Part 1. Overview Information

Key Dates

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

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

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

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

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

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Diabetic kidney disease (DKD) imposes the highest social and economic burden among the long-term complications of type 1 diabetes (T1D). Approximately one third of T1D patients develop kidney dysfunction that frequently progresses to end-stage kidney disease (ESKD), requiring dialysis or a kidney transplant for survival. Socially and economically disadvantaged individuals have disproportionately poor outcomes. Unfortunately, progress in the prevention and treatment of T1D nephropathy has remained limited.

Our understanding of T1D nephropathy would significantly improve by identifying key molecular pathways involved in disease etiology and progression.  These pathways could potentially offer insights into unrecognized disease heterogeneity.  The primary limitation to achieving these goals is lack of access to human tissue and the application of state-of-the-art molecular interrogation techniques to such samples. Such interrogation has the potential to also identify specific drug targets and enable individualized care.

This program will leverage and expand on the established Kidney Precision Medicine Project (KPMP).  The KPMP is charged with enrolling adults with acute kidney injury (AKI) and/or chronic kidney disease (CKD) from varied age, sex, racial, ethnic, socioeconomic, and geographic backgrounds into a longitudinal cohort study that includes a research kidney biopsy.  A full description of the scope and organization of KPMP can be found here: https://www.kpmp.org/about-kpmp#background.

There are 4 distinct, but highly interactive activities within KPMP which includes:

1. Recruitment Sites (RS): enroll adults with acute kidney injury (AKI) AKI and/or chronic kidney disease (CKD) from varied age, sex, racial, ethnic, socioeconomic, and geographic backgrounds into a longitudinal cohort study that includes a research kidney biopsy.
2. Central Hub (CH): collect and de-identify all clinical and social risk data and samples, and provide quality control, project management, and administrative support for the entire KPMP.
3. Kidney Tissue Atlas Coordinating Center/Kidney Mapping Atlas Project (KTACC/KMAP): clean, harmonize, store, and curate all de-identified KPMP data, perform integrative analyses, and create an interactive Kidney Tissue Atlas.
4. Tissue Interrogation Sites (TIS): use and develop innovative technologies to analyze human kidney tissue.

The goal of this Notice of Funding Opportunity (NOFO) is to add new recruitment sites (RS) to KPMP that are dedicated to enrolling individuals with, or at high risk of, T1D nephropathy. Both adult and pediatric participants are of interest. These new RS will establish a cohort of individuals with T1D, in order to obtain kidney biopsies and then deeply phenotype participants across multiple domains, including clinical, social determinants of health, and molecular characteristics. These data will be integrated to define sub-phenotypes and identify individual-level candidate treatment targets. Existing KPMP RS are not eligible to apply for this NOFO.

The new RS supported by this NOFO will incorporate into the existing governance structure of the KPMP and be governed by the KPMP Steering Committee (SC) and overseen by two NIDDK-appointed boards: (1) a Data Safety Monitoring Board (DSMB) focused on participant safety, study burden, and the scientific validity of the clinical data, and (2) an Observational Study Monitoring Board (OSMB) focused on the overall scientific progress and direction.

Given the risk of complications from kidney biopsy, the sites funded under this NOFO will prioritize ethical and participant safety considerations. The investigators will work closely with diverse patient partners (e.g., patients serving as study investigators) and research subjects (participants) to ensure their viewpoints, priorities, and preferences inform all aspects of the research.  Participating medical centers will not charge participants for costs associated with kidney biopsies or complications related to research kidney biopsies.

All de-identified data acquired by sites supported by this NOFO will be subject to both KPMP and NIH data sharing policies. The data will be released to the research community immediately upon validation once the risk of explicit or inferred identification has been mitigated. The KPMP Central Hub will house all personally identifiable data (under the control of an Honest Broker), while the KTACC/KMAP will house all de-identified data.

Applicants should carefully review and understand all KPMP policies, as they will also apply to T1D recruitments sites (For Researchers (kpmp.org). Please refer to Other Plan(s) section below.

Applicants should contact NIDDK staff if an application is being considered.

