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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose and Research Objectives

The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health of the U.S. Department of Health and Human Services is seeking applications for the Type 1 Diabetes TrialNet Coordinating Center (TNCC).

NOTE: Applicants to this TNCC opportunity should read the companion Notice of Funding Opportunity (NOFO) for the TrialNet Clinical Network Hub (HUB) to understand how these funded units work together. Applicants are strongly encouraged to contact the NIH Program Official listed below before preparing an application. In addition, NIH staff will lead webinars as needed for applicants to answer questions about this opportunity and TrialNet.

Background

TrialNet was established to provide a highly collaborative clinical trials network to develop and implement trials aimed at preventing type 1 diabetes (T1D) and halting T1D disease progression by preserving insulin production before and after diagnosis. Since T1D is relatively rare (only 5-10% of people with diabetes have type 1), a large network is needed to identify participants and implement trials for prevention. In addition, progression from risk identification to symptoms can take years, so TrialNet prevention trials are typically of long duration. These challenges justify an ongoing, large, highly collaborative clinical trials network.

The TrialNet partnership currently consists of a TrialNet Clinical Network Hub ("HUB") (funded by NIDDK cooperative agreement), a TrialNet Coordinating Center ("TNCC") (funded by NIDDK cooperative agreement), 17 North American Clinical Centers (funded by TNCC subcontracts), a TrialNet Chair Office (funded by TNCC subcontract) and the NIDDK. The HUB provides the network with leadership in the coordination of communications for screening, recruitment and trial implementation across the network and within the broader T1D community. This coordination increases the operational efficiency and productivity of the TrialNet network. The TNCC provides the network with scientific leadership in study design and monitoring and oversees data and sample collection, data processing, biostatistical analyses and administrative operations. In addition, the TNCC selects the North American TrialNet Clinical Centers. The TrialNet Chair office includes a Chair and Vice Chair. They provide scientific and medical leadership to the network’s Steering Committee (SC), oversee protocol/consent/volunteer handbook development, and manage the receipt and review of proposals for future TrialNet studies. The NIDDK Project Scientist assists the SC in carrying out all TrialNet studies and provides scientific support to awardee activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications and overall performance monitoring. The TrialNet Clinical Centers are funded to implement trials, help in the design and selection of new trials, and serve on operational committees across the network. In addition, TrialNet has numerous affiliates, with >100 locations worldwide. The TrialNet network is supported by approximately 20 central laboratories and support units (all TNCC subcontractors).

TrialNet's findings, together with those of others, led to the establishment of a model describing three distinct stages of T1D. This model of T1D development has been endorsed by the JDRF, ADA and Endocrine Society. The first two stages of T1D, identifiable by TrialNet screening prior to onset of T1D symptoms, are Stage 1: >2 different positive diabetes-related autoantibodies, and Stage 2: >2 different positive diabetes-related autoantibodies plus impaired glucose tolerance. Stage 3 is reached when there is a clinical diagnosis of T1D. Identifying T1D in its earliest stages allows for prompt intervention and the potential to alter the disease course. TrialNet's goal is to find ways to stop T1D progression by testing disease-modifying interventions that preserve ß-cell production.

To achieve this goal, TrialNet performs trials of interventions to preserve insulin production before (prevention trials) and after (new-onset trials) symptom onset. Data show that preservation of insulin production after onset can improve glucose control and reduce complications. TrialNet’s work to prevent T1D benefits from TrialNet's new-onset trials. Family members of participants in new-onset T1D treatment trials are often interested in being screened for T1D risk and participating in prevention trials. In addition, TrialNet data and samples from clinical studies as well as TrialNet mechanistic studies generate information to improve understanding of the pathophysiology of T1D. Better understanding of the mechanisms of T1D could lead to targeted treatments demonstrating increased efficacy. TrialNet recently launched a new trial supported by mechanistic data from its prior trials. Mechanistic studies could also identify biomarkers to serve as intermediate study endpoints to enable intervention earlier in the disease process as well as decrease trial duration and sample size. Mechanistic studies are accomplished directly by the network, by separately funded ancillary studies involving TrialNet participants, or by collaborations with independent investigators and/or consortia with complementary goals. TrialNet’s former and current studies and trials are listed in the table below:

*Study uses a maximum information design so there is not an exact enrollment target. Enrollment will be complete when the necessary number of events occurs.

