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)

National Institute of Environmental Health Sciences (NIEHS)

Funding Opportunity Title
Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium – Renal Science Core (U01 - Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices
  • August 28, 2020 - Notice of Correction to Eligibility in NIH Funding Opportunity Announcements. See Notice NOT-OD-20-171.
  • August 20, 2020 - Notice of Revision to Funding Opportunity Description for RFA-DK-20-018. See Notice NOT-DK-20-042.
  • July 29, 2020 - Notice of Pre-Application Webinar for the Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium. See Notice NOT-DK-20-037.
Funding Opportunity Announcement (FOA) Number
RFA-DK-20-018
Companion Funding Opportunity

 

RFA-DK-20-017, U01 Research Project - Cooperative Agreements,
RFA-DK-20-019, U24 Resource-Related Research Projects - Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.847, 93.113

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites applications for a Renal Science Core (RSC) to support and provide scientific guidance as part of a new consortium to study Chronic Kidney Disease of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE). The RSC will provide scientific expertise in planning clinical phenotyping and measures of renal function; will guide strategies for biological sampling and handling; and will provide needed clinical laboratory based measures and renal pathology. The RSC will also provide renal pathophysiologic expertise to propose approaches, novel measures (e.g., omics and molecular markers) and interpret discovery science to elucidate the cause or causes of CKDu.

This collaborative research consortium will bring together a broad range of expertise and enable discovery science to understand the cause or causes of CKDu and disease progression. The Consortium will also work to identify potential therapeutic targets and public health interventions. The Consortium will consist of a Scientific Data Coordinating Center (SDCC), Field Epidemiology Sites (FES), a Renal Science Core (RSC), and the Human Health Exposure Analysis Resource (HHEAR). The Consortium will work together to finalize ethical epidemiology research designs, execute common strategies for biological sampling and environmental assessment, apply the best analytic strategies for collected samples and data, and disseminate results to the global research and public health communities. The final design of the study, as determined by the Steering Committee, may significantly vary from individual applications. It is required that all funded sites fully abide with the final harmonized design set by the Consortium Steering Committee.

This FOA will not support clinical trial or intervention trials. This FOA is intended to support only human studies; applications that include animal or model systems are not responsive.

Key Dates

Posted Date
July 24, 2020
Open Date (Earliest Submission Date)
October 10, 2020
Letter of Intent Due Date(s)

October 10, 2020

Application Due Date(s)

November 10, 2020

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2021

Advisory Council Review

May 2021

Earliest Start Date

July 2021

Expiration Date
November 11, 2020
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

The Renal Science Core (RSC) will be part of a new consortium to study Chronic Kidney Disease of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE). The Consortium will also include a Scientific Data Coordinating Center, Field Epidemiology Sites, and the NIEHS Human Health Exposure Analysis Resource (HHEAR). The Consortium will work together to enable discovery science to understand the etiology of CKDu, and potential therapeutic targets and public health interventions. The consortium will develop common protocols for evaluation of participants who are currently affected with early manifestations of CKDu and appropriate unaffected control participants, to define common strategies for biological sampling and environmental exposure assessment, and to determine analytic strategies to best use the samples collected by the Consortium. This consortium is also intended to serve as a resource for ancillary studies testing hypotheses pertaining to the development, progression, prevention and/or treatment of CKDu.

Background

Chronic Kidney Disease of uncertain etiology (CKDu, also known as Mesoamerican Nephropathy, Chronic Interstitial Nephritis of Agricultural Communities, and Kidney Disease of Unknown Cause in Agricultural Laborers), reflects a pattern of endemic kidney diseases described as progressively declining glomerular filtration rate (GFR) with no or mild proteinuria, and typically the absence of usual risk factors for Chronic Kidney Disease (CKD) (e.g., hypertension, diabetes, or immune-mediated glomerular disease). Clinical characteristics and available kidney biopsies suggest a primarily tubulo-interstitial disease, rather than a glomerular process. The disease has been reported most consistently among young male agricultural workers in hot humid regions, primarily Mesoamerica, Sri Lanka, and India. There are also reports of familial clustering. The etiologies of CKDu are unclear, but could involve a complex interplay of environmental exposures, genetic variation, infections, and/or lifestyle factors. For example, specific genetic variants may contribute to increased susceptibility and/or predispose to more severe disease progression. Exposures such as nephrotoxicant chemicals, herbal or prescription medication use, infectious agents, lifestyle factors such as alcohol consumption or tobacco use, or occupational conditions such as heat, workload, and dehydration may influence susceptibility to CKDu independently or in combination with other factors.

