Part 1. Overview Information

Key Dates

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

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

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

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

This FOA aligns with the Mission and Vision of the NIDDK Strategic Plan for Research, including the charge to develop and evaluate strategies to mitigate the adverse effects of social determinants of health and the theme of empowering a multidisciplinary workforce, engaging a broad array of stakeholders, and pursuing pathways to health for all. Additionally and within this, the NIDDK strongly encourages Research on Sex/Gender Differences, Sexual and Gender Minority-Related Research and Race/Ethnic Diversity (see NOT-DK-22-003).

Background

Despite significant advances in medical treatment for T1D, racial, ethnic, and socioeconomic disparities persist in all facets of living with type 1 diabetes (T1D) including general glycemic control, acute and chronic complications, and patient reported outcomes such as quality of life. Factors contributing to health disparities are complex and multifactorial. Decades of research indicate that adverse social, environmental, and economic factors, known as the negative social determinants of health (SDoH), may more powerfully shape health outcomes than other factors (e.g., medical care, biology). It is critical to understand and address the myriad of factors that impose constraints on the ability of an individual to achieve optimal health including optimal control of their diabetes. In general, adverse living conditions, including overcrowding, isolation, inadequate access to healthy food, transportation barriers, and unstable housing, are linked to poor health outcomes and mortality. Exposure to such health-impeding SDoH or social risks negatively contributes to obesity, diabetes, and kidney disease outcomes that disproportionately affect racial/ethnic minorities and other socially disadvantaged communities. Negative SDoH and social stressors related to the prompt identification (or lack thereof) and management of T1D are numerous. Examples include: housing/neighborhood conditions, lack of access to quality foods and nutrition, lack of access to transportation to pharmacy & medical appointments or educational classes (such as those required for T1D device technology use) and facilities for safe physical activity. Additionally, deficits in other health promoting resources such as adequate space and privacy within employment and educational settings for diabetes self-care can negatively impact T1D management. Social risks and needs are particularly impactful for T1D which is a chronic, labor intensive disease requiring complex treatment regimens. Indeed, the daily complexity of these treatment regimens may be difficult to adopt in the face of pressing social risks.

In 2019, the National Academies of Sciences, Engineering and Medicine issued a consensus report which found that integrating social care into healthcare delivery holds the potential to achieve better health outcomes for the nation The report noted that five activities are required to integrate social care into healthcare delivery: 1) awareness activities that identify social risks and needs; 2) adjustment activities of the clinical care team to accommodate identified social barriers; 3) assistance activities to reduce social risk by connecting patients with social care resources; 4) alignment activities that enable healthcare systems to understand and leverage their communities existing social care assets; and 5) advocacy activities that bring healthcare and social care organizations together as partners.(link)

Experts in this field assert that approaches to identify and address negative SDoH may help accomplish numerous care goals: expand providers ability to tailor treatment to individual patient needs, intensify effects of existing treatments, help patients follow medical regimens, improve patient-provider communications, and promote health equity in chronic disease prevention and treatment. However, fundamental scientific research gaps in achieving these goals remain, including optimal screening/management processes and workflows for identification of negative SDoH that most impact health, optimal time horizons for detecting health changes, how to consider patient-reported experiences, and how to develop robust partnership models with high potential for sustainability.

Research in this area is made possible by the growing awareness of the impact of adverse SDoH on health outcomes, leading to growing interest and capabilities on the part of healthcare systems to address negative SDoH within the context of medical care. For example, newer care models implemented in Medicare, Medicaid and other payer programs capitalize on existing resources by incentivizing healthcare systems to treat the whole person and create strategies that bridge medical care with community resources. In addition, advances in health information technology (IT) make it possible to establish efficient screening and referral programs. These investments have led to a surge of interest in implementing SDoH interventions within clinical care services. However, despite this attention and attempts to integrate medical and social care within clinical services, little evidence exists to guide healthcare systems in how to best develop and adopt such models.

This FOA is designed to advance the science of integrating social and medical care through interventions that identify and address negative SDoH. Such interventions should help achieve health equity in T1D, especially among NIH-designated populations that experience health disparities. The goal of this initiative is to initiate a program that fosters pragmatic research efforts and stimulates collaborations between healthcare systems, community-based organizations, and social service entities for testing of social-medical integration interventions.

