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 How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

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

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

This NOFO invites applications for investigator-initiated, high-risk multi-center therapeutic clinical trials conducted at one or more clinical centers. A multi-center study is classified as “high risk” if it utilizes either a high-risk intervention or has high operational risk, or both. NOT-DK-20-051 provides an explanation of high-risk versus low-risk studies.

Proposed trials should be hypothesis-driven and focus on a disease relevant to the mission of NIDDK, including trials to address diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders and obesity; and kidney, urologic, and hematologic diseases. Proposed trials are expected to improve understanding, diagnosis, prevention, or treatment of the diseases being studied, and should focus on research questions likely to change clinical practice and/or improve public health.

NIH defines a clinical trial as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes" (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html). Only applications proposing therapeutic clinical trials will be supported by this NOFO. This NOFO is not appropriate for and will not support mechanistic clinical trials. A therapeutic trial has a goal of determining clinical safety, tolerability, efficacy and/or effectiveness of an intervention. Such studies may be pragmatic trials where the intervention is tested under the usual conditions in which it will be applied, or explanatory trials where the intervention is tested under idealized circumstances. Mechanistic trials are designed to understand a biologic process, the pathophysiology of a disease, or the mechanism of action of an intervention.

Examples of trials that are consistent with the intent of this NOFO are:

• Clinical trials that test the safety, tolerability, dosing and/or efficacy of a new or re-purposed pharmacologic, biologic or surgical intervention, or a unique combination of therapies;
• Clinical trials to improve processes of care;
• Clinical trials of behavioral interventions to prevent disease, promote treatment adherence, and improve disease management or treatment;
• Clinical trials designed to test a biomarker, diagnostic test, or medical device that would improve disease/outcome risk-stratification, diagnosis, treatment or monitoring of treatment responses;
• Comparative effectiveness/pragmatic clinical trials of previously established therapies and/or testing the effect of these therapies among disease sub-groups.

For the purpose of this NOFO, a clinical research center may encompass one or more physical locations where the clinical trial is being conducted -- i.e., where study participants are recruited, and/or are intervened upon and/or have outcomes assessed under a single protocol – as long as all locations are under the overall direction of a single investigator. A data coordinating center is not considered a clinical research center.

Definition of Risk

As explained in NOT-DK-20-051, the risk level of a study may be related to interventional and/or operational risk. The examples below provide general guidelines for risk assessment and are not exhaustive. Potential applicants are strongly encouraged to contact NIDDK staff to discuss their proposed study and determine the most appropriate mechanism for submitting their application.

Examples of high-risk interventions include:

• An intervention that has an unknown safety profile or has substantial side effects (including all studies requiring an IND/IDE application). This would include studies of a drug in a new population, or study of a licensed product for an unapproved indication;
• A complex or invasive intervention, including diagnostic procedures;
• A study involving complex assessment of multiple outcomes, including the ascertainment of outcomes using invasive research procedures;
• Pragmatic trials proposing significant changes to standard of care practices, or significant coordination with multiple care providers and healthcare data systems;
• A multi-center study involving more than minimal risk in vulnerable study populations (as defined in 45 CFR 46)

Studies that do not meet the above criteria will generally be considered to involve low-risk interventions. Low-risk multi-center studies usually include the administration/use of a licensed product for an approved indication, or the provision of a routine intervention that could be used in the setting in which it is being studied (e.g., a lifestyle intervention to promote weight loss).

Examples of multi-center studies with high operational risk include:

• An inexperienced investigator, defined by lack of experience in conducting clinical trials, coordinating research across multiple centers, or recruiting the population to be studied;
• A complex study design that involves standardization of research measures and outcomes collection and research data capture over multiple centers;
• A study that involves the establishment of agreements with third parties that intend to utilize research study data to support regulatory filings with the FDA

Multi-center studies that do not meet the above criteria will generally be considered to have low operational risk.

A multi-center study is classified as “high risk” if it utilizes either a high-risk intervention or has high operational risk, or both.

Applications for low-risk therapeutic clinical trials will not be supported by this NOFO and may be submitted to PA-20-183.This NOFO is also not intended for multi-center observational studies. High-risk multi-center observational studies which may be submitted as U01s to PAR-24-102  or other relevant NIH FOAs; low-risk observational studies may be submitted to PA-20-185 or other relevant NIH FOAs.

