Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title
Understanding the Pathophysiology and Clinical Course of New-Onset Diabetes Following COVID-19 (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-DK-22-016
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.847
Funding Opportunity Purpose

This Funding Opportunity Announcement invites multiple Program Director/Principal Investigator (multi-PD/PI) applications to conduct a study to establish a longitudinal cohort of individuals who developed diabetes following SARS-CoV-2 infection to understand the pathophysiology and clinical course post-COVID-19 diabetes. The cohort must include children and adults and reflect the geography and demographics of COVID-19 in the U.S. There must be an appropriate comparator population recruited and followed. The goals are to determine the contribution of: 1) specific pathophysiologic pathways; 2) overall health impact of the pandemic; 3) COVID-19 severity, and 4) COVID-19 treatment upon excess new onset diabetes from SARS-CoV-2 infection and response to diabetes therapy. 

Key Dates

Posted Date
July 13, 2022
Open Date (Earliest Submission Date)
November 20, 2022
Letter of Intent Due Date(s)

November 20, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
December 20, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

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.

Expiration Date
December 21, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

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.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement invites multiple Program Director/Prinicipal Investigator (multi-PD/PI) applications to conduct a study to establish a longitudinal cohort of individuals who developed diabetes following SARS-CoV-2 infection to understand the pathophysiology and clinical course post-COVID-19 diabetes. The cohort must include children and adults and reflect the geography and demographics of COVID-19 in the U.S. There must be an appropriate comparator population recruited and followed. The goals are to determine the contribution of: 1) specific pathophysiologic pathways; 2) overall health impact of the pandemic; 3) COVID-19 severity, and 4) COVID-19 treatment upon excess new onset diabetes from SARS-CoV-2 infection and response to diabetes therapy. The NIDDK strongly encourages Research on Sex/Gender Differences, Sexual and Gender Minority-Related Research and Race/Ethnic Diversity (see NOT-DK-22-003). This FOA aligns with the Mission and Vision of the NIDDK Strategic Plan for Research, including the theme of empowering a multidisciplinary workforce, engaging diverse stakeholders, and pursuing pathways to health for all. Specifically, this FOA aligns with the Scientific Goals (1.1 and 1.2) and Cross-cutting Topics (reducing health disparities and increasing health equity among racial and ethnic minority populations and NIH-designated populations that experience health disparities) of the Strategic Plan.

Background

Emerging epidemiologic evidence world-wide suggests worrisome increases in the incidence of diabetes in both adults and children following SARS-CoV-2 infection. Increasing rates have been reported for both type 1 and type 2 diabetes; however, often the type or characteristics of the diabetes have not been well described. Emerging evidence suggests that there may be direct viral-mediated increases in diabetes, given cadaveric studies demonstrating SARS-CoV-2 infection of pancreatic beta cells. Development of hyperglycemia during acute infection could also be due to physiologic stress, systemic inflammation, or COVID-19 treatment, including glucocorticoids. Other pandemic-related factors may be contributing to development of diabetes. For instance, adults and children have gained weight and physical activity has decreased during the pandemic. Rates of poor mental health, including depression, and anxiety have increased. Elevated psychosocial stress is associated with metabolic disease potentially through direct (e.g., elevated systemic inflammation) and indirect mechanisms (e.g., suboptimal lifestyle habits such as sleep and physical activity). Additionally, individuals with post-COVID-19 incident diabetes may have had it previously but have been undiagnosed, been predisposed or at risk to developing diabetes prior to acute COVID-19 and other pandemic insults, and this increased incidence may reflect accelerated onset or an unmasking of pre-diabetes. Many of these indirect pandemic factors are also likely root contributors to racial and ethnic disparities in metabolic health surrounding COVID-19. Research is needed to comprehensively characterize the onset, clinical course, and physiology of new-onset diabetes after COVID-19, and the relationships among predisposing factors, SARS-CoV-2 infection, and diabetes.