For the purposes of this consortium, individuals with presumed CKDu are initially defined as:

  • Participants age 18-45 years
  • Serum creatinine concentration >1.2 mg/dl (females) or >1.5 mg/dl (males)
  • Urinalysis = 2+ protein, = 1+ hematuria
  • Residing in a CKDu-endemic community or region

The final definition and selection of cases and controls will be based on deliberations by the full CURE Consortium, once it is formed.

Consortium Structure

The CURE consortium will be formed to respond to this devastating epidemic of kidney failure. Its structure will consist of a Scientific Data Coordinating Center (SDCC), Field Epidemiology Sites (FES), the Renal Science Core (RSC), and the Human Health Exposure Analysis Resource (HHEAR).

  • The SDCC will lead the Consortium in the development and successful execution of the study designs and protocols. The SDCC will review, coordinate and integrate the study protocols from the FES, the RSC, and their own proposed study design, and will lead the Consortium as it develops and implements a harmonized, study-wide protocol reflecting the scientific goals of the FOA. The SDCC will be responsible for the development of data collection tools, data management and statistical analysis strategies as well as overall project management. The SDCC will maintain a temporary biorepository and arrange sample shipping and storage from the FES to the RSC and to HHEAR laboratories.
  • The FES will conduct the field epidemiology of the Consortium. The FES will identify, recruit, enroll, and follow study participants in CKDu-endemic regions, including individuals with evidence of CKDu and appropriate controls. The FES will complete clinical assessments and collect data, biological samples (including blood, urine, and other matrices), and environmental samples over multiple visits. Where safe and feasible, the FES will perform kidney biopsies in a selected subset of participants with CKDu. Biological and environmental samples will be sent from the FES to the SDCC for distribution to the RSC and to HHEAR. Following final consortium-wide protocols, the FES will collect data on relevant risk factors and covariates including environmental and occupational exposures and will review data with the SDCC. The FES will also facilitate the return of results to study participants where agreed upon by the Consortium Steering Committee and local ethical review boards.
  • The RSC will provide scientific expertise in planning, clinical phenotyping, and measures of renal function, which will be collected at the FES. The RSC will guide strategies for biological sampling and handling, and will provide needed clinical laboratory-based measures and renal pathology. The RSC will also provide renal pathophysiologic expertise to propose approaches, novel measures (e.g., omics and molecular markers) and interpret discovery science to elucidate the cause or causes of CKDu.
  • The HHEAR will provide scientific expertise in environmental health and will perform the exposure analyses for the Consortium. HHEAR is an existing NIH-funded resource with high quality exposure assessment services for biological and environmental samples (https://hhearprogram.org/). HHEAR will advise the Consortium on targeted and untargeted analyses of environmental exposures and guide the FES and SDCC on methods for sample collection, shipment, and storage. Potential targeted analyses (https://hhearprogram.org/sample-matrix-table) may include markers of exposure to polycyclic aromatic hydrocarbons, inflammation, trace elements, nutrients, pesticides, pharmaceuticals, or other analytes. Untargeted analyses may be used to examine large sets of analytes through hypothesis-free approaches. HHEAR will also work with the SDCC to integrate environmental data with other Consortium data and provide statistical consultation for environmental data analysis.

Steering Committee

The CURE Steering Committee (SC) will consist of Program Directors/Principal Investigators (PDs/PIs) from each FES, RSC, SDCC, HHEAR, and the NIH project scientists. The SC will hold regular meetings as determined by needs of the Consortium. It will designate subgroups and working groups and all PDs/PIs are expected to participate actively in these groups. The Steering Committee will serve as the governing body of the Consortium and will vote to accept the final protocol and other actions pertaining to the governance, design and implementations of matters pertaining to the Consortium and the successful achievement of the goals of the FOA (see section VI, #2, Cooperative Agreement Terms and Conditions of Award—Areas of Joint responsibility).