Purpose

This NOFO requests applications for new T1D RS to enroll individuals with, or at high risk for, T1D nephropathy in a longitudinal cohort study that includes a research kidney biopsy. T1D RS will collaborate with KPMP to conduct longitudinal clinical and physiologic phenotyping, capture demographic information, and collect biological samples linked to relevant metadata in accordance with established KPMP protocols (https://www.kpmp.org/for-researchers#protocols). Biopsy protocols and safety criteria will adhere to KPMP protocols.  Inclusion criteria for enrollment and the depth of clinical phenotyping may differ from the current KPMP protocol.  Clinical phenotyping for T1D RS is expected to exceed that of current KPMP RS. Existing KPMP RS may not apply for this NOFO.

Each T1D RS is expected to recruit approximately 15 to 20, or more participants per year, justifying their numbers based on the available disease population and anticipated rate of consent. Each applicant for a T1D RS should demonstrate the ability to identify and enroll the expected number of participants, obtain high-quality research kidney biopsies, ensure safety, minimize risk, and conform to the highest ethical, research, and clinical standards.

Projects proposed in response to this NOFO will require a multidisciplinary team, including nephrologists, endocrinologists, radiologists, pathologists, ethicists, researchers with experience partnering with diverse communities, researchers with expertise in social determinants of health, patient partners (e.g., patients serving as study investigators), and patient advocates.

Research Objectives

Establish a cohort of individuals with T1D and diverse backgrounds with, or at high risk of, T1D nephropathy to obtain research kidney biopsies, biospecimens, social determinants of health, and detailed longitudinal clinical data.

Essential objectives include:

1. Recruitment

• Adhere to the highest ethical principles of clinical research, obtaining informed consent for a research kidney biopsy.
• This may include, but is not limited to:
• Inclusion of pediatric cases is allowed, requiring a careful and detailed description of the approach, case selection, and plan to ensure the highest ethical standards. Applicants should also clearly describe the benefits and scientific justification for including pediatric cases and pediatric research relevant expertise of the investigators.
• The final inclusion and exclusion criteria, and distribution of participants, will be determined by the KPMP SC.
• Biopsy safety-related eligibility criteria have been determined by the KPMP SC, involving participants from all KPMP sites, and are subject to change by the SC based on evolving needs.
• Applicants must indicate their willingness to comply with all SC policies (https://www.kpmp.org/for-researchers), goals, and procedures (https://www.kpmp.org/for-researchers#protocols).
• Applicants must indicate their willingness to follow the final T1D nephropathy study protocol, to be finalized in partnership with the KPMP SC.
• Novel recruitment strategies are encouraged, especially those targeting diverse and underrepresented groups in research.
• Develop contingency plans for unexpected slowdowns or halts in recruitment, including plans for continued longitudinal follow-up of existing participants and re-starting recruitment.
• Include co-investigators knowledgeable and skilled in kidney biopsy. These individuals should have an exceptional safety record and provide statistics regarding complications from kidney biopsies they have performed.
• Enlist local involvement of patients, practitioners, and ethicists to enhance safe and acceptable procedures for performing research kidney biopsies.
• Demonstrate the ability to obtain consent for genetic studies and re-consent for additional longitudinal data and biosample collection, and potential repeat biopsies.
• Enrollment of individuals who have participated in prior studies or are part of registries where prior clinical data and/or biospecimens are available is strongly encouraged.
• Obtain comprehensive kidney function assessment. Considerations for renal physiologic measures to capture various renal function domains beyond glomerular filtrations measures, is required. Potential measures of interest include measures of renal reserve, tubular function such as physiologic stress tests, and functional imaging. 
• It expected that the clinical phenotyping proposed and performed by the T1D RS will surpass that of current KPMP RS (Available Data (kpmp.org). These enhancements may include, but are not limited to:
• Individuals at high risk of nephropathy: Various metrics may determine high risk, such as evidence of hyperfiltration (e.g., history of increasing eGFR or high age-adjusted eGFR), multiple risk factors (e.g., poor glycemic control, hypertension), and/or investigator proposed risk/injury biomarkers.
• Individuals with evidence of early nephropathy: This group might include those with eGFR < 90 and ? 60 ml/min/1.73m² and/or albuminuria.
• Individuals with established CKD: This group includes those with eGFR < 60 ml/min/1.73m² but ? 30 ml/min/1.73m².
• Individuals with renal resilience: This groups includes those with longstanding T1D (e.g., greater than 15 years) and no evidence of nephropathy.
• Detailed retinal imaging measures such as optical coherence tomography with angiography.
• Measures of cardiovascular disease (CVD) or function, including measures of CVD with sufficient sensitivity in individuals with early/subclinical CVD disease.
• Obtain longitudinal follow up, including yearly in-person visits, validated questionnaires pertaining to social determinants of health, clinical variables, detailed glucose monitoring (i.e., CGM), medications, and outcomes. Consider enrichment of phenotyping and outcome data collection via home and electronic-based follow-up and EHR data capture.
• Apply extensive application of longitudinal blood and urine based multi-omics and biomarker-based measures. Match the existing KPMP coverage (e.g., genetic sequencing, transcriptomic, proteomic, and metabolomic). Coordinate these efforts with KPMP Central Hub and KTACC/KMAP to ensure the use of the same platforms and QA/QC measures. Consider repeat testing to assess changes over time, as well as additional measures not covered under the current KPMP protocol. Applicants must budget for the blood and urine based multi-omic measures. KTACC/KMAP will oversee the implementation of biopsy tissue processing and interrogation via the TIS (i.e., applicants need not to plan directly nor budget for TIS activities).

