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

This Funding Opportunity Announcement (FOA) requests applications for the Kidney Precision Medicine Project (KPMP) Recruitment Sites (RS) to recruit adult men and women with either acute kidney injury (AKI) or chronic kidney disease (CKD) for longitudinal cohort studies that include a research kidney biopsy. The RS should work collaboratively to capture demographic information, conduct longitudinal clinical phenotyping, and collect biological samples in a standardized manner. It is anticipated that the KPMP will change clinical culture and paradigms so that clinical and research kidney biopsies are performed more commonly in people with AKI and CKD.

Applicant teams should have documented experience with patient recruitment and safely obtaining kidney biopsies for clinical and/or research purposes. The primary objective of the UG3 exploratory phase will be to demonstrate that the site can recruit participants with either AKI or CKD and obtain high-quality research kidney biopsies, while ensuring safety, minimizing risk and conforming to the highest ethical, research and clinical standards. UG3 awards that have met their milestones will be administratively considered by the NIDDK and prioritized for transition to the UH3 implementation phase. UH3 awards will support continued recruitment into successively larger cohort studies. Projects proposed in response to this FOA will require a multidisciplinary team including nephrologists, critical care physicians, primary care physicians, radiologists, pathologists, statisticians, ethicists, patients, and patient advocates. Investigators responding to this FOA must address both the UG3 and UH3 phases. This FOA is intended to support only human studies and applications that include animal or model systems are not responsive.

The RS will work collaboratively with the KPMP Tissue Interrogation Sites (TIS; RFA-DK-16-027) and Central Hub (CH; RFA-DK-16-028) to obtain, process, evaluate and visualize data. All data and samples will be submitted to the CH for analysis by the KPMP investigators, and as appropriate, the broader scientific community.

AKI and CKD impose a significant global health burden. Yet, no effective therapies currently exist for AKI, and only a few are available for CKD. Community feedback indicates that despite significant effort from industry and academia development of pharmacologic therapies for AKI and CKD has been hampered by non-predictive animal models, the inability to identify and prioritize human targets, the limited availability of human kidney biopsy tissue, and a poor understanding of AKI and CKD heterogeneity [Kidney Research National Dialogue 2014; AKI Outcomes Meeting 2015; Kidney Precision Medicine Meeting 2016]. Historically, AKI and CKD have been described as single, uniform diseases; however, growing consensus suggests that different disease pathways lead to different subgroups of AKI and CKD (AKIs and CKDs). Access to human kidney biopsy tissue is a critical first step to define disease heterogeneity and determine the precise molecular pathways that will facilitate identification of specific drug targets and ultimately enable individualized care for people with AKI and CKD.

Recent advances in multi-scale interrogation of human tissue and single cells have set the stage for precision medicine to be applied to AKI and CKD. The objectives of the KPMP are to ethically obtain and evaluate human kidney biopsies from participants with AKI or CKD, create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways and targets for novel therapies. The KPMP will be made up of three distinct, but highly interactive activities:

1. Recruitment Sites: recruit people with AKI or CKD for longitudinal cohort studies that include a research kidney biopsy (this FOA).

2. Tissue Interrogation Sites: use and develop innovative technologies to analyze human kidney tissue.

3. Central Hub: aggregate, analyze and visualize all data and samples, and provide scientific, infrastructure and administrative support for the entire KPMP.

All data and samples from the RS and TIS will go to the CH. In addition to an Administrative Core (AC), the CH will have a Data and samples Coordinating Center (DCC) and a Data Visualization Center (DVC). The DCC will perform standard clinical data assessments (e.g., patient data reports, recruitment tables, observational study reports), whereas the DVC will perform digital pathological assessments and create a kidney tissue atlas (incorporating data and images generated by the RS and TIS) to help define disease subgroups and identify critical cells, pathways and targets for novel therapies. The DVC will also manage a KPMP website to facilitate the sharing of all de-identified data and samples with the broader research community.

While kidney tissue from transplant, nephrectomy, and autopsy will be used to optimize tissue interrogation methods, these do not provide the quality and diversity of tissue to meet all of the KPMP objectives. The KPMP requires research kidney biopsies (or clinical biopsies with research core(s); collectively called research kidney biopsies throughout this document) linked to longitudinal clinical phenotypic data and biosamples.

It is anticipated that the KPMP will be conducted in stages:

• Stage 1: Optimize and validate tissue processing and interrogation methods. Establish common clinical protocols and cohort studies enrolling a small number of AKI or CKD patients. Assess quality of phenotype data and biopsy protocols at each site. Begin work on kidney tissue atlas. Optimize next generation assays.
• Stage 2: Small scale proof of concept studies to determine if clinical and analytic pipelines are robust. Enrich the kidney tissue atlas. Implement next generation tissue interrogation assays. Expand longitudinal cohort studies in initial AKI or CKD populations.
• Stage 3: Expand to larger cohort studies (expected next project period).

To provide a community resource for advancing research in this area, all KPMP activities must meet rigorous sharing and quality control standards. Given the risk of complications from kidney biopsy, the KPMP will hold ethical and participant safety considerations paramount. The KPMP will work closely with participants to ensure that their viewpoints, priorities, and preferences inform all aspects. All of the KPMP activities will be overseen by an Observational Safety Monitoring Board (OSMB) constituted by the NIDDK that will focus on participant safety, study burden and scientific validity of the clinical data; and an External Evaluation Panel (EEP) constituted by the NIDDK that will focus on the overall scientific progress and direction of the KPMP.