**Trial performed jointly with DirecNet at TrialNet Centers.

***Immune Tolerance Network (ITN) studies reviewed and approved by TrialNet and conducted at TrialNet Centers include: 1) Treatment of Recent Onset T1D with AntiCD3 Monoclonal Antibody; 2) Thymoglobulin for New Onset T1D; 3) A Phase I Trial of Proleukin and Rapamune in Recent Onset T1D; and 4) Treatment of Recent Onset T1D with Anti-IL6R (Tocilizumab)

Summary of TrialNet Governance

Clinical Center PDs/PIs serve as members of the TrialNet SC and as a group comprise the majority of the SC. SC voting members include the Clinical Center PDs/PIs, the TNCC PD/PI, the HUB PD/PI, the SC Chair and Vice Chair, and the NIDDK Project Scientist. New for the upcoming funding period, one representative from the community impacted by the disease (individuals with T1D, family members and friends of individuals with T1D) and one representative from T1D non-profit groups (JDRF, ADA, Children With Diabetes, etc.) will be included as voting members of the SC. If the HUB PD/PI, Chair and Vice Chair are also PDs/PIs of a Clinical Center, they will have only one SC vote. TrialNet also has a Collaborative Mechanistic Studies Panel (CMSP), a group of T1D and immunology experts (including Clinical Center PDs/PIs and external consultants) who interact with the research community to provide guidance on TrialNet mechanistic studies and enhance biomarker discovery in the context of TrialNet's mission. Representatives from the CMSP also serve on the SC. The SC uses a stepwise voting process to decide which trials and studies to perform.

The NIDDK Technology Advancement Office negotiates collaborative agreements between NIDDK, the TNCC and industry/non-profit/academic partners. TrialNet’s regulatory sponsor is NIDDK, and the NIDDK Regulatory Specialist communicates with the FDA when a protocol may be required to operate under an IND/IDE. These activities are facilitated by the NIDDK Program Officials.

TrialNet Organization

1. TrialNet Coordinating Center (THIS NOFO)

The TrialNet Coordinating Center (TNCC) provides the network with scientific leadership in study design and monitoring, and oversees data processing, biostatistical analyses and administrative operations. The TNCC oversees the screening of relatives of individuals with T1D for monitoring and possible inclusion in intervention studies aimed at preservation of insulin-producing cells. The TNCC is responsible for the design, conduct and continuation of intervention studies in individuals at early pre-clinical stages of T1D and in individuals with new-onset T1D (as selected by the TrialNet Steering Committee). The TNCC will: (1) support a wide range of research projects in varying stages of development, implementation and completion, and (2) provide data and sample management, including standardized acquisition, quality control, dissemination, and public accessibility. The TNCC will conduct a competition to select 10-20 North American TrialNet Clinical Centers, which will be funded via TNCC subcontracts. Details on the TNCC, which is being competed with this NOFO, are provided below.

2. TrialNet Clinical Centers

The TrialNet Clinical Centers are responsible for screening relatives of individuals with T1D, enrolling those who are at-risk for disease into the Pathway to Prevention monitoring study, and recruiting eligible, interested subjects into TrialNet prevention and new-onset studies. TrialNet Clinical Centers enroll, treat and retain TrialNet prevention and new-onset study participants. Some TrialNet Clinical Centers support TrialNet Affiliate Sites. Clinical Centers regularly interact with the TNCC, the HUB, the NIDDK and its partners.

3. TrialNet Chair and Vice Chair
 
The TrialNet Chair and Vice Chair will be selected by the SC and approved by the NIDDK. The Chair and Vice Chair will be chosen from the pool of Clinical Center directors. The Chair functions as the scientific coordinator for network trials and provides leadership to the SC by conducting SC meetings, representing the study group to the Data and Safety Monitoring Board (DSMB) and External Evaluation Panel (EEP) and by interacting closely with members of the SC during protocol development and implementation. The SC Vice Chair assists the Chair with these functions. Each TrialNet Chair and Vice Chair term is five years, but the term may be renewed. See the Terms and Conditions of the award for more details about the Chair selection process.