Collaboration and Sharing

• Work collaboratively as a member of the KPMP SC to identify important scientific questions, adapt to new findings, and update protocols as appropriate to ensure completion of the study goals and participant safety.
• Apply common study protocols for data collection, written informed consent, performance of research kidney biopsies (including specialized training for the performance of research biopsies), and for tissue handling, processing, and shipping.
• Contribute to the development of a KPMP-wide quality management plan (led by the Central Hub) that spans every step of the project (including clinical phenotyping, tissue/sample collection, handling, processing, transportation, interrogation, analysis, and visualization).
• Participate in working groups and sub-committees as an active member of the KPMP community.
• Submit all data, metadata, protocols, and biosamples to the Central Hub. In general, the Central Hub will house all personally identifiable data (under the control of an Honest Broker), while the KTACC/KMAP will house all de-identified data.
• Ensure participant re-identification risk is minimized.
• Submit all tissue blocks, routine clinical pathologic slides, and clinical pathology reports to the Central Hub. The KPMP will perform conventional and advanced (e.g., omic, 3-Dimensional imaging) pathologic reading of all available tissue and compare to the clinical diagnosis and local site pathologic analyses. It is expected that the Central Hub will house the clinical data and sample repository, while the KTACC/KMAP will maintain a digital pathology bank of all existing and new whole slide images.

B.  Utilization of the KPMP state-of-the-art tissue interrogation resources and expertise (e.g., coordinated single cell level transcriptomic, proteomic, metabolomic including spatial analyses). This will allow the investigative community to optimally leverage precious and limited renal biopsy tissue to facilitate discovery of T1D nephropathy specific molecular pathways, subgroups and identify candidate novel therapeutic targets. Tissue analyses will be performed by KTACC/KMAP and do not need to be directly addressed or budgeted for in this application.
 

Expected outcomes from the project period will be:

• Recruit, consent, and complete research kidney biopsy on 15 to 20 or more diverse participants per year, meeting recruitment goals, while ensuring participant safety and minimizing complications of biopsy.
• Obtain fully informed consent of participants for enrollment, kidney biopsy, follow-up, recontact, and reconsent (e.g., repeat biopsy)
• Conduct longitudinal clinical phenotyping, capture demographic information, and collect biological samples and metadata in concordance with finalized T1D nephropathy protocol.
• Monitor QA/QC of all processes, data, and samples.
• Ensure participant re-identification risk is minimized.
• Work collaboratively with the KPMP investigators and adhere to all KPMP and NIH data sharing policies. 
• Implement and strictly adhere to FAIR data (Findable, Accessible, Interoperable, and Reusable) principles.
• Contribute to the scientific output of the KPMP.