Research Objectives

Pilot and feasibility trials funded through this initiative will study interventions that involve screening for and assisting with negative SDoH through referral services within a healthcare encounter. Screening for social risks and needs must be accompanied by referral for (or referral for and provision of) resources to meet identified social needs. Endorsed social risks and needs could be addressed by appropriately referring or navigating patients to social resources using service organizations located externally or co-located within the healthcare system. The trials must determine 1) feasibility of screening for social risks and implementing referral service linkages (e.g., connecting persons in need to appropriate transportation, housing, food, etc. resources) within the context of a healthcare encounter, and 2) preliminary signals of the intervention’s impact on the social risk(s) and T1D health outcomes. As pilot trials, the long-term goal is to acquire preliminary data to support the rationale, design, and feasibility of a fully powered clinical trial. It is expected that through this opportunity successful pilot trials will lead to fully powered efficacy trials of the piloted interventions which may improve T1D health outcomes for people affected by negative SDoH.

Proposals should leverage partnership models between the healthcare sector, community resources such as social service organizations, and relevant stakeholders (e.g., people living with T1D, medical, community, and home-based practitioners, researchers, local businesses, etc.). Additionally, the expectation is that the social need(s) referral(s) will not represent a unilateral action from the healthcare provider team but will be part of an ongoing communication loop among the healthcare team, patient, and social service/community organization(s). In addition, the processes put into place for screening and referral should promote social needs informed care i.e., the healthcare team should develop a care plan that accommodates the social context of the patient and can adapt over time as social needs are met or change.

While direct preliminary data supporting the proposed intervention are not required, there should be data from the PD/PI or from the literature to support the premise and rationale for the pilot trial. There should also be evidence that the PD/PI or co-investigators have the requisite knowledge, skills, and experience to conduct the trial. This includes expertise in the nuances of health equity research including critical topics such as the role of implicit bias and structural racism which are often correlated with disproportionate social risks and needs. To this end, applications should include a multidisciplinary research team with a broad array of relevant expertise and research experiences, including appropriate healthcare expertise, health equity and disparities researchers, people living with T1D, and/or community-based/lived-experience organization representatives.

Grant funds may not be used to build new screening tools, although refinement of these tools may be done before starting the trial. Likewise, the collaboration model and entities (healthcare system, referral organizations) must be in place prior to application. Although some formative work may be appropriate, the purpose of this FOA is to support pilot and feasibility testing of the proposed intervention and not for intervention development. Studies will be allowed up to 6 months of the award period to conduct some formative and preparatory work for the trial (e.g., strengthening and refining collaborative partnerships; refining screening and referral protocols). However, it is expected that appropriate stakeholder and collaborative partnership involvement will have been done throughout the planning and development of the grant application prior to submission. Funding to support building health IT systems or directly provide social services is not allowed. While mixed qualitative & quantitative measures are encouraged, at a mimum, the trials must measure an objective, clinically meaningful outcome for T1D (such as a measure of glycemic control or rate of a diabetes specific complication such as diabetic ketoacidosis) and the status of the social risk(s)/needs endorsed (i.e., improved or not). Additionally, trials should be pragmatic for the potential of long-term sustainability. As such, it is expected that the intervention will enhance and/or support equitable partnership models between healthcare delivery and the social services sectors to build community-linkages that foster mutually beneficial and sustainable services beyond the funding period.

Proposed trials may test a single approach to screening and linkage or may be designed to determine optimal strategies for screening, linkage, and uptake of resource referrals. Examples of social resource referrals include, but are not limited to:

• Referral to a food bank or other services to address food insecurity in coordination with medical nutrition therapy (e.g., medically tailored diets to improve glycemic control in diabetes).
• Referral to resources to address housing insecurity or housing quality (e.g., United States Department of Housing and Urban Development-supported or community housing programs).
• Referral to or provision of transportation services which may alleviate transportation barriers to medical associated activities.
• Referral to existing national and local programs (e.g., home visiting programs, United States Department of Agriculture, Supplemental Nutrition Program of Women, Infant and Children WIC ) that can address multiple social needs which hinder efforts to manage T1D.
• Referral to pharmacy assistance programs to address financial barriers to obtaining insulin or prescribed medical technology.