4. TrialNet Clinical Network Hub (HUB) 
 
Open competition for continued support of the TrialNet HUB is being conducted concurrently with this open competition for continued support of the TNCC. The HUB is responsible for developing and leading a coordinated program to enhance risk screening, recruitment, conduct and retention for TrialNet’s prevention and new-onset trials.

During the analysis and publication phase of TrialNet studies, the HUB is responsible for working with the TNCC and network investigators on the publication of manuscripts.

The HUB PD/PI participates on the TrialNet Executive Committee and is a member of other network working groups. The HUB works closely with the TNCC, Clinical Centers, Chair Office and NIDDK Project Scientist in a collaborative and interactive manner. Applicants are advised to refer to the companion NOFO for more information about the roles and responsibilities of the HUB in TrialNet.

5. Collaborative Mechanistic Study Group (CMSP)

The TrialNet CMSP is a group of T1D and immunology experts (including some Clinical Center PDs/PIs and external consultants) who interact with the research community to provide guidance on TrialNet trials and mechanistic studies and enhance biomarker discovery in the context of TrialNet's mission. CMSP membership will be determined by the TrialNet Executive Committee, and will include the TNCC PD/PI, the TrialNet Chair, the TrialNet Vice Chair, the TrialNet HUB PD/PI and the NIDDK Project Scientist.

6. NIDDK Program Involvement 
 
The NIDDK Project Scientist assists the SC in carrying out all TrialNet studies. The Project Scientist provides scientific support to awardee activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications and overall performance monitoring. The NIDDK Project Scientist's and Program Official’s duties are as described in the Terms and Conditions of Award (below).

The NIDDK Technology Advancement Office is responsible for negotiating collaborative agreements with external partners, such as companies providing test agents. Communications with the FDA for IND approvals are handled through the NIDDK Office of Clinical Research Support. Consultations with both of these offices will be facilitated by the NIDDK Project Scientist and Program Official.

7. TrialNet Steering Committee (SC)

The primary governing body of the TrialNet network is the Steering Committee (SC), comprised of the Clinical Center PDs/PIs, the TNCC PD/PI, the TrialNet Chair and Vice Chair, the HUB PD/PI, the NIDDK Project Scientist and representatives from the TrialNet CMSP. New for the upcoming funding period, one representative from the community impacted by the disease (individuals with T1D, family members and friends of individuals with T1D) and one representative from T1D non-profit groups (JDRF, ADA, Children With Diabetes, etc.) will be included as members of the SC.

The TrialNet SC is responsible for designing network research activities, establishing priorities, developing common protocols and manuals, questionnaires and other data recording forms, establishing and maintaining quality control among awardees, reviewing progress, monitoring study accrual, coordinating and standardizing data management, and cooperating on the publication of results. Major scientific decisions regarding the core data will be determined by the SC. The SC will document progress in written reports to the NIDDK and will provide periodic supplementary reports upon request.

Specific Areas of Research Interest

The most recent grant funding cycle included the disruptive and deadly COVID-19 pandemic, which prevented the launch of new trials evaluating immunomodulatory agents. In addition, shutdowns at clinical sites reduced screening/participation rates. However, new efficiencies and advances developed by TrialNet during the pandemic provide opportunities for increased productivity in the future. For example, most initial risk screening is now done using online tools, with at-home and community blood sampling, relieving some of the burden on participants and research staff. Importantly, in late 2022, the first disease modifying therapy for T1D was approved by the FDA for clinical use in those at high risk of progression to clinical T1D. This approval could make screening more acceptable to participants who may benefit from therapy. Furthermore, the wealth of data collected by TrialNet and other studies provides opportunities for improvements in both trial design and detection of those who may be eligible and could benefit from trial participation.

During this project period, TrialNet will continue its ongoing prevention and new-onset trials. In addition, TrialNet will plan and prioritize new prevention and new-onset trials and studies. The exact number of protocols supported during the project period will depend on the nature and extent of the investigations proposed and the availability of funds. In addition, the network will continue to plan for and perform mechanistic studies in conjunction with trials as well as provide access to samples and participants from TrialNet clinical studies. This will generate information to improve understanding of the pathophysiology of T1D and to identify biomarkers to serve as intermediate study endpoints, enabling intervention earlier in the disease process, shorter trials using fewer participants, and the potential for interventions tailored for specific pathogenic mechanisms.