This NOFO is not intended to support hypothesis testing. Applications including animal studies are not responsive and will be withdrawn.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019, and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - 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 How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

Letter of support: A letter of support from the institution acknowledging the cost of $3,500 per research kidney biopsy, which has been agreed upon by the KPMP and their respective institutions, is required. The Letter of support should be signed by a business official on organization letterhead. 

Statement of willingness: The filename "Willingness Statement.pdf" should be used. The statement should be signed by a business official on organization letterhead and should attest to the following:

• The awardees will agree to be governed by the KPMP (cite) and adhere to all established policies and procedures of the KPMP consortium.
• Key personnel will attend the launch meeting September 30 to October 1, 2025 in Bethesda MD/Washington DC.
• The study investigators will cooperatively interact with the NIDDK in support of the KPMP. The institution will ensure participants and/or their insurance company(s) will not be charged for costs associated with medical care to treat complications related to research kidney biopsies.
• The study investigators will actively seek input from the NIDDK regarding resource or expertise needs.
• The study investigators will make available to the KPMP any preliminary data included in this application upon award.
• The study investigators will work collaboratively with other KPMP investigators on weekly/monthly conference calls, Working Groups, SC meetings, and in the dissemination of research findings consistent with all Publications and Presentations (P&P) policies (as determined by the SC).
• The study investigators will accept common protocols (https://www.kpmp.org/for-researchers#protocols ) and agreements (https://www.kpmp.org/for-researchers ) developed by the KPMP.
• The institution will rely on the KPMP single Institutional Review Board (sIRB) selected by the KPMP Central Hub.
• The institution and the study investigators will sign the KPMP Confidential Disclosure Agreement (CDA, https://drive.google.com/file/d/1VfTWMXus2c51R5c9L2sBZ-5mu67mUEXy/view and Material/Data Transfer Agreement (MTA,https://drive.google.com/file/d/1NJMhDkIChP4XI3kMq9bCFeS1pYj1m2f9/view) documents. No edits to either the CDA or MTA will be allowed.
• The institution will allow the CH institutional representatives to centrally manage negotiations with industry and external partners in academia and nonprofit institutions on behalf of the consortium, including this T1D RS.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

A key individual (Pathologist) with expertise to support feature scoring and adjudication of biopsies should be included.

R&R or Modular Budget

All instructions in the How to Apply - Application Guide must be followed.

• A cost of $3,500 per research kidney biopsy has been agreed upon by the KPMP and their respective institutions. A letter of support from the institution acknowledging this cost is required. 
• Minimum Effort
  • PD(s)/PI(s) will be required to declare a minimum effort of 2.4 person-months (20 percent) effort per year.
  • Applications proposing Multiple PD(s)/PIs(s) must have a minimum combined PD/PI effort of 2.4 person-months. 
• Interrogation of biopsy tissue will be performed by the TIS and do not need to be budgeted for in this application.
• Applicants should include sufficient pathologist effort to allow for adjudication of biopsies and participation in other relevant KPMP activities. Applicants should include sufficient research coordinator(s) effort for IRB submission of protocol/consent forms, training, and implementation of the protocol for longitudinal follow up of the cohort participants.
• Applicants should arrange logistical services for protocol-specific costs, including subcontracts and supplies.
• Applicants should include support for the activities as member(s) of the SC, including in-person travel to Bethesda MD/Washington DC at least two times per year throughout the project period, including the launch meeting anticipated for September 30 to October 1, 2025. This should include the travel, lodging and per diem costs of patient partners to attend face-to-face meetings of the SC. 

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Applicants should propose to recruit diverse (with regards to sex, age, race, ethnicity, socioeconomic and geographic backgrounds) individuals with T1D with, or at high risk of, T1D nephropathy, for a longitudinal cohort study that includes a research kidney biopsy. Proposals including adult and/or pediatric participants will be considered.

Research Strategy: Organize the Research Strategy in the subsections identified below.