Scope

To address this need, this FOA invites investigator-initiated applications to establish a controlled longitudinal observational multi-center clinical study to comprehensively characterize new-onset diabetes and its clinical course following SARS-CoV-2 infection. This study must recruit adults and children with new-onset diabetes observed after SARS-CoV-2 infection and fully characterize the participants metabolically and clinically. Participants with pre-existing undiagnosed diabetes should be excluded. Participants will be followed for 1-2 years to monitor the natural history and characterize the course of diabetes and glycemic response to therapy and assess any potential complications.

The study will recruit adults and children with new-onset diabetes diagnosed following documented SARS-CoV-2 infection. Ideally, participants would be recruited within several months of diabetes diagnosis; however, it is recognized that a longer post-diagnosis period may be necessary with waning COVID-19 rates and may be appropriate if adequate clinical electronic health records (EHR) data can be obtained for the period prior to enrollment. An appropriate comparator group must be included. Participants should be carefully phenotyped and metabolically characterized at enrollment and longitudinally for 1-2 years. Phenotyping should be directed at understanding: 1) the risk factors for diabetes pre and post SARS-CoV-2 infection; 2) whether post-COVID-19 diabetes is reversible or can be reversed; 3) the etiology/diabetes type; 4) temporal relationships between diabetes and COVID-19 clinical course (including severity of COVID-19 (i.e., non-hospitalized, hospitalized, ICU admission, etc.), therapies and other post-acute sequalae of SARS CoV-2 infection (PASC) symptoms); 5) impact of social determinants of health and other pandemic-related social conditions, and 6) responses to diabetes medical treatments.

One award will be made for a multi-center clinical study. The applicant should assemble adequate numbers of collaborators and pediatric and adult recruitment sites. Given the need to rapidly recruit individuals with new-onset diabetes in the context of waning SARS-CoV-2 infections, it is critical to expedite the launch of the study. Therefore, planning prior to application and award is essential, so the study can start quickly once an award is made. Since only one award will be made, each applicant will be expected to assemble a multi-center study with broad demographic and geographic representation . In addition to Clinical Centers (CC), the application should include a Biostatistics Research Center (BRC) that will provide scientific biostatistical input to the design of the study as well as provide coordination and oversight of all recruitment sites (see below). Any required cores (e.g., central laboratory) should also be included. The application is expected to be a multi-PD/PI award between an investigator well versed in clinical research and has documented experience in metabolic investigation in individuals with diabetes (e.g. endocrinologist, diabetologist) and a biostatistician.

Consortium Organization

1. Clinical Centers

The CC will recruit adult and pediatric individuals with new-onset diabetes following SARS-CoV-2 infection and an appropriate comparator group and retain them during the course of the study. The population recruited should have diverse racial and ethnic diversity representation, and it is expected that the overall population recruited by the entire study will reflect the demographic distribution of the U.S. population with COVID-19. Centers must not only have the requisite population from which to recruit but also have proven experience in recruiting and retaining the relevant population of study participants in research studies. The CC will collect data in accordance with established study procedures and submit all samples and data to the BRC, central laboratory and central reading centers, as appropriate and required by the protocol. Investigators at the CC will conduct analyses in conjunction with the BRC investigators. The study group will have exclusive access to data from the study population for a defined period, according to NIDDK and NIH data sharing policies. All study data analyzed for publication of the primary and secondary study outcome(s) are expected to be provided to the NIDDK Central Repository so that it can be shared as appropriate per NIDDK policy and consistent with achieving the goals of the program. The Steering Committee (see below) will establish policies under which ancillary studies may be conducted while the study is ongoing, consistent with applicable laws, regulations, and policies.