In accordance with the Regulatory Policies and Guidance under NIDDK Policies for Clinical Researchers, which defines the roles and responsibilities of the TNCC (https://www.niddk.nih.gov/research-funding/human-subjects-research/policies-clinical-researchers), the TNCC is responsible for:

• oversight and coordination of Clinical Center activities, including supporting development of the Clinical Centers and implementing studies and trials conducted by the network of Clinical Centers and Affiliates Sites;
• oversight of implementation of and adherence to protocols;
• coordination of communication among and with the Clinical Centers and Affiliate Sites;
• management of the collection and analysis of genetic, immunologic, pathogenic, clinical and biological samples and data from the clinical sites;
• training and certification of staff, and maintenance and updates of the Manuals of Operations for each TrialNet trial;
• maintaining the TrialNet internal and public websites in collaboration with the HUB;
• organizing and preparing reports for TrialNet SC meetings, Data Safety Monitoring Board (DSMB) meetings, External Evaluation Panel (EEP) meetings, and other meetings and workshops as necessary;
• collection and management of all clinical and laboratory data, and for ensuring subject confidentiality, safety and quality control;
• ensuring that the design of studies and trials, including their primary outcomes, are scientifically sound and are supported by appropriate statistical evaluations;
• providing biostatistical and analytic expertise and conducting data analysis and interpretation (in conjunction with the TrialNet network investigators) of the data generated by TrialNet studies;
• guiding development of the statistical analysis plan for each TrialNet study or trial as a whole and for each manuscript reporting pre-specified primary and secondary outcomes;
• overseeing and facilitating communication between the Drug Distribution Center and the Clinical Centers (and Affiliate Sites) to ensure the timely supply of trial drug according to the protocols;
• transferring all data and biosamples generated by TrialNet to the NIDDK Central Repository per NIH and NIDDK Resource Sharing policies;
• engaging a broader set of investigators external to the immediate TrialNet group to provide opportunities to analyze data and participate by means of ancillary studies;
• developing opportunities for local analysis of data by TrialNet investigators and other qualified researchers at their institutions, and investigators outside the TrialNet group ("disseminated data analysis"); and
• abiding by the network Duality of Interest Policies and Procedures and implementing procedures requiring TrialNet investigators and others to identify financial and other conflicts of interest on a routine basis, at least annually, and share this information with NIDDK.

The TNCC will engage independent peer reviewers to help select Clinical Centers to screen the relatives of people with T1D and enroll those eligible and interested into TrialNet prevention and new-onset studies. 

• Clinical Centers will be represented as voting members on the TrialNet SC, which evaluates and approves every TrialNet study. 
• Some, but not all, Clinical Centers will oversee Affiliate Sites, and Clinical Center/Affiliate Site distribution will be organized to optimize coverage of North America.
• Successful Clinical Center applicants will demonstrate the ability to efficiently screen, recruit, treat and follow subjects in T1D prevention trials and should incorporate active and innovative approaches to improving screening and enhancing trial participation.
• Clinical Center Program Directors/Principal Investigators (PDs/PIs) are expected to participate as members of the TrialNet SC as well as on TrialNet’s operational committees (individual trial committees, manuscript committees, clinical operations committees, laboratory monitoring committee, ancillary studies committee, etc). 
• Clinical Center PDs/PIs should have expertise in T1D etiology and pathogenesis as well as the willingness to engage in potentially challenging but scientifically strong interventions and studies that advance the field toward its goal of T1D prevention.
• Clinical Centers will be chosen based on their ability to screen and recruit trial participants and implement study protocols.
• Only applications from North American institutions will be considered, and all U.S. sites must be willing and able to utilize TrialNet's central IRB (OneIRB).
• Clinical Centers must propose at least one Coordinator at no less than 6 person-months devoted exclusively to TrialNet, and total PD/PI effort at each Clinical Center must not exceed 3.6 person-months.
• Funding levels for selected Clinical Centers will be re-evaluated yearly based on individual site productivity and available opportunities.
• Funded Clinical Centers must demonstrate their intention to actively participate in all TrialNet prevention trials and should participate, when possible, in ancillary studies and partnered new-onset trials.
• Geographic distribution of network centers should be considered in the choice of Clinical Centers to ease subject burden and reduce network costs related to travel.