1) Background and Significance

• Applicants should identify as an adult site or a site that will recruit adults and children. Provide the number of expected biopsies for proposed recruitment groups.
• Applicants should discuss ethical and safety issues in obtaining a research kidney biopsy in participants with T1D. If applicable, additional discussion and ethical considerations for proposed inclusion of children should be clearly presented.
• Applicants should discuss the scientific questions that need to be addressed from the longitudinal cohort, in particular, the objective to define disease heterogeneity and determine the precise molecular pathways that will facilitate identification of specific drug targets and ultimately enable individualized care for people with T1D.
• Applicants should discuss challenges in obtaining research kidney biopsies and performing longitudinal follow-up in the proposed recruitment population with T1D.

2) Preliminary Data

• Applicants should demonstrate that the site has the experience and capacity to ensure safety, minimize risk, and conform to the highest ethical, research and clinical standards. Applicants should describe how both patient participant and physician attitudes, opinions, and beliefs about the acceptability of kidney biopsies for research will be considered. This will likely involve a diverse and multidisciplinary team of nephrology, endocrinology, radiology physicians, ethicists, members of IRBs and patient partners.
• Applicants should engage local patient partners and representatives from diverse backgrounds to provide advice to site researchers on approaches to educate participants about the need for research kidney biopsies and obtain informed consent. Demonstrate knowledge and understanding of the ethical issues involved in obtaining informed consent to collect kidney biopsy tissue for research purposes, especially from T1D participants who have not been traditionally biopsied.
• Applicants should demonstrate pre-application involvement by the local IRB, for a study in which kidney biopsy tissue is collected for research. A letter from the local IRB should be included in the application indicating their willingness to rely on the KPMP single IRB.
• Applicants should document the number of clinical and research kidney biopsies performed previously and provide statistics regarding complications.

3) Approach

• Applicants should propose and justify an approach to study patients with, or at high risk for, T1D nephropathy over the five-year project period specified in this NOFO. All sites are expected to recruit approximately 15 to 20 or more participants per year and justify their numbers based on available disease population and anticipated rate of consent.
• Applicants should demonstrate that the site can ethically recruit participants; obtain high-quality research kidney biopsies while conforming to the highest ethical, research and clinical standards. Individuals performing kidney biopsies should have an exceptional safety record and provide statistics regarding complications.
• Applicants should document the clinical and research experience of the team in recruitment, retention and other key areas related to the study.
• Applicants should demonstrate an understanding of current KPMP protocols and their ability to consent and (re) consent, recruit and retain participants. Applicants should demonstrate the ability to adhere and comply with all relevant aspects of the current KPMP protocols and demonstrate flexibility to adapt to changing protocols over time.
• Applicants should demonstrate their ability and willingness to participate in a Precision Medicine for T1D nephropathy focused working group. The T1D working group will focus on the development of clinical phenotyping as well as inclusion and exclusion criteria that are specific to theT1D nephropathy study (i.e., distinct from KPMP). The T1D working group may not supersede the KPMP SC and its oversight committees (e.g., KPMP DSMB and OSMB).
• Details of potential enrollment of participants engaged in prior studies or collaborations with other longitudinal cohort studies or other subcontracted sites should be provided. Backup recruitment plans and efficient use of EHRs for recruitment are encouraged.
• Applicants should describe contingency plans for an unexpected slowdown or halt in recruitment (e.g., pandemic-associated research restrictions), including plans for continued longitudinal follow-up of existing participants and re-start.
• Applicants should discuss plans to ensure appropriate diversity (sex, age, race, ethnicity, socioeconomic and geographic backgrounds) of participants. Identify and promote best practices to ensure equitable engagement of participants from representative racial and ethnic groups.
• Applicants should discuss plans to ensure the capture of data that measures social determinants of health to assess social risk of participants (e.g., socioeconomic status, food insecurity, residential segregation, perceived discrimination, measures of stress/allostatic load).
• Complete longitudinal follow-up of participants will be necessary to avoid bias. Applicants should discuss how participants will be followed. Demonstrate your ability to collect longitudinal data, including follow-up visits and biosample collections. Efficient use of EHRs for follow-up is encouraged.
• Applicants should discuss details of transmission of study data/metadata and transport of all biosamples to the Central Hub. It is expected the Central Hub will house personally identifiable clinical data (under the control of an Honest Broker) and the sample repository.
• Applicants will also need to discuss arrangement with the KPMP KTACC/KMAP, which will maintain a de-identified digital pathology bank of all existing and new whole slide images. All applicants will need to have a clear understanding of the KPMP protocols by discussing them with the KPMP Central Hub and KTACC/KMAP. Additional information and full protocols are also available online:  https://www.kpmp.org/for-researchers. Complete Manual of Operations can be seen online at: KPMP_Recruitment-Site-MOP.pdf - Google Drive
• Applicants should propose consent for genetic studies and potential (re)consent for additional longitudinal data and biosamples collections.
• Applicants should discuss the ethics and feasibility of repeat biopsies.
• Applicants should describe the pace of enrollment, consent, research biopsy, and sample/data collection with careful attention to participant safety, retention, and quality metrics.