 

Renal Science Core (RSC)

The RSC will serve the Consortium by providing relevant measures of renal function for participants and controls enrolled in the epidemiologic study of CKDu designed by the full Consortium. The RSC will propose, facilitate and oversee the biological sampling and clinical phenotyping strategies which will be carried out by the FES. The RSC will also provide renal pathophysiologic expertise to propose and interpret discovery science to elucidate the cause or causes of CKDu. It is anticipated the study will include approximately 1200 participants affected by CKDu and an equal or greater number of control participants. The RSC will also propose a discovery science plan to understanding CKDu and provide state-of-the-art laboratory assays, which can include molecular markers and omics, to address potential etiologies and mechanisms of disease, likely in conjunction with HHEAR laboratories.

It is anticipated that the RSC research plan may not be solely hypothesis-driven and that a combination of state-of-the-art assays, spanning -omic or “discovery” tools to targeted assays, may be well-justified.

Applicants to this FOA should have well-documented expertise in state-of-the-art methods that can be used or adapted to interrogate human biological samples (e.g. blood, urine, and kidney tissue). The RSC must incorporate expertise in kidney research, pathology, quality control and quality assurance and, as needed, may also include members with demonstrated expertise in biomarker discovery, genomics, proteomics, metabolomics and relevant analytic strategies. Multi-PI applications are strongly encouraged.

Applicants must cooperate with the SDCC in managing material transfer agreements and data use agreements. Applicants must be willing to work with HHEAR laboratories to share biological samples for environmental exposure analysis.

Research Objectives

The Renal Science Core will:

  • Work with the Consortium to define important scientific questions that will determine biological sampling, outcome and exposure measures, and analytical plans.
  • Propose approaches to understand the cause or causes of CKDu. The approaches must provide grounded biological plausibility for proposed hypotheses. These may include targeted, untargeted and discovery analysis of blood, urine and kidney biopsy tissue of study participants using a wide range of approaches (including, but not limited to, metabolomics and proteomics) and studies examining genomic susceptibility. Studies designed to look at a single hypothesis are discouraged.
  • Devise biological sampling strategies to address hypotheses, recognizing the available resources within CKDu-endemic areas. The RSC will work with the FES, HHEAR and SDCC to develop protocols to maximize the scientific value of biological specimens (urine, blood, kidney tissue) obtained by the FES to test hypotheses and apply discovery methods to elucidate the cause or causes of CKDu. (HHEAR will perform environmental exposure analyses of biological and environmental samples.) The RSC will provide biological sample collection kits for the FESs and will include the expense of kits, renal function measurements, and state-of-the-art laboratory assays in their budget. The cost of shipping kits and specimens will be within the budget of the SDCC.
  • Measure renal function and markers of renal injury and repair in blood and urine.
  • Assist the FES in determining flexible strategies for preparation and handling of limited kidney biopsy samples, including strategies to preserve specimens for transcriptomic analysis.
  • Propose strategies for phenotyping of CKDu-affected participants that can be implemented at the FES and that are appropriate to the infrastructure of CKDu-endemic regions (resource-limited settings). These strategies may include, but are not limited to, studies of urinary concentration and dilution, ultrasound, or other measures testing renal function.
  • Use state-of-the-art methods for the analysis of biological samples. Capacity for proposed analyses must be available either through their own laboratory or through collaborators or contractors.
  • Assure quality control and quality assurance of samples and assays and will promptly share data with the wider research community once assurance is complete.

In furthering the work of the Consortium:

  • The RSC will work collaboratively with HHEAR to develop biological sampling strategies without overlap of capacity and to share samples for environmental exposures which may include blood, urine, hair, nails or other specimens.
  • The RSC must agree that the final design of the study, including selection of cases and controls, selection of outcomes, clinical variables and environmental exposure to measure and all other factors pertaining to the design and implementation of the study will be determined by the CURE Consortium Steering Committee. This will be based on input and deliberations by all members of the Consortium.
  • The RSC will accept the overall governance, common protocols, publication policies, collaborative procedures, confidentiality policies and data sharing plans to be developed by the CURE Consortium.
  • The Consortium will have its first steering committee as a face-to-face meeting on the NIH campus in the first year of award on September 20-21, 2021 and awardees must commit to attending this and all face-to-face meetings for the duration of the study. The Consortium will meet semi-annually in the Bethesda, MD area and awardees must attend and budget for travel to steering committee meetings.