Applications are expected to use community engagement approaches in designing and implementing the proposed trial and to clearly describe the process they have enacted and will continue to use to facilitate meaningful sustainable collaboration with people living with T1D, caregivers, family members, community members, community-based organizations, clinicians, healthcare systems, social service sector liaisons, and other relevant stakeholders throughout the research process. Meaningful engagement must entail more than focus groups, surveys, or other activities where stakeholders are only involved as respondents. Furthermore, authentic engagement and meaningful partnership with communities who disproportionately experience social risk are essential to effective health equity interventions. Failing to ensure research is founded on the wishes and realities of the people who will be most affected by the intervention(s) may ultimately produce more harm than benefit.

Investigators are strongly encouraged to employ an equity lens to guide their intervention development and implementation. Employing an equity lens considers at each decision point how processes, values, assumptions, actions, and interventions may: 1) affect meaningful involvement, inclusion and participation of people from NIH designated health disparity populations, and 2) mitigate or exacerbate inequalities in opportunities and outcomes. This is especially needed for communities who experience historical and contemporary forms of marginalization, discrimination, or oppression. An equity lens also acknowledges that health is affected by contexts external to the individual, including laws, policies, and other structural/social determinants of health. An equity lens also views individuals and populations through an asset-based frame that recognizes their strengths and resources.

Applications Not Responsive to the FOA

This FOA will only support T1D research. Applicants to this FOA are strongly encouraged to contact NIDDK staff as soon as possible in the development of the application, so that 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 FOA.

The following types of studies are not responsive to this FOA and will not be reviewed:

Observational studies are not responsive to this FOA. Applications for low-risk observational studies may be submitted to the PA-20-185.

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

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

Investigators who already have adequate preliminary data to support a fully powered clinical trial should consider PA-20-183, Research Project Grant (Parent R01 Clinical Trial Required).

Applicants are reminded of the NIH policy on the use of a single Institutional Review Board for multi-center clinical trials (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-004.html) as well as the NIH policy on the registration and reporting of the results of clinical trials (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-149.html).

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 FOA.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

Page Limitations

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

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy

The applicant should clearly articulate the significance of the proposed study including why the pilot trial is needed, and what evidence gap the trial will address. Investigators should clearly articulate why the long-term goal of the study is of high clinical significance and how data obtained in the pilot and feasibility trial will be used in a future clinical trial to improve T1D health outcomes i.e., a hypothesis-driven "next step" should be proposed. The proposal of next steps should include a discussion of the potential for sustainability and dissemination beyond a research award.

Although direct preliminary data are not required, any discussion of supporting data that provide the basis for the trial should address the adequacy and quality of previous studies.

The application should include a detailed description and scientific rationale for the study design, addressing the intervention chosen, the population to be studied and the outcomes being assessed. The design should include a description of how screening for social risks will be accomplished and how patient-identified social needs and preferences will be determined. There must be clear feasibility objectives and clear criteria for how feasibility will be assessed and judged to be successful. Investigators should consider how to determine acceptability of the proposed intervention to all stakeholders, including the input of people living with T1D, providers, healthcare systems and social service providers. There must be an assessment of whether the identified social risks/needs have been addressed or mitigated and whether T1D health outcomes have been affected. While it is not expected that these pilot and feasibility studies will be fully powered, investigators must collect data on objective T1D outcomes that would be critical in a subsequent fully powered trial, such as a marker of glycemic control or rate of T1D complications.

The application should address the feasibility of the proposed clinical trial including the available resources, access to the relevant population, and expertise in conducting human subjects research within the investigative team.

Applicants must describe in detail the role and extent of partnerships with community-based organizations and with individuals engaged to provide input and help shape the design and implementation/conduct of the proposed study. The details of this must be described within the Stakeholder Engagement Plan, attached separately, see section 5.1 Other Clinical Trial-related Attachments .