Overview of the NIDDK process for support of investigator-initiated, multi-center clinical trials:

NIDDK supports investigator-initiated, high-risk multi-center clinical trials through a two-part process: 1) implementation planning phase followed by 2) multi-center clinical trial cooperative agreement (U01). TEMP24336 NIDDK Multi-Center Clinical Study Implementation Planning Cooperative Agreements (U34) provides support for the planning phase; this NOFO addresses the funding for the clinical trial.

Part 1. Implementation Planning Phase

NIDDK will support clinical study planning (U34) cooperative agreements for high-risk multi-center therapeutic clinical trials. The U34 is intended to support all administrative study group activities that are required in order to begin recruitment of participants. These activities include, but are not limited to: establishing the research team, developing tools for data management and oversight of the research, defining recruitment strategies, finalizing the protocol and investigators brochure, writing of the Manual of Operations, establishing a data and safety monitoring plan, and initiating the IRB approval process.

It is expected that receipt of a U34 will lead to the timely submission of an application (U01) for support of the full-scale study, incorporating the elements developed during the planning period. The goal of the planning phase is to ensure that the clinical trial will be able to begin recruitment almost immediately, should a U01 be awarded.

Prospective applicants should note that funding of a U34 does not guarantee or imply funding for a subsequent U01 application.

Part 2. Multi-Center Clinical Study Cooperative Agreement (U01).

The U01 will support the conduct of the clinical trial.

Planning activities are not permitted as part of the U01 application. It is expected that planning work done during the U34 phase, or through some alternative funding mechanism, will allow the U01 applicant to initiate study staff training followed by study participant recruitment as soon as the U01 award is made. Applicants who feel they have completed all the planning elements without a U34 may apply directly for the U01. Further information regarding the U34/U01 process supported by these companion NOFOs, including a set of frequently asked questions (FAQs) can be found at: https://www.niddk.nih.gov/research-funding/human-subjects-research.

Applications should include only one clinical trial.

Many of the diseases or conditions within the mission of NIDDK disproportionately affect individuals from minoritized and underserved communities. NIDDK encourages research focusing on such populations, including individuals from racial and ethnic minority groups, rural populations, sexual and gender minority groups and other socioeconomically disadvantaged and medically underserved communities. NIDDK places a high priority on clinical studies to understand and eliminate health disparities and promote health equity.

NIDDK is committed to conducting clinical studies that have been developed in partnership with patients, community members, families, healthcare providers, organizations, and other relevant partners who are affected by or have a direct interest in the research (Pathways to Health for All: Health Disparities & Health Equity Research Recommendations & Opportunities - NIDDK (nih.gov)). Active and meaningful engagement should involve these individuals and/or organizations in the development, design, and execution of the study, as well as in dissemination of findings. Meaningful engagement must entail more than focus groups, surveys or other activities where people are only involved as participants or respondents. Rather, engagement approaches must involve bidirectional and sustained communication and interactions that result in informed decision-making about high-priority research needs and issues that are important to affected individuals, community members, and/or organizations, especially populations who disproportionately experience NIDDK mission diseases. Engagement activities that bring to bear the expertise and lived experience of affected individuals and diverse communities may yield interventional, recruitment and retention approaches that are more likely to be acceptable and effective, and less likely to cause harm. Engagement that involves trust building and repairing when needed, and use of culturally appropriate research approaches (i.e., identifying the health problem, design, and materials) is an important method to enhance and assess research outcomes including recruitment and retention goals, specific health outcomes, and sustainability of efficacious interventions. Ideally, affected individuals, groups, and organizations are not only “engaged,” but integrated equitably into the research team which includes appropriate orientation and onboarding support to the team, and compensation.

Since the complete study design and protocol must be included in the U01 application, it is expected that investigators can demonstrate substantial engagement and partnership with appropriate individuals, community members, and or organizations prior to the U01 submission.

This NOFO will only support research within the mission of NIDDK. Research applications in areas that are primarily within the missions of other NIH Institutes and Centers are not appropriate for this NOFO and will not be supported. NIDDK has many diseases within its mission, but all research related to relevant diseases may not be appropriate for NIDDK. Applicants to this NOFO are strongly encouraged to contact NIDDK staff as soon as possible in the development of the application and generally at least 12 weeks prior to the application date. NIDDK staff can help the applicant understand whether the proposed clinical trial is within the goals and mission of the Institute and is appropriate for this NOFO. As part of the consultation process, NIDDK staff will consider whether the proposed clinical trial meets the goals and mission of the Institute, whether it addresses one or more high priority research areas and meets programmatic needs, including balance across research areas, whether it is appropriate to conduct as an investigator-initiated clinical trial, and whether appropriate funds might be available for the clinical trial. During the consultation phase, if the proposed study does not meet NIDDK's programmatic needs or is not appropriate as an investigator-initiated clinical trial, applicants will be strongly encouraged to consider other Funding Opportunities. If NIDDK ascertains that substantial additional preliminary data or planning may be necessary, the applicant will be encouraged to consider applying for funding under the appropriate NOFO. You should contact the Program Director responsible for your area of research. If you are not certain whom to contact, you should reach out to the contact for the appropriate scientific division listed at the end of this NOFO, and you will be directed to the correct Program Director.