2. Biostatistics Research Center (BRC)

The BRC biostatisticians will have worked with the PD/PI and other key investigators to develop the scientific design of the study. The BRC investigators will have primary responsibility for ensuring that the design of the study, including the primary outcome, is scientifically sound and is supported by appropriate power calculations. The BRC will also provide biostatistical and analytic expertise and conduct analysis and interpretation of the laboratory and clinical data in conjunction with investigators at the CC. The BRC will be responsible for guiding development of the statistical analysis plan for the study as a whole and for each manuscript reporting pre-specified primary and secondary outcomes. The BRC will also be responsible for establishing all scientific collaborations for specialized outcomes. The following guidance document describes the potential roles/responsibilities that DK delegates to a BRC: https://www.niddk.nih.gov/research-funding/human-subjects-research/policies-clinical-researchers

In addition to these research functions, the BRC is responsible for the collection, management and analysis of all clinical and laboratory data, including establishment of any central laboratories or cores needed. The BRC will be responsible for ensuring participant confidentiality  and safety, and quality control. The BRC will conduct training and certification of study staff, and maintain and update the protocol and manual of operations. The BRC will oversee implementation of and adherence to the study protocol. The BRC will coordinate communication among and with the CC. The BRC will also be responsible for establishing and maintaining activities related to the single IRB. In addition, the BRC will develop procedures to require study investigators and other relevant personnel associated with the study to identify and manage financial and other conflicts of interest at least annually and share this information with NIDDK staff.

The BRC will coordinate the movement of biologic samples from the CC to a central laboratory and, subsequently, to the NIDDK Central Repository, where samples will be stored for future analyses. The BRC will similarly coordinate with the CC to ensure the flow of other collected data to the appropriate central reading center or core. The BRC will also coordinate work with the NIDDK Central Repository to prepare all study data for eventual archiving and distribution.

The BRC will provide biostatistical, data management and analytic expertise. The BRC will prepare appropriately detailed reports to the Steering Committee and to the Observational Study Monitoring Board (OSMB), which will be appointed by NIDDK, and to the NIDDK staff at regular intervals. The BRC will be responsible for the planning and logistics of meetings of the Steering Committee and its subcommittees, and will assist NIDDK with the logistics for OSMB meetings.

If additional CC are needed to recruit adequate numbers of participants, subcontracts may be added to the award. The BRC will be responsible for recruiting additional CC.

3. Steering Committee

The primary governing body of the study will be the Steering Committee, comprised of the PDs/PIs of the BRC and each CC, and the NIDDK Project Scientist.

The Steering Committee will develop policies and procedures for the study group and ensure that these policies are properly implemented. These may include procedures for modification of study design, use of study samples and data, approval of ancillary studies, publication and presentation of study findings, monitoring study progress, determining completeness and quality of data collection, and other performance measures. NIDDK expects the investigators to develop robust ancillary study policies to provide opportunities for outside investigators to leverage collected data and biospecimens, as well as the recruited cohort, to expand the scientific output of the group.

4. Project Scientist

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

Applications Not Responsive to this FOA

  • This FOA will not support clinical trials. Application for clinical trials are not responsive to the FOA.
  • Single Program Director/Principal Investigator (PD/PI) applications are not responsive to this FOA.
  • Applications lacking a Statistical Analysis Plan are not responsive to this FOA.
  • Applications involving animal or in vitro studies are not responsive to this FOA.

Non-response 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) and the federal requirement for use of a single IRB for cooperative research under 45 CFR 46.114.

Applicants are also encouraged to review NIDDK policies for clinical research and cooperative agreements here: https://www.niddk.nih.gov/research-funding/human-subjects-research/policies-clinical-researchers.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $3.75 million direct costs in Fiscal Year 2023 to fund one award.

Future year amounts will depend on annual appropriations. However, NIDDK intends to award $5 million direct costs in Fiscal Years 2024 and 2025, and $3.75 million total costs in Fiscal Year 2026.

Award Budget

Application budgets to $3.75 million in directs costs for Fiscal Years 2023 and 2026 and $5 million for Fiscal Years 2024 and 2025 are allowed but need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 4 years.

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

Eligible Organizations

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
Foreign Institutions

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. 