4) Milestones and Timelines

• Applicants should provide a timeline and milestones. Milestones are objectives that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Milestones should function as indicators of continued progress, thus revealing emergent difficulties, and will be used to evaluate the application not only in peer review, but also when considering the awarded project for funding of non-competing award years. Timelines must state when metrics for assessment of progress will be achieved.
• Applicants should include a timeline for T1D participant recruitment initiation and recruitment target milestones.
• Applicants should provide appropriately detailed (quantitative) criteria by which milestone achievement will be assessed.
• Applicants should provide a detailed timeline for the anticipated attainment of each milestone and the overall objective.
• Applicants should identify any impediments that could require modification to the research plan, milestones, and/or timeline with a discussion of alternative approaches.

5) Activities and Management of the Multidisciplinary Team

• The multidisciplinary team of investigators should include nephrologists, endocrinologists, physicians, pathologists, radiologists, ethicists, researchers with experience partnering with diverse communities, researchers with expertise in social determinants of health, patient participants, and, if applicable to the proposed project, pediatric expertise.
• Applicants should clearly describe the formal organizational structure of the multidisciplinary team, including lines of authority and responsibility, with attention to the relationship of the organizational structure to the major objectives of the KPMP.
• Applicants should document the collaborative nature of the research team and emphasize the qualifications, past performance, and experience of the key personnel, particularly working on actively managed, milestone-driven projects.
• Applicants should discuss how the diverse expertise of the team members increases the capability for innovation, the ability to anticipate new directions, and the flexibility to redirect research when needed.
• Applicants should describe training, procedures, and experience necessary to safely obtain usable tissue from a kidney biopsy from patient participants with and/or at high risk of T1D nephropathy. It is expected that biopsies will be in individuals representing the full spectrum of T1D nephropathy (e.g., renal resilient, at high risk, early stage, established).
• Applicants should document the clinical and research experience of the team in recruitment, retention and other key areas related to kidney biopsy studies. Individuals performing kidney biopsies should have an exceptional safety record and provide statistics regarding complications.
• Applicants should discuss how the site will promote active participation in all relevant T1D nephropathy and KPMP activities and working groups.
• Applicants should confirm willingness to share all data, metadata, and samples, including tissue blocks, routine clinical pathologic slides, and reports, and discuss how they will be harmonized with ongoing and new efforts. It is expected that the Central Hub will coordinate a repository for all biosamples and study defined personally identifiable data (under the control of an Honest Broker). It is expected that the KTACC/KMAP will house all de-identified data, which may also be housed by the NIDDK Central Repository.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

The following modifications also apply:

The NIDDK intends the resource sharing plans for the samples generated under the KPMP to follow the policy and objectives stated in the original KPMP NOFOs. Specifically, consistent with achieving the objectives of the KPMP, all study  protocols (including analytical methods), ontologies, technologies, biological samples (including but not limited to biopsies, nephrectomy tissue, tissue blocks, all slides in any form, blood, urine and stool) and other research resources are to be shared immediately across the consortium, and made publicly available to the larger community as soon as QA/QC procedures have been completed, and in accordance with KPMP SC policies, subject to approval by the NIDDK.  Limited exceptions to the requirement for community dissemination may be identified by the KPMP SC and are subject to approval by the NIDDK. The NIDDK, in consultation with the SC for this project, will make all final decisions concerning sample deposition and all policies are subject to change by the NIDDK as deemed necessary to sustain program principles and priorities, or to ensure the highest standards for responsible research conduct within the project.