Plan for Enhancing Diverse Perspectives (PEDP)

• This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV).
• Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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 Organizations) 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• 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 NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

John Connaughton, PhD
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 How to Apply – Application Guide and the Table of Page Limits must be followed.

For this specific NOFO, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the How to Apply – 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:

Plan for Enhancing Diverse Perspectives

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
• The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate.
• Where possible, applicant(s) should align their description with these required elements within the research strategy section.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review.

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups historically under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp.

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.

PEDP implementation costs

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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:

Specific Aims: Applicants must list and describe the specific aims of the TNCC including but not limited to items listed below.

Research Strategy: The application must address the following functions in subsections as described below.

TrialNet Significance

The applicant must explain the network's continued importance, critical need, scientific premise and impact.

Continuation of Ongoing Studies and Development/Implementation of New Studies

The applicant must:

• describe their experience, plans and strategies for the development and implementation of new prevention and new-onset trials as well as plans for supporting the continuation and completion of ongoing trials, including but not limited to: (1) screening relatives of individuals with T1D for monitoring and possible inclusion in intervention studies aimed at preservation of insulin-producing cells; (2) design, conduct and continuation of intervention studies in individuals at risk for the development of clinical T1D and in individuals with new-onset T1D; and (3) management of research projects in varying stages of development, implementation and completion; and
• describe their experience, plans and strategies for supporting ongoing mechanistic and operational studies as well as the development and implementation of new mechanistic and operational studies, including studies being done in conjunction with trials as well as mechanistic and operational studies to inform study design independent of individual clinical trials.

Selection and Oversight of Clinical Centers and Affiliate Sites

The applicant must describe how the TNCC will:

• conduct an open competition (issuance of Request for Proposals; RFP) to select approximately 10 to 20 Clinical Centers that will screen and recruit participants into trials and implement trials selected by the SC;
• ensure that Clinical Center applications include active and innovative approaches to improving screening and enhancing trial participation and demonstrate their ability to efficiently screen, recruit, treat and follow subjects in T1D prevention trials;
• ensure that Clinical Center PDs/PIs will actively participate as members of the TrialNet SC as well as on TrialNet’s operational committees (individual trial committees, manuscript committees, clinical operations committees, laboratory monitoring committee, ancillary studies committee, etc.); 
• ensure that Clinical Center PDs/PIs have expertise in T1D etiology and pathogenesis as well as the willingness to engage in potentially challenging but scientifically strong intervention trials and studies that advance the field toward its goal of T1D prevention;
• ensure that many of the Clinical Centers are in a position to oversee Affiliate Sites and that the distribution of Affiliate Sites is organized to optimize geographic coverage in North America;
• ensure that selected Clinical Centers (only North American sites are eligible) are willing and able to utilize TrialNet's central IRB (OneIRB) (this applies to U.S. sites only);
• establish funding levels at the selected Clinical Centers and how they will be adjusted annually during the grant cycle;
• ensure that selected Clinical Centers will actively participate in all trials and will participate, when possible, in ancillary and partnered new-onset trials;
• consider geographic distribution in the choice of Clinical Centers to ease participant burden and reduce network costs related to participant travel; 
• engage independent peer reviewers to help select Clinical Centers in the open competition; and
• monitor the Clinical Centers and ensure quality assurance with respect to the performance of the Clinical Centers throughout the project period.

Oversight and Coordination of Clinical Center Activities

The applicant must state their support of collaborative research and their willingness to participate in a collaborative and interactive manner with the Clinical Centers, the HUB and the NIDDK and its partners (academic, non-profit, industry, etc.).