Required Registrations

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 full SAM and 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

Multiple Program Directors/Principal Investigators (multi-PD/PIs) are required for this FOA including an investigator well versed in clinical research and has documented experience in metabolic investigation in individuals with diabetes (e.g. endocrinologist, diabetologist) and a biostatistician.

Involvement of a foreign component that includes a foreign cohort needs justification in light of the primary interest being U.S. health. As diabetes care and ability to diagnose diabetes mellitus quickly might differ amongst countries and the pandemic environment itself is so important to this study and will be very dependent on each countries’ policies and access to vaccines and other treatments, a justification is needed to address how the foreign cohort provides information relevant to the U.S. COVID-19 associated new onset diabetes. Important aspects of the foreign cohort to be addressed include social safety net, age, other demographics, vaccine use, COVID-19 treatment as well as other relevant aspects.

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 NIDDK 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: NIDDKletterofintent@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments:

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

The PDs/PIs of the application and every subcontract should provide a letter stating his/her willingness to participate in study activities, including participating in meetings at the NIH and regular conference calls and abiding by approved study policies, and following the common protocol. In the letter, the PD/PI should also discuss past experiences participating in multi-center studies.

In addition, the PDs/PIs and an authorized Institutional Official at every Institution should provide evidence that the Institution is willing to sign a standard reliance agreement and use the single IRB proposed in the application, in accordance with NIH policy on the use of a single Institutional Review Board for multi-site research,https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-076.html.


Statistical Analysis Plan: The filename "Statistical Analysis Plan.pdf" must be used.

The applicant must describe the statistical methods to be used, including the sample size and power calculations, plans for the primary and secondary analyses, and pre-specified interim analyses. This plan is critical to knowing whether applicants have selected the correct cohort size based on proper power calculations and/or are using the most appropriate methods to analyze the resulting data and make correct conclusions at the end of the study. The sample size and statistical power calculations should contain enough detail, including a discussion of assumptions made, so that a reviewer can readily duplicate the sample size projection. The power analysis should include a discussion of the anticipated rates of follow-up (i.e., drop out/lost to follow up) for key outcome measures, regardless of whether they are being collected during research visits, by phone or web-based data.  A discussion of how missing data will be handled should be included. Any planned interim analyses should also be described. The sample size calculations should be based on 90% power. The sample size proposed should be sufficient to detect a clinically meaningful (i.e., not just statistically different) outcomes when determinable, as chosen by the PD/PI.

 Applications that lack the Statistical Analysis Plan are incomplete and will not be peer reviewed.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

The annual budget requested should match the timeline proposed for the project and the scope of the project. It should be understood that, in the event of an award, the budgets at the Clinical Centers may be adjusted during the outyears of the study based on recruitment success. Once the study starts, it is anticipated that there will be two study group meetings in the Bethesda, MD area each year. The budget should also include funding for two Observational Safety Monitoring Board (OSMB) meetings each year. The study should be completed before the end of year 4 to allow ample time for data clean-up and analysis. Funds should also be allocated for the transfer of data (with appropriate documentation) and samples to the NIDDK Central Repository at the end of the award period.

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 clinical study is needed and what evidence gap the study will address, including a discussion of how the results will impact clinical care and/or public health.

The application must include a detailed description for the study design, addressing the scientific rationale for the design chosen, the populations to be studied and the outcomes being assessed. A table should be included showing all outcome measures and the time points for collection. The application should include a discussion of:

  • Inclusion and exclusion criteria, including how long after SARS-CoV-2 infection and/or diabetes diagnosis participants can be enrolled
  • Characterization of COVID-19 disease severity and viral treatment including vaccination status, vaccine type, treatment modalities and virus subtype
  • The comparator group
  • The rationale for all proposed phenotyping/outcomes chosen, as well as frequency of measurement
  • What and how participant level data prior to study enrollment will be obtained that characterizes participant health status prior to study enrollment including the time prior to their SARS-CoV-2 infection
  • What data will be collected to ascertain various type of stress, changes in health-related parameters such as sleep, physical activity and weight, etc., during the pandemic
     

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 study's design must address the adequacy and quality of previous studies.

