s)/PI(s) should also discuss past experiences participating in multi-center studies.

In addition, the PD(s)/PI(s) and an authorized Institutional Official should provide evidence that the Institution is willing to sign a standard reliance agreement and use the single IRB proposed by the BRC as part of its application, in accordance with NIH policy on the use of a single Institutional Review Board for multi-site research,?https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-076.html, and federal regulation for cooperative research (45 CFR 46.114).

Applications that lack the Consortium Assurance letter are considered incomplete and will not be peer reviewed.

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

Applicants are required to provide detailed interim performance measures and timelines for completing key objectives and administrative functions for the proposed clinical study, as applicable. Milestones should be easily measurable and realistic. Milestones may include, as applicable, but are not limited to:

• Finalization of the clinical study protocol and informed consent/assent forms (with program director agreement, if applicable) and establishment of a single IRB and provision of IRB approval
• Contracts/third party agreements
• Training of study staff
• Anticipated date of enrollment of the first participant
• Enrollment of 25%, 50%, 75% and 100% of the target sample size
• Follow-up visit completion, if applicable, of 25%, 50%, 75% and 100% of the enrolled study population, including women, minorities and individuals across the lifespan
• Expected drop-out or lost-to-follow-up rate
• Completion of data collection
• Completion of primary endpoint and secondary endpoint data analyses
• Completion of final study report and manuscript submission
• Closeout plans/communication of results to participants

These milestones will be negotiated at the time of the award, as appropriate. Future year support is contingent on satisfactory achievement of performance milestones. If milestones are not achieved fully, NIDDK may request development of a remedial plan and more frequent monitoring of progress, or take other remedial actions.

The Milestone plan is a separate document from the Study Timeline. Applications that lack the Milestone Plan are considered incomplete and will not be peer reviewed.

Stakeholder Engagement Plan: The Filename "Stakeholder Engagement Plan.pdf" should be used.

Applicants are required to provide a Stakeholder Engagement Plan. NIDDK is committed to conducting clinical studies that have been developed with meaningful stakeholder engagement. Meaningful stakeholder engagement entails active and relevant involvement of patients, caregivers, family members, clinicians, healthcare systems, advocacy groups, and other relevant stakeholders in the development, design and execution of the study.

Stakeholder engagement approaches may reflect stakeholder involvement along the continuum of community engaged research.

Stakeholder engagement should identify high-priority research needs and issues that are important to stakeholder/community members.

It is expected that, since a proposed study design must be included in the U01 application, applicants will propose appropriate stakeholder engagement which may be initiated during the first planning year of the trial.

The application should also describe any stakeholder engagement efforts planned during the U01 period and how these activities will be used.

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

The annual budget requested should match the timeline proposed for the project and the scope of the project. Applicants may assume that the cost of supplies related to cognitive and neuropsychological evaluation, CGM, and laboratory assays will be covered in the budget of the BRC, via the chosen assessment methods and central laboratory. CCs will be responsible for costs associated with local conduct of the study, such as: neuroimaging assessments, consortium-related meeting travel, local facility fees, participant reimbursement, recruitment activities, and other site-specific operating costs, as needed. Although the sample size calculation provided in the Research Strategy should reflect the total number of participants required across all sites, each applicant should provide a budget that reflects the number of participants that can be realistically recruited at his/her own site (including any subcontracts if auxiliary recruitment sites under the direction of the applicant are proposed). The first 12 months will be devoted to planning; the budget during the first year will cover PD(s)/PI(s) and critical co-investigator effort in protocol development, travel to annual consortium meetings, local travel for stakeholder engagement, local stakeholder engagement activities, and initial hiring of new staff. After the planning period, the budget should cover all study activities for the study sample proposed in the application (based on the number of participants projected to be recruited at the applicant’s CC). It is anticipated that CC sites will need to hire and train staff (on local operations) in advance of the actual initiation of recruitment. The study should be completed before the end of year 5 to allow ample time for data clean-up and analysis. It should be understood that, in the event of an award, the budgets at the CCs will be adjusted from that proposed in the application to reflect the actual needs of the consortium-developed core protocol and the expertise needed on the Steering Committee. In addition, budgets may be adjusted during the out-years of the study based on recruitment success. Once the study starts, it is anticipated that there will be at least one in-person consortium meeting in the Washington DC area per year.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

The applicant must clearly articulate the significance of the proposed study, including why the clinical study is needed, what evidence gap the study will address, and how results will impact clinical care and/or public health. The applicants must clearly describe the study team’s collective experience with conducting state-of-the-art neurocognitive assessments, including neuroimaging, and her/his/their ability to recruit the proposed patient population of pre-pubertal children newly diagnosed with T1D and a comparison population, without duplicating information in the biosketches.

The application must include a detailed description for the study design, addressing the scientific rationale for the design chosen, the outcomes being assessed, and the populations to be studied, including an appropriate comparison population which accounts for confounders that might impact neurocognitive function. Applications must also incorporate assessments related to social determinants of health. The discussion should include:

• A longitudinal design to prospectively examine the neurocognitive complications of T1D, role of dysglycemia, and potential risk and protective factors from disease onset into late childhood;
• A design with a sample size that is sufficiently large to achieve the study goals, accounting for attrition (e.g., loss to follow-up, withdrawal);
• The inclusion of a sufficiently powered comparison group, matched to the demographic characteristics of the proposed cohort of pre-pubertal children with T1D, while also accounting for potential confounders that might influence cognitive functioning;
• A sampling strategy designed to establish a sample that is broadly representative of and generalizable to the U.S. population with T1D, including males and females, as well as major racial, ethnic, and sociodemographic subgroups of the population; it is recognized that the level of precision achieved for various subgroups may vary, and that probability-based sampling and oversampling of certain demographic subgroups or geographical regions may be required;
• Cognitive and neuropsychological batteries that allow for the assessment of major cognitive dimensions associated with T1D-related dysfunction (e.g., tests of intelligence, sustained attention, visuospatial skills, psychomotor speed, executive functions);
• Descriptions of developmentally appropriate neurocognitive (including cognitive and neuropsychological assessment and neuroimaging), clinical, laboratory, and psychosocial/behavioral measures that will be collected to enable the research questions to be answered. Please provide a table showing the timepoints at which each measure will be collected.
• Standardized measures and protocols that, where possible, are compatible with data-harmonization efforts (e.g., PhenX Toolkit, NIH Toolbox), ongoing studies of T1D, and other large-scale studies to maximize data compatibility.