The applicant must describe: 

• plans for data-driven oversight and coordination of Clinical Center activities, including supporting Clinical Center development as well as implementation of and adherence to studies conducted by the network of Clinical Centers and Affiliates Sites; 
• plans regarding the approach to identification, screening and recruitment of participants, including those from backgrounds currently underrepresented in TrialNet clinical trials (see PEDP guidance); 
• plans for the evaluation of recruitment and development/testing of innovative strategies to increase recruiting;
• plans to enhance network coordination to accelerate the timeline for trial launch and rigorous, rapid reporting and publication of results;
• how Clinical Center and Affiliate Site staff will be trained and certified; and
• how Manuals of Operation will be maintained and updated for each TrialNet trial.

Collaborative Leadership Plans

The applicant must describe:

• how management and collaborative leadership will be accomplished within the structure of the TrialNet network;
• how potential network colleagues (from academia, non-profit organizations or industry) will be introduced to TrialNet, supported in the study conception phase and integrated into the network in the planning and implementation phases;
• their consistent collaborative leadership in recent multi-center trials in T1D prevention and evidence of experience in and willingness to participate in this collaborative program; and
• any special expertise or unique strengths they can offer to the collaborative effort, for each state of T1D protocol development and implementation, to meet the challenges and opportunities in TrialNet.

Coordination of Communication

The applicant must describe how they will coordinate communication among and with the Clinical Centers, Affiliate Sites, HUB and NIDDK.

For example: 

• how they will maintain the TrialNet internal and public websites in collaboration with the HUB;
• how they will oversee and facilitate communication between the Drug Distribution Center and the Clinical Centers (and Affiliate Sites) to ensure the timely supply of study agent according to the protocols;
• their experience in maintaining excellent and seamless communication and coordination of complex multi-center trials; and
• innovations in their approach to collaborative and interactive communication across the TrialNet network, especially from the clinical point of view, including interactions with Clinical Center and Affiliate Site staff to enhance TrialNet operations.

Study Design, Data Coordination and Statistical Analyses

The applicant must describe: 

• the experience of their research team and any additional research expertise upon which they can draw, in addition to the resources at their institution;
• how they will ensure that the design of studies, including their primary outcomes, are innovative, scientifically sound and supported by appropriate statistical evaluations;
• how they will provide biostatistical and analytic expertise and conduct data analysis and interpretation (in conjunction with the TrialNet network investigators) of the data generated by TrialNet;
• how they will use innovative, novel statistical approaches to the design of new trials to increase trial efficiency to, for example, decrease numbers of participants needed, complete studies more quickly and include populations that are currently underrepresented in TrialNet (see PEDP guidance);
• how the TNCC will support opportunities for local analysis of data by study investigators and other qualified researchers at their institutions as well as investigators outside of the study group ("disseminated data analysis");
• how they will guide development of the statistical analysis plan for each TrialNet study as a whole and for each manuscript reporting pre-specified primary and secondary outcomes; and
• how they plan to use information from TrialNet for purposes including, but not limited to:
  • improve understanding of the pathophysiology of T1D; 
  • identify biomarkers to serve as intermediate study endpoints to enable intervention earlier in the T1D disease process;
  • shorten trials by using fewer participants, etc.; and 
  • testing interventions tailored for specific pathogenic mechanisms.

Engagement of Research Partners

The applicant must describe:

• how they plan to engage investigators external to the immediate study group to provide opportunities for partners to collaborate on new trials, to share data and ideas and participate in TrialNet by means of ancillary studies; and
• how they plan to engage community research partners, such as community members impacted by the disease (individuals with T1D, family members and friends of individuals with T1D) and representatives from T1D non-profit groups (such as JDRF, ADA, Children With Diabetes, etc.), to participate as active members of the SC (to be involved in the development, implementation and publication of TrialNet trials).

Data and Sample Management

The applicant must describe: 

• how they will manage the collection and analysis of genetic, immunologic, pathogenic, clinical and biological samples and data from the clinical sites;
• how they plan to transfer all data and biosamples generated from TrialNet studies to the NIDDK Central Repository per NIH and NIDDK Resource Sharing policies;
• how clinical and laboratory data will be collected and managed and how subject confidentiality, safety and quality control will be ensured; and 
• how they will handle data and sample management, including standardized acquisition, quality control, dissemination, and public accessibility.

Ensuring Management of Dualities of Interest

The applicant must describe how they will enforce network Duality of Interest Policies and Procedures and implement procedures to require study investigators and others to identify financial and other conflicts of interest on a routine basis, at least annually, and share this information with the NIDDK Program Staff.