In addition, the application must address potential biases or challenges in the protocol and how they will be addressed. In particular, what approaches will be implemented to reduce the time between award and study initiation?

Recruitment strategies are encouraged to leverage existing NIH and other sponsored COVID-19 related studies, especially post-acute sequelae of COVID-19 studies. The NIH supports the use of the PhenX ToolKit which includes COVID-19 associated phenotyping tools. Investigators are encouraged to consider utilizing this resource for harmonization of phenotyping in this proposed cohort (https://www.phenxtoolkit.org/covid19).

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • The NIDDK has established a Central Repository 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 other NIDDK-approved repository. The study group will have exclusive access to data for a defined period, according to NIH and NIDDK data sharing policies, https://www.niddk.nih.gov/research-funding/human-subjects-research/policies-clinical-researchers.

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

In addition to the instructions for this section contained in the Human Subject and Clinical Trials Information form, please include a discussion of the availability of potential participants at each proposed study at proposed sites, the anticipated yield from recruitment and screening efforts, and the expected accrual timeline. This study must recruit adults and children with new-onset diabetes observed after SARS-CoV-2 infection and fully characterize the participants metabolically and clinically. The cohort must include children and adults and reflect the geography and demographic of COVID-19 in the U.S.The plan should address specific strategies for recruitment and retention of both children and adults, including efforts to ensure appropriate representation of populations disproportionately affected by both diabetes and COVID-19. Feasibility of identifying potential participants and of recruitment should be addressed in detail. The plan must include a discussion of the applicant’s experience in recruiting and retaining similar populations, expected challenges to recruitment and retention, and possible contingency plans. There must be an appropriate comparator population recruited and followed.

Section 3 - Protection and Monitoring Plans

All parts of Section 3 are required under this FOA.

3.3 Data and Safety Monitoring Plan

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

NIDDK will appoint an Observational Study Monitoring Board (OSMB) for the study.

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 Information form, this should include a description of committee structures needed for study management; and the oversight, responsibilities, and coordination of any sites or cores proposed. The applicant should discuss plans to assure fidelity to the protocol and integrity of the data and policies and methods for ensuring data confidentiality and participant privacy. The PD(s)/PI(s) 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. The applicant should include a discussion of the proposed single IRB, including the experience of the IRB to oversee multi-center studies. The applicant should also describe the process for identification and selection of additional collaborators/Clinical Centers/cores if needed during the study.

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.

 

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" (https://cde.nlm.nih.gov/home) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

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).

Scored Review Criteria

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.

 

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

 

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

Specific to this FOA: How appropriate is the proposed leadership with respect to the scientific expertise of the PD/PI(s) and key personnel to lead the study design, recruitment and retention of children and adults for research, and biostatistics? What expertise do the PD/PI(s) have to organize, manage and implement the proposed clinical study and meet milestones and timelines? How appropriate is the organizational structure? How appropriate is the expertise of the PI/PD(s) and the proposed study team in analyzing and statistically evaluating the proposed outcomes of the clinical study? Do they have the expertise to organize, manage and implement the proposed multi-site clinical study and meet milestones and timelines?

 

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

 

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: How well does the proposed design account for the changing landscape of SARS-Co-V-2 infections? How well does the design appropriately consider both biological and non-biological factors that could contribute to the development of diabetes? How appropriate are measures planned that will accurately ascertain diabetes type? How appropriate is the proposed comparator population? How appropriate are planned analyses and statistical approaches for the proposed study design? How appropriate are the plans to standardize, assure quality of, and monitor adherence to the study protocol and collection of data? How appropriate is the plan to complete data analysis within the proposed period of the award?

 

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

Specific to this FOA: How appropriate is the ability of the proposed sites to: (1) enroll the proposed numbers of an appropriate population; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and (4) operate within the proposed organizational structure?