Letters of Support: Letters of support must be provided from all participating clinics, healthcare systems and/or hospitals, and all community or other organizations to which social risk/needs referrals will be made. In addition, letters of support should be provided from stakeholders who have been involved in the development of the study and/or will continue to be involved during the conduct of the study. All applications, regardless of the amount of direct costs requested for any one year, should address a Data 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.

Appendix:

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Applications should include a discussion of the availability of potential participants for the proposed study and anticipated yield from recruitment and screening efforts. If there is more than one recruitment site, please provide a table showing the expected number and demographics of the population to be recruited at each site and overall. The plan should also include a discussion of past experiences in recruiting and retaining similar populations, expected challenges to recruitment and retention, and possible contingency plans.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

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

Section 4 - Protocol Synopsis

4.2 Outcome Measures

The application should address all time points when an outcome measure will be collected.

4.3 Statistical Design and Power

Pilot and feasibility trials are, by definition, not fully powered to answer a question. The investigator should provide a rationale for the number of participants who will be studied. If a full power calculation is provided, the sample size and statistical power calculations should contain enough detail, including assumptions made, so that a reviewer can readily duplicate the sample size. The application 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. A discussion of how missing data will be handled should be included. Any planned interim analyses should also be described.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Other Attachments:

1. The filename "Milestone Plan.pdf" should be used for this attachment. Please amend the file name when more than one attachment with the same file name would be possible (e.g., Milestone Plan.1 for Study Record 1, Milestone Plan.2 for Study Record 2, etc.), if applicable.

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. The Milestone Plan is not the same as the Study Timeline (section 2.7). Milestones should be included for both phase 1 (formative phase) and phase 2 (trial execution) and may include, as applicable, but are not limited to:

• Engagement timeline for key stakeholder relationships
• Completion of data collection from stakeholders for intervention refinement (i.e,. completion of phase 1)
• Finalization of the clinical trial protocol(s) and informed consent/assent forms (with program director agreement, if applicable) and IRB approval
• Registration of the clinical trial(s) in ClinicalTrials.gov
• Completion of all required regulatory approvals (e.g., Investigational New Drug Application from the Food and Drug Administration)
• Contracts/third party agreements, including intervention product supply
• Training of study staff
• Completion date for finalizing the approach for the pilot intervention
• Anticipated date of enrollment of the first participant
• Randomization of 25%, 50%, 75% and 100% of the target sample size
  • Follow-up visit completion, if applicable of 25%, 50%, 75% and 100% of the enrolled or randomized study population, including women, minorities and individuals across the lifespan
• Expected drop-out or lost-to-follow-up rate overall, or by treatment arm
• Anticipated rate of adherence to the intervention(s)
• Completion of stakeholder midway-progress feedback (recruitment/retention progress)
• Completion of data collection
• Completion of primary endpoint and secondary endpoint data analyses
• Completion of final stakeholder feedback communication
• Completion of final study report and manuscript submission
• 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 do not include a Milestone Plan are incomplete and will not be reviewed.

2. The filename "Stakeholder Engagement Plan.pdf" should be used for this attachment.

The application must describe stakeholder engagement activities already conducted and how these activities influenced development of the protocol or proposed study conduct, including recruitment.

Applications that lack the Stakeholder Engagement Plan are considered incomplete and will not be peer 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 Policy on Late Application Submission.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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

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 the National Institute of Diabetes and Digestive and Kidney Diseases, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

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

Applications will be assigned 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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Institute of Diabetes and Digestive and Kidney Diseases Advisory Council. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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:

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

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

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

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

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

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

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

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

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

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

Not Applicable

3. Data Management and Sharing

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

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

4. Reporting

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

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

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

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

Section VII. Agency Contacts

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

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]

Miranda M Broadney, MD, MPH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-6841
Email: [email protected]

Cheryl K. Nordstrom, PhD, M.P.H.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 240-593-1733
Email:[email protected]

Eunica Haynes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-4018
Email:[email protected]

Section VIII. Other Information

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

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

This FOA is supported under the authority of P.L. 116-260, Consolidated Appropriations Act, 2021; Section 302. Diabetes Programs.