Inclusion of Early-Stage Investigators

Since TrialNet's goals for durable T1D prevention are long term, it is necessary to ensure a workforce pipeline to participate now as well as take up leadership in the future. 

The applicant must describe plans for meaningful inclusion and participation of diverse early-stage investigators in a variety of TrialNet activities, such as Clinical Centers, TNCC, Chair’s office, Laboratories, Committees (Protocol, Mechanistic, Steering, Laboratory Monitoring, Publications, etc.).

Plans to Increase Inclusion of Diverse Participants (see PEDP guidance)

The applicant must describe plans and a proposed budget for the design and implementation of programs to increase the diversity of TrialNet participants. Details must be provided regarding the approach to identification, screening and recruitment of participants from backgrounds currently underrepresented in TrialNet. This is especially important since recent data demonstrates that T1D incidence is rising fastest in children from minority groups, while those groups are currently underrepresented in TrialNet trials.

Succession Plan

The applicant must describe a comprehensive succession plan in the application. The applicant must include an assistant TNCC PD/PI with a plan for their involvement that would allow them to fulfill the TNCC PD/PI duties as needed. A multi-PI organizational structure would also be acceptable if TNCC PD/PI duties are equally shared/interchangeable if circumstances require.

Letter of Support: Institutions will be required to document commitment to the PD(s)/PI(s) by providing departmental and institutional support letters. In addition, applicants are encouraged to demonstrate support via other means (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD(s)/PI(s)). Because current and prospective Clinical Centers will be submitting applications in response to the RFP(s), letters of support from current and prospective TrialNet Clinical Center personnel are not allowed.

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.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Resource (Biological Sample) Sharing Plan.

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.
• The TNCC application should include an overall sharing plan for data generated during the funding of TrialNet. The plan should specifically indicate what will be shared, by what means it will be shared, and the conditions that will apply to recipients of shared data.

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Information on the submission process and a definition of on-time submission are provided in the How to Apply – 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 Section 7.9.1 Selected Items of Cost.

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.

Applications must include annual PEDP milestones. Applications that fail to include annual PEDP milestones will be considered incomplete and will be withdrawn. Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

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

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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.

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 National Diabetes and Digestive and Kidney Diseases (NIDDK) 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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

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

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

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

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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:

• Federalwide Standard Terms and Conditions for Research Grants
• 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.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the HHS Office for Civil Rights website.

HHS recognizes that NIH 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.

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 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 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 clinical 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 policies and network/consortium 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 network/consortium policies, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network/consortium studies between grantee and third-party will be provided to the NIDDK Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network/consortium policies. Further, at the request of the NIDDK Program staff, any other network/consortium-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: “Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions)”, and Section 8.5.2, titled: “Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support”, noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.”

9. Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and network/consortium activities that includes access to any network/consortium generated resources (i.e., data and bio-samples), or study results that are not publicly available, or using the name of the network/consortium or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.

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 or network/consortium. 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/Project Coordinator 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 and Safety Monitoring Board (DSMB), 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. Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the notice of award.

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 Scientist or 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 or Project Coordinator 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 or Project Coordinator. 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 and the Project Coordinator will have non-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 Steering Committee.

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 or Project Coordinator may not serve as Chairperson. The NIDDK Program Official will review the Committee’s selection for potential bias, conflicts of interest, or lack of required expertise. If the Program Official has concerns regarding selection of the Chairperson which are not satisfactorily resolved, the Program Official may withhold concurrence if approved by the Director, Division of Extramural Activities, NIDDK based on written justification. In cases where Program Official concurrence is withheld, the Steering Committee will be required to make another selection.

External Consultants

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

Dispute Resolution

Any 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 recipient (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 recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 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.

• Recipients will provide updates at least annually on implementation of the PEDP.

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 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), 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 2 CFR Part 200.113 and Appendix XII to 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 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: 301-637-3015

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]

Cheryl K. Nordstrom, PhD, MPHS
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-6711
Email: [email protected]

Natasha Loveless
National Institute of Diabetes and Digestive and Kidney Diseases
Telephone: 301-594-8853
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 2 CFR Part 200.

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