This consultation process is distinct from pre-approval requirements for applications with budgets of $500,000 or more direct costs in any year, as described in Section IV.7.

Applications Not Responsive to the NOFO

This NOFO will only support research within the mission of NIDDK. Research applications in areas that are primarily within the missions of other NIH Institutes and Centers are not responsive to this NOFO. Further information the NIDDK mission, including areas not covered by NIDDK, is available here.

Low-risk clinical trial applications (see NOT-DK-20-051) are not responsive to this NOFO. Low-risk clinical trial applications may be submitted to PA-20-183 or PA-20-184. Applications for low-risk observational studies may be submitted to the PA-20-185.

This NOFO will only support therapeutic clinical trials. Mechanistic clinical trials are not responsive to the NOFO and may be submitted to PA-20-183 or PA-20-184.

Applications involving animal or in vitro studies are not responsive to this NOFO.

Recruitment of participants exclusively from foreign sites is not allowed under this NOFO. Foreign components may provide scientific input (e.g., special data analyses or laboratory assays).

Non-responsive applications will not be reviewed and will be withdrawn from consideration.

Applicants are reminded of the 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), the federal requirement for use of a single IRB for cooperative research under 45 CFR 46.114, as well as the NIH policy on the registration and reporting of the results of clinical trials (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-149.html).

Applicants are encouraged to review NIDDK policies related to clinical research and cooperative agreements here.

Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

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 found here: https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp. 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, 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 How to Apply – Application Guide and the Table of Page Limits must be followed.

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.

Plan for Enhancing Diverse Perspectives (PEDP)

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.

The annual budget requested should match the timeline proposed for the project.

Because all applications must include detailed scientific and operational plans, funding needs for the entire trial and data analysis period must be included. Investigators must submit a complete, justified, individual budget for each year of support requested. All costs requested and all changes in budgets after the first year should be clearly identified and justified. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating site, if multiple sites or cores are proposed. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail along with supporting letters signed by individuals who have the authority to make fiduciary commitments on behalf of the institution (see Letters of Support in the PHS 398 Research Plan below). These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget or as Estimated Project Funding.

The application budget should include funds to support two DSMB meetings each year (see Section VI, Award Administration Information). Funds should also be included in the final year of the budget for archiving data and biosamples at the NIDDK Repository

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:

 Research Strategy: The applicant must clearly articulate the significance of the proposed study including why the clinical trial is needed and what evidence gap the trial will address, including a discussion of why there is clinical equipoise and how the results will impact clinical care and/or public health. The discussion of the trial's potential impact must include consideration of the developmental pathway of the intervention and next steps, beyond publication of results, needed to share findings with relevant end-users (e.g., health care providers, patients, healthcare systems and/or policy makers) and translate/disseminate the intervention.

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

The application must include a detailed description for the study design, addressing the scientific rationale for the intervention chosen, the population to be studied and the outcomes being assessed.

In addition, the application must address potential biases or challenges in the protocol and how they will be addressed.

There must be a description of all completed, ongoing and planned engagement efforts.

Letters of Support: A letter of support should be provided from all clinical centers, reading centers, central laboratories or other central cores or required study components. If co-funding or in-kind support is planned from non-NIH sources, letter(s) outlining details of the commitment (e.g., type, amount and source of support), signed by a business official on organization letterhead, must be included in the Letters of Support section. In addition, letters of support should be provided from engaged partners who have been involved in the development of the study and/or will continue to be involved during the conduct of the study.

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. 
• The NIDDK has established Central Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The investigator(s) should be prepared to transfer data and samples to the NIDDK Central Repository or to another NIDDK approved repository. 

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.

The Protocol for the full study must be submitted as part of the Appendix.

Applications that lack the Study Protocol are considered incomplete and will not be peer reviewed.