Preliminary data addressing the need for and supporting feasibility of the study must be discussed. The discussion of supporting data that provide the basis for the study's design must address the adequacy and quality of previous studies.

Letters of Support: Letters of support should be provided from all participating clinics and/or hospitals, as well as collaborators at other sites.

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.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

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

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Please include a discussion of the availability of potential participants for the proposed study (both pre-pubertal children newly diagnosed with T1D and a comparison group) any key inclusion and exclusion criteria, and anticipated yield from recruitment and screening efforts.

The plan should also include a discussion of past experiences in recruiting and retaining similar populations, expected challenges to recruitment and retention, and possible contingency plans.

Section 3 - Protection and Monitoring Plans

All parts of Section 3 are required under this NOFO.

3.3 Data and Safety Monitoring Plan

In addition to the description of safety monitoring, address plans to monitor study performance, including plans to assure fidelity to the protocol and integrity of the data. Information about Data and Safety Monitoring Plans in available on the NIDDK website: ?https://www.niddk.nih.gov/research-funding/human-subjects-research/policies-clinical-researchers/data-safety-monitoring-plans.

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Use of Common Data Elements in NIH-funded Research

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

Post Submission Materials

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

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The project proposed in the application may not be the final study conducted in the actual longitudinal study. However the planned study will enable reviewers to evaluate the applicant's ability to identify critical scientific questions, rigorously design a study, recruit study participants, and conduct the study.

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

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

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

Stakeholder Engagement

How appropriate is the description of stakeholder engagement in the development of the proposed study that reflects meaningful interaction with relevant stakeholders, including a discussion of how information from meetings with stakeholders was used and how bidirectional communication occurred?

Clinical Milestones

How reasonable are the proposed clinical milestones for the conduct of the proposed study?

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

2. Review and Selection Process

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

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

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the NIDDK National 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.
• Compliance with data management and sharing policies.

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

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

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

2. Administrative and National Policy Requirements

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

• 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 NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies. The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the 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 recipients and the NIH as defined below.

The Program Director(s)/Principal Investigator(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, completeness, and security. 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 recipient 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 recipients consistent with NIH and study policies.

8. Any third-party collaboration (including but not limited to interactions with organizations from industry, academia, and nonprofit institutions) should be governed by a research collaboration agreement (e.g., Clinical Trial Agreement, Research Collaborative Agreement, etc.) or any third-party contract mechanism(s) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network studies between grantee and third-party will be provided to the NIDDK Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network policies. Further, at the request of the NIDDK Program staff, any other network-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions , and Section 8.5.2, titled: Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support , noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.

9. Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and network activities that includes access to any network generated resources (i.e., data and bio-samples), 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. Maintaining confidentiality of information: The recipient(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.

11. Data Management and Sharing Plan: In accordance with the NIH Policy for Data Management and Sharing (NIH NOT-OD-21-013), the NIDDK approved plan will become a term and condition of award, be routinely monitored during the award period, and compliance may factor into future funding decisions. By the end of the funding or proprietary period, a recipient or study group may not continue to use or share study generated resources until those resources are available to the public via a NIDDK approved repository per the NIDDK approved plan. The NIDDK has established a Central Repository to support the receipt, storage, and distribution of data, bio-samples, 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. These resources will be available to the wider scientific community in accordance with the NIH Data Management and Sharing policy (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), per the NIDDK approved data management and sharing plan.

12. Study investigators are required to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols, steering committee policies on publications, and the NIDDK approved Data Management and Sharing Plan .

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/clinical-trials/reporting/understanding/nih-policy.htm. Per policy, the recipient 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 recipient 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 recipients by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.

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

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

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

1. Interact with the Program Director(s)/Principal Investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the Program Director/Principal Investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.

2. Review and approve protocols prior to implementation to 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 Recipients 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 recipients, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official, and will provide periodic supplementary reports upon request.

The Steering Committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-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 frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee. The NIDDK Program Official may serve as a non-voting member on the SC.

A Chairperson of the Steering Committee will be selected and voted on by the Steering Committee members. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings and by interacting closely with the recipients during protocol development and implementation. The NIDDK Project Scientist may not serve as Chairperson. The NIDDK Program Official should be consulted regarding the selection of the Chairperson to provide any feedback regarding concerns regarding potential for bias or conflict of interest or lack of required expertise.

External Consultants

An independent panel of External Consultants may be established by the Steering Committee. The External Experts will review periodically interim progress of the UXXs and report to the Steering Committee members. Members of the panel of External Experts may be asked, on an ad hoc basis, to participate in the peer review of applications for new research initiatives that utilize special opportunity pool funds.

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

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

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

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

Section VII. Agency Contacts

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

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]

Maureen Monaghan Center, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-3269
Email: [email protected]

Theresa Teslovich Woo, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-1871
Email: [email protected]

Michele L. Barnard, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8898
Email: [email protected]

Christina Coriz
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8848
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.
This FOA is supported under the authority of P.L. 116-260, Consolidated Appropriations Act, 2021; Section 302. "Diabetes Programs .