This FOA will not support intervention trials to prevent or treat CKDu.

This FOA is intended to support only human studies and applications that include animal or model systems are not responsive.

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

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIDDK and NIEHS intend to commit $4,000,000 in Fiscal Year 2021 to support the three related funding opportunities RFA-DK-20-017, RFA-DK-20-018, and RFA-DK-20-019. We anticipate awarding 1 Scientific Data Coordinating Center, 1 Renal Science Core and 3-4 Field Epidemiology Sites.

Award Budget

Application budgets need to reflect the actual needs of the proposed project. Application budgets are anticipated to be no more than $400,000 direct costs per year for Years 1 and 2 and no more than $500,000 in Years 3-5. Award budgets will vary from year to year depending upon the scientific needs and opportunities of the consortium.

Award Project Period

The maximum project period is 5 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

  • 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 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.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

 

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.  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 NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

John F. Connaughton, Ph.D.

Chief, Scientific Review Branch

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

Telephone: 301-594-7797

Email: 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.

SF424(R&R) Senior/Key Person Profile

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

 

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

Applicants must budget for PI/PD(s) and co-PI(s) to travel to semi-annual face-to-face steering committee meetings in the Bethesda, MD area.

The RAC will provide biological sample collection kits for the Field Sites and should include these expenses in their budget.

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:

  • Scientific guidance: Discuss how the Renal Science Core (RSC) will provide scientific guidance for kidney research to the Consortium to determine the biological sampling strategies for participants with CKDu and controls enrolled in cross-sectional and longitudinal cohorts.
    • Describe a strategy and approach to address the cause or causes of CKDu and modifying factors. Describe a suggested selection of cases and various controls to be recruited by the Field Epidemiology Sites (FES). Describe baseline and longitudinal measures you would suggest the FES obtain.
  • Scientific strategies for collected biospecimens: Discuss how the RSC will maximize the scientific value of biospecimens (urine, blood, kidney tissue) to test hypotheses or apply discovery-based approaches elucidating the causes of CKDu. Describe the full range of state-of-the-art methods proposed for biological sample analyses.
  • Clinical phenotyping: Describe strategies for phenotyping of participants with CKDu and how they will be implemented in resource-limited settings.
  • Renal analyses: Describe the capacity of the RSC to perform measurements of renal function using blood and urine. Describe sampling strategies appropriate to the FES in CKDu-endemic regions to understand the course of the disease including progression, stabilization and episodes of acute kidney injury.
  • RSC Team: Clearly describe the formal organizational structure of the multidisciplinary team and how they will contribute to addressing the scientific questions posed. Describe the relevant experience to deliver reliable results, including preliminary data. (Do not duplicate capabilities available at HHEAR laboratories (https://hhearprogram.org/sample-matrix-table) for environmental exposure analyses of biological and environmental samples). If omics-based technologies are proposed, describe the available expertise to perform data analysis and interpret findings. Document the collaborative research experience of the team.
  • Biopsies: Describe the capability of the RSC to perform histology and pathologic interpretation of renal biopsies obtained by the FES.
    • Describe alternate plans to address the scientific questions if kidney tissue is limited.
  • Rigor and reproducibility: Describe how the RSC will ensure rigor and reproducibility in biological sample analysis including quality assurance and quality control of assays and sample collection.
  • Consortium collaboration: Document willingness to participate in the development and execution of common protocols for sample collection and renal science with the other members of the Consortium.

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.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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 Component of the SF424(R&R) Application Package. 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 DUNS number it provides on the application is the same number 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 components of participating organizations, 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" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

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

Specific to this FOA: Will the research design and approach advance our understanding of the cause or causes of CKDu, the exacerbating and protective factors, or the potential for therapeutic targets or public health interventions? Will the scientific guidance on biological sampling strategies and clinical phenotyping provided by the Renal Science Core (RSC) enhance the chances of success of the Consortium?