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 and anticipated yield from recruitment and screening efforts. Please provide a table showing the expected number and demographics of the population to be recruited at each site. This is distinct from the table with overall recruitment for the entire study, which should be provided in 2.9 Inclusion Enrollment Report (s). The plan should also include a discussion of past experience in recruiting and retaining similar populations, expected challenges to recruitment and retention, and possible contingency plans.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan:

In addition to the description of safety monitoring, address plans to monitor trial 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.

3.5 Overall Structure of the Study Team:

The applicant should include a detailed description of the study organization and administration. In addition to items delineated in the application instructions for the PHS Human Subjects and Clinical Trials form, this description should include, as applicable, a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed. If an advisory committee is planned, applicants should not contact or name potential advisory committee members. Renewal applications with Advisory Committees should include the names of all committee members during the past project period. The PD/PI should discuss in detail whether he/she has experience in the conduct and administration of complex studies, including delineation of the success of those studies in terms of recruitment, retention and publications.

Section 4 - Protocol Synopsis

 4.2 Outcome Measures

Please indicate all time points when an outcome measure will be collected.

 4.3 Statistical Design and Power

The sample size and statistical power calculations should contain enough detail, including a description of any assumptions made, so that a reviewer can readily duplicate the sample size. The power analysis should include a discussion of the anticipated level of adherence to the intervention and rates of follow-up (i.e., drop out/lost to follow up) during key outcome collection contacts. There should be a discussion of how missing  data will be handled. Any planned interim analyses should also be described.

Section 5 - Other Clinical Trial-related Attachments 

5.1 Other Clinical Trial-related Attachments

Milestone Plan: The filename "Milestone Plan.pdf" must be used for this attachment.

Applicants are required to provide detailed interim performance measures and timelines for completing key objectives and administrative functions for the proposed clinical trial(s), as applicable. Milestones should be easily measurable and realistic. Below is a list of potentially useful milestones; please tailor this list to each of your clinical trial aims and provide approximate dates or project year and quarters (e.g., Yr01/Q1, Yr01/Q2, Yr01/Q3, etc.) when each will be conducted/completed:

• Completion of all required regulatory approvals (e.g., IND/IDE from the FDA or agencies in other countries)
• Finalize contracts/third party agreements
• Finalize clinical protocol(s) 
• Finalize consent forms
• Finalize recruitment materials, surveys and data collection tools
• DSMB approval
• IRB approval
• Finalize data entry forms/system
• Finalize training manuals and manuals of operations
• Good Clinical Practice (GCP) and other relevant technical training of study staff
• Training of staff on study protocol and procedures
• Registration of clinical trial in ClinicalTrials.gov
• Anticipated dates of:
  • Enrollment of the first participant
  • Enrollment of 25% of the target sample size
  • Enrollment of 50% of the target sample size
  • Enrollment of 75% of the target sample size
  • Enrollment of 100% of the target sample size
• Posting of consent forms on ClinicalTrials.gov
• Completion of intervention (i.e., date of last intervention visit)
• Completion of data collection (i.e., date of last study visit) 
• Completion of primary endpoint and secondary endpoint data analyses
• Completion of primary outcome paper
• Closeout plans/communication of results to participants
• Reporting of results in ClinicalTrials.gov

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.

Planning Activities: The filename "Planning Activities.pdf" should be used for this attachment.

The applicant  must provide a summary of all completed planning activities that have been competed in anticipation of beginning recruitment, should an award be made. These may include:

• Development of a Manual of Operations
• Development of case report forms
• Database  programming
• Development of the research team
• Identification of clinical sites
• Identification of a central laboratory and other relevant service cores
• Development of study organization and governing principles, if appropriate, including a Publications Policy and an Ancillary Studies Policy
• Development of training materials and policies for staff certification and site initiation
• Initiation of the IRB review process
• Obtaining study drug or other intervention materials, if appropriate
• Obtaining an Investigational New Drug Application or Investigational Device Exemption, if appropriate
• For U34 awardees, this section should highlight any changes to the protocol made after the submission of the U34 application; key decisions made during the U34 funding period, including a delineation of all changes recommended by NIDDK, including those made following input from a study Data and Safety Monitoring Board (DSMB) or External Evaluation Panel (EEP).

Applications that lack a Planning Activities section are considered incomplete and will not be reviewed.

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 the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

Applications must include annual milestones. Applications that fail to include annual 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.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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.

Specific to this NOFO:

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 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: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• 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.
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 or Project Coordinator 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 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.

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: 301-480-7075

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

Tracy Rankin, Ph.D., M.P.H.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4748
Email: [email protected]

Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-0021
Email: [email protected]

Aynur Unalp-Arida, M.D., Ph.D.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8879
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Todd Le
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7794
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.