• Awardees will comply with and implement the recommendations and decisions of the KPMP SC with respect to the sharing of information, biosamples, protocols, resources, methods, and analyses developed by the KPMP investigators under the KPMP.
• Awardees will comply with the KPMP agreements including the Publications and Presentations (P&P) policies (as determined by the SC). Participating Institution(s) must sign the KPMP Confidential Disclosure Agreement (CDA, https://drive.google.com/file/d/1VfTWMXus2c51R5c9L2sBZ-5mu67mUEXy/view (https://drive.google.com/file/d/1VfTWMXus2c51R5c9L2sBZ-5mu67mUEXy/view)) and Material Transfer Agreement (MTA, https://drive.google.com/file/d/1NJMhDkIChP4XI3kMq9bCFeS1pYj1m2f9/view
• (https://drive.google.com/file/d/1NJMhDkIChP4XI3kMq9bCFeS1pYj1m2f9/view)) documents. No edits to either the CDA or MTA will be allowed.

Other Plan(s): 

All instructions in the How to Apply - 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 How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

Delayed Onset Study

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

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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

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

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute of Diabetes and Digestive and Kidney Diseases (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 (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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

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.

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 (NIDDK), in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

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

Applications will be assigned 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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

TERMS AND CONDITIONS OF COOPERATIVE AGREEMENT AWARDS RESEARCH PROJECT APPLICATIONS FOR NON-CLINICAL STUDIES

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and 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.

This program will leverage and expand on the established Kidney Precision Medicine Project (KPMP).  The KPMP is charged with enrolling adults with acute kidney injury (AKI) and/or chronic kidney disease (CKD) from varied age, sex, racial, ethnic, socioeconomic, and geographic backgrounds into a longitudinal cohort study that includes a research kidney biopsy.  A full description of the scope and organization of KPMP can be found here: https://www.kpmp.org/about-kpmp#background.

The PD(s)/PI(s) will have the primary responsibility for:

• Recipient(s) will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award. 
• The Program Director/Principal Investigator (PD/PI) will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement (NOFO) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• Recipient(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.
• Recipients are responsible for their staff in maintaining confidentiality of the information as developed by the network/consortium, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the Steering Committee (SC) as well as any confidential information received by third party collaborators.
• Recipients must analyze, publish and/or publicly release and disseminate results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and achieving the goals of the NOFO.
• Data Management and Sharing Plan: In accordance with the NIH Policy for Data Management and Sharing (NIH NOT-OD-21-013), the NIDDK approved plan will become a term and condition of award, be routinely monitored during the award period, and compliance may factor into future funding decisions. By the end of the funding or proprietary period, a recipient or study group may not continue to exclusively use or share study generated resources until those resources are available to the public via a NIDDK approved repository per the NIDDK approved plan.
• Recipient(s) will be required to participate in a cooperative and interactive manner with members of the network/consortium including designated NIH staff (e.g., Program Official, Project Scientist, Project Coordinator).
• Recipient(s) agree to establish agreements amongst themselves that address the following issues: (1) procedures for data sharing among network/consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the network/consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing bio-specimens under an overarching Material Transfer Agreement (MTA) amongst network/consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• 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, applicable network/consortium policies, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network/consortium studies between grantee and third-party will be provided to the NIDDK Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network/consortium policies. Further, at the request of the NIDDK Program staff, any other network/consortium-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: “Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions)”, and Section 8.5.2, titled: “Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support”, noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.”
• Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and network/consortium activities that includes access to any network/consortium generated resources (i.e., data and biosamples), or study results that are not publicly available, or using the name of the network/consortium or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.
• Recipients must agree to comply with the processes and goals as delineated within the NOFO.
• Recipient(s) agree to the governance of the study through a Steering Committee:
  • The PD/PI, or contact PD/PI in the case of multi-PD/PI awards, will serve as a voting member of the Steering Committee and will attend all meetings of the Steering Committee.
  • Each full member will have one vote.
  • The Recipient will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and subcommittees.
  • Recipients must serve on Subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator’s Retreat.
  • Recipients must share data, materials, models, methods, information and unique research resources that are generated by the projects in concordance with Network/Consortium policies in order to facilitate progress. When appropriate, and in accordance with NIH policies, as well as NIDDK policies, Recipients will be expected to collaborate; share novel reagents, biomaterials, methods and models and resources; and share both positive and negative results that would help guide the research activities of other members.
  • Upon completion or termination of the research project(s), the Recipients are responsible for making all study materials and procedures broadly available (e.g., putting them into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making all study materials and procedures available to the scientific community and the NIH for the conduct of research. The Data Management and Sharing Plan should include a plan to accomplish aforementioned at the end of the study.
  • Recipients may be asked to scientifically review applications for special opportunity pool funds, as it is deemed appropriate.