 

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: Is the organizational structure of the multidisciplinary team appropriate to the studies they have proposed? How effectively has the expertise in kidney research, pathophysiology and renal pathology been incorporated into the RSC? Does the expertise assembled in the RSC enhance the likelihood that the Consortium will make meaningful progress in understanding CKDu? Have the investigators clearly demonstrated they have the capability to perform histology and pathologic interpretation of renal biopsies?

 

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?

Specific to this FOA: Are the proposed innovations in scientific approach or analytic strategy likely to elucidate the cause or causes of CKDu? Will their approach shift the current paradigm of understanding of the causes of CKDu?

 

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?

Specific to this FOA: How well will the proposed strategy for biological sampling and analysis advance our understanding of the cause or causes of CKDu and the course of the disease? Have the investigators demonstrated that they can deliver reliable results from the measures they propose to collect at the Field Epidemiology Sites which are located in resource-limited settings? Will the proposed phenotyping strategies enhance our understanding of CKDu? Have the investigators adequately adapted their biological sampling and phenotyping strategies to resource-limited settings? Will the proposed state-of-the-art methods applied in the analysis of biological samples increase our understanding of CKDu? If omics-based technologies are proposed, how clearly have the investigators demonstrated they have the expertise to perform data analysis and interpret findings? How clearly have the investigators demonstrated they can ensure rigor and reproducibility in their sample analysis, including quality assurance and quality control of assays and sample collection? How clear and feasible are the plans to modify the analytic strategy if kidney tissue is not available and will this compromise the goals and aims of the study?

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?

 

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?

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.

 

Not applicable.

 

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). Have the applicants described their plans to make data promptly available to the wider research community?

 

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 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 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 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.
  • Evidence that the applicant and investigators are committed to policies as established by the Steering Committee including with regard to sharing of information and resources and cooperative interaction

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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: Grantee 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

 

After completion of the initial review, NIH program staff will be responsible for any additional administrative review of the plan for sharing data. The adequacy of any data sharing plan will be considered by program staff when making funding decisions. Any final accepted data sharing plan will become a term and condition of the award of the cooperative agreement

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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 “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, 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 awardees 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
 

The PD(s)/PI(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). Awardee(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Awardees 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 awardee/site is required to ensure that data will be submitted expeditiously to the Scientific 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 and completeness. Awardees 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 awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.

7. Reporting of the study findings.  Awardees 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 awardee 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 awardees consistent with NIH and study policies.

8. Any third-party (including industry, academia, and foundations) collaboration 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 industry, academia, and foundations) in the study and network activities that includes access to any network study 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 and steering committee policies on publications.

11.  Maintaining confidentiality of information:  The awardee(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. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. Prior to enrolling participants, the PI or his/her designee will coordinate with the NIDDK Central Repository to develop a Data Sharing Plan and prepare the collected data for eventual archiving and distribution. In addition, if applicable, the PI or his/her designee will work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, storage, and sharing of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study’s leadership will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Subsequently samples and data 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 data sharing in multi-center and large single-center clinical studies https://www.niddk.nih.gov/-/media/Files/Research-Funding/Process/PublicversionNIDDKdatasharingpolicy2013July2013.pdf.

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 awardee 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 awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee 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 awardees 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 awardees 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 awardees 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.
  1. 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.
  1. 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.
  1. 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.
  1. 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 Awardees 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 awardees, 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 of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK, in consultation with the Steering Committee. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Oversight Committee established by the NIDDK and by interacting closely with the awardees during protocol development and implementation.

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 awardee (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 awardee'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, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees 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 $25,000.  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 Appendix XII to 45 CFR Part 75, 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 – Award Term and Conditions 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)

Susan R. Mendley, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-1861
Email: susan.mendley@nih.gov

Bonnie R. Joubert, MPH, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3276
Email: bonnie.joubert@nih.gov

Peer Review Contact(s)

Ann A. Jerkins, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2242
Email: Ann.Jerkins@nih.gov

Financial/Grants Management Contact(s)

Helen Hunter Cox, MHS
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-496-7274
Email: Helen.Cox@nih.gov
 

Jenny Greer
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3332
Email: jenny.greer@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.


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