Additional Review Criteria

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.

   

For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

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

 

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

 

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

 

Not Applicable

 

Not Applicable

 

Not Applicable

Additional Review Considerations

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.

 

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

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

 

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

 

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

 

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK , 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 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 Diabetes and Digestive and Kidney Advisory Council (NDDKAC). 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.
  • Consideration of geographic and racial/ethnic diversity across the Clinical Centers.

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.

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

2. Administrative and National Policy Requirements

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

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 must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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.

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200 and other HHS, PHS, and NIH grant administration policies. The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The Program Director(s)/Principal Investigator(s) will have the primary responsibility for:

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

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

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

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

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

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

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

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

9. Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and network activities that includes access to any network generated resources (i.e., data and biosamples), or study results that are not publicly available, or

using the name of the network or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.

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

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

12. Data Management and Sharing Plan: In accordance with the NIH Policy for Data Management and Sharing (NIH NOT-OD-21-013), the NIDDK approved plan will become a term and condition of award, be routinely monitored during the award period, and compliance may factor into future funding decisions. By the end of the funding or proprietary period, an recipient or study group may not continue to use or share study generated resources until those resources are available to the public via an NIDDK approved repository per the NIDDK approved sharing plan. The NIDDK has established a Central Repository to support the receipt, storage, and distribution of data, biosamples, and other resources generated in clinical studies funded by the NIH/NIDDK. When the NIDDK Central Repository is to be utilized, prior to enrolling participants, the PI or his/her designee will coordinate with the NIDDK Program and Central Repository staff to prepare for eventual archiving and distribution of the study generated resources that are to be maintained in the Central Repository. All resources transferred to the Central Repository will be under the custodianship of the NIDDK. The study’s leadership will have proprietary control of and exclusive access to the resources per the NIDDK approved sharing plan. Subsequently, these resources will be available to the wider scientific community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/ and, https://grants.nih.gov/policy/sharing.htm, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm), as well as the NIDDK policy for resource sharing, NIDDK Data Sharing Policy.

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

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

An NIDDK Project Scientist with substantial involvement will:

1. Serve as the contact point for all facets of the scientific interaction with the recipient (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the recipient on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Project Coordinator, who will provide direct technical assistance to the recipients to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or Project Coordinator will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.

3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.

4. Have substantial involvement assisting in the design and coordination of research activities for recipients as elaborated below:

a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.

b. The NIDDK Project Scientist or Project Coordinator may coordinate activities among recipients by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.

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

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

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

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

2. Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.

3. The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.

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

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

Areas of Joint Responsibility include:

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

Steering Committee

A Steering Committee organized by the study investigator(s) will be the main governing body of the study.

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

The Steering Committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.

A Chairperson will be selected by the Steering Committee. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings and representing the study group by interacting closely with the recipients during protocol development and implementation. The NIDDK Project Scientist may not serve as Chairperson. The NIDDK Program Official shall be consulted regarding the selection of the Chairperson and will have the option to veto the selection based on specific concerns regarding potential for bias or conflict of interest or lack of required expertise. The NIDDK Division of Extramural Activities Director and the Deputy Director of NIDDK will consider the merit of the basis for the veto and the veto shall only be enforced with their concurrence. If either the NIDDK Division of Extramural Activities Director or the Deputy Director of NIDDK have a conflict of interest associated with the decision, then the decision will be made by the individual who is not in conflict in consultation with the NIDDK Director.

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 HHS regulations at 45 CFR Part 16.

3. 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.

Application Submission Contacts

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: http://grants.nih.gov/support/ (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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Saul Malozowski, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-4683
Email: malozowskis@mail.nih.gov
 

Peer Review Contact(s)

Najma Begum, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8894
Email: begumn@nih.gov

Financial/Grants Management Contact(s)

Eunica Haynes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-4018
Email: haynese@mail.nih.gov

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.

Authority and Regulations

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.

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