Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium- Renal and Environmental Science Core (U01-Clinical Trial Not Allowed)

Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium- Renal and Environmental Science Core (U01-Clinical Trial Not Allowed) is sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This funding opportunity supports the continuation of the Consortium to Study Chronic Kidney Disease of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE).

Expired RFA-DK-20-018: Chronic Kidney Diseases of UnceRtain Etiology (CKDu) in Agricultural Communities (CURE) Research Consortium Renal Science Core (U01 - Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. 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) U01 Research Project Cooperative Agreements 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 Companion Funding Opportunity RFA-DK-20-017 , U01 Research Project - Cooperative Agreements, RFA-DK-20-019 , U24 Resource-Related Research Projects - Cooperative Agreements See Section III.

3. Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) 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.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 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) 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.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

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.

Funding Opportunity Description 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.

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.

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. 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).

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. 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 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 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. 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 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.

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 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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.

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. 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.

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. 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) 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.

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. 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.

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

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 (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. 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