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

The NIDDK will designate program staff, including a Program Official and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award (NOA).

An NIH IC Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows:

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.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist 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 ensure 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) participant 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.
6. The NIDDK may invite External Consultants [External Experts] with relevant scientific expertise for the sole purpose of consultative advice on scientific developments and opportunities that may enhance the achievement of the study goals.
7. The NIDDK Project Scientist(s), Project Coordinator, and Program Official will review and approve applications of the Special Opportunity Funds to ensure that they are within the scope of network/consortium research as described in the NOFO and NIH guidelines.

Areas of Joint Responsibility include:

Through the Recipient, Steering Committee and NIH staff, the study members will cooperatively develop and implement processes to submit information and data to the Coordinating Center (CC), determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the study, consistent with NIH policies and achieving the goals of the program as described in the NOFO.

• Steering Committee (SC)

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-investigator(s) as deemed necessary, and the NIDDK Project Scientist.  The final structure of the Steering Committee and voting procedures will be established at the first meeting.  The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees.  The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.  The NIDDK Program Official may serve as a non-voting member on the Steering Committee.

A Chairperson of the Steering Committee will be selected and voted on by the Steering Committee members.  The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings and by interacting closely with the recipients during protocol development and implementation.  The NIDDK Project Scientist may not serve as Chairperson.  The NIDDK program official will review the Committee’s selection for potential bias, conflicts of interest, or lack of required expertise. If the Program Official has concerns regarding selection of the Chairperson which are not satisfactorily resolved, the Program Official may withhold concurrence if approved by the Director, Division of Extramural Activities, NIDDK based on written justification.  In cases where Program Official concurrence is withheld, the Steering Committee will be required to make another selection. 

External Consultants

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

Dispute Resolution:

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

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

?    The NIH intends the sharing plans for the data generated under the KPMP to follow the policy and objectives stated in the NOFO. Specifically, consistent with achieving the objectives of the KPMP, all study data (including, but not limited to, raw data, metadata, digital pathology images, and computational data sets) are to be shared immediately across the consortium, and made publicly available to the larger community as soon as quality control procedures have been completed, and in accordance with KPMP SC policies, subject to approval by the NIDDK. Data derived from participant clinical records linked to biological data will only be made publicly available once risk of explicit or inferred identification has been mitigated in consultation with the Community Engagement Committee and the DSMB. Limited exceptions to the requirement for community dissemination may be identified by the KPMP SC and are subject to approval by the NIDDK. The NIDDK, in consultation with the SC for this project, will make all final decisions concerning data deposition and data access policies, and all policies are subject to change by the NIH as deemed necessary to sustain program principles and priorities, or to ensure the highest standards for responsible research conduct within the project.
?    Awardees will comply with and implement the recommendations and decisions of the SC with respect to the sharing of data developed by the KPMP investigators under the KPMP.
?    This plan should also address methods for continuing to make the KPMP data available to the NIH and the research community upon completion of studies or termination of the site so that accumulated data remain accessible, for example, through the NIDDK Central Repositories.
 

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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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

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

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

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

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]

Afshin Parsa, MD, MPH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-1375
Email: [email protected]

Ivonne Schulman, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-3350
Email: [email protected] 

Ryan Morris, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-480-1296
Email: [email protected]

Diana Ly
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-9249
Email: [email protected]

Section VIII. Other Information

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

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