Applicants must propose to recruit patients with either AKI or CKD for a longitudinal cohort study, including a research kidney biopsy. Essential objectives include:

1. Recruitment

• Propose to study either AKI or CKD, specify the initial disease cohort(s) of interest, provide inclusion/exclusion criteria, and estimate the number of participants to be recruited given the budget specified in this FOA and required KPMP objectives.
• Adhere to the highest ethical principles of clinical research, including fully informed consent for a research kidney biopsy.
• Include collaborators with expertise in research ethics who are knowledgeable about the use of biopsy tissue in research. Also include collaborators knowledgeable and skilled in biopsy of the kidney; such individuals should have an exceptional safety record and provide statistics regarding complications from kidney biopsies they have performed.
• Enlist local involvement of participants, practitioners and ethicists, as well as Institutional Review Boards (IRBs), and the CH Patient Engagement Working Group, to develop safe and acceptable procedures for the performance of kidney research biopsies in patients with either AKI or CKD.
• Possess the ability to consent for genetic studies and (re)consent for additional longitudinal data and biosample collection, and future intervention studies.

2. Collection of kidney biopsy, biosamples and data

• Safely perform research kidney biopsies using the KPMP approved protocols for training, biopsy performance, and tissue handling, processing and shipping.
• Collect longitudinal clinical phenotypic data (e.g., medications, comorbidities, birthweight, socioeconomic status, imaging studies) and biosamples (e.g., blood, urine, stool). Where possible, link all data and samples to participant Electronic Health Records (EHRs).
• Supply other sources of existing healthy and diseased kidney tissue (e.g., obtained from transplant, nephrectomy, autopsy) for optimization, discovery and validation efforts. Harmonize existing samples and data with new efforts.

3. Collaboration and sharing

• Work collaboratively as a member of the KPMP Steering Committee (SC) to identify important scientific questions.
• Develop common study protocols for data collection, written informed consent, performance of research kidney biopsies (including specialized training for the performance of research biopsies), and for tissue handling, processing and shipping.
• Participate in a program of data and sample quality improvement, established by the KPMP, and modify procedures as necessary.
• Submit all data and samples to the CH, including routine clinical pathologic slides and clinical pathology reports. The CH will in turn perform conventional and advanced (e.g., omic, 3-Dimensional imaging) pathologic reading of all available tissue, compare to the clinical diagnosis and local site pathologic analysis, and examine if it is feasible to provide clinical feedback to the practitioner caring for participants enrolled in the KPMP.
• Data and samples will be used to support future ancillary studies to the KPMP (funded through the CH Opportunity Pool and other mechanisms).

The KPMP investigators will collaboratively devise a set of studies that will be reviewed by the EEP and approved by the NIDDK. Thus, all studies proposed in the applications will be a starting point for discussions regarding the research to be undertaken. It is unlikely that any proposed research will be undertaken exactly as planned, or at an individual site. This FOA is intended to support only human studies and applications that include animal or model systems are not responsive.

Initial cooperative agreement awards will be granted for an exploratory (UG3) phase to demonstrate that the site can recruit participants with either AKI or CKD, and obtain high-quality research kidney biopsies, while minimizing risk, ensuring safety and conforming to the highest ethical, research and clinical standards. The samples will be used initially by the TIS to test, optimize and validate tissue interrogation methods. The most promising UG3 projects may be approved for transition to the implementation (UH3) phase of the award. The UH3 phase will allow continued recruitment into successively larger longitudinal cohort studies.

Objectives for UG3 Exploratory Phase:

Investigators should have documented experience with AKI or CKD recruitment and safely obtaining kidney biopsies for clinical and/or research purposes.

The UG3 phase will:

• Develop and implement common clinical protocols and collaborative cohort studies in initial AKI or CKD populations.
• Demonstrate that sites can safely obtain research kidney biopsies using the KPMP approved protocols for training, biopsy performance, and tissue handling, processing and shipping.
• Recruit participants with either AKI or CKD for longitudinal research kidney biopsy cohort studies. The biopsies will be used initially by the TIS to test, optimize and validate tissue interrogation methods.
• Collect longitudinal clinical phenotypic data (e.g., medications, comorbidities, birthweight, socioeconomic status, clinical imaging studies) and biosamples (e.g., blood, urine, stool). Where possible, link all data and samples to participant Electronic Health Records (EHRs).
• Submit all samples and data to the CH.
• Test quality of phenotypic data, biopsy protocols, and biopsy material at each site and modify if necessary to improve performance.

Transition from UG3 phase to UH3 phase:

The UG3 phase must include milestones that will be evaluated during peer review and used as the basis of programmatic review at the transition time. Final milestones will be established during the first year of the UG3 phase. Performance milestones will be evaluated before the UG3 award is transitioned to the UH3 phase after the second year of funding.

It is suggested that applicants consider the demonstration of the following when developing milestones for the application:

• Recruitment of participants with either AKI or CKD
• Participant consent for follow-up, recontact and reconsent
• Collection of longitudinal clinical phenotypic data, kidney biopsies, biosamples and data
• Measures of patient safety related to kidney biopsy
• Measures of quality control regarding kidney biopsies, biosamples and data
• Measures of acceptability for the kidney biopsy by participants (metrics to be developed in collaboration with the CH Patient Engagement Working Group).
• Sharing and harmonization of other sources of kidney tissue, biosamples and data
• Collaboration and sharing of all protocols, tissue, samples and data

After administrative review by the NIDDK (in consultation with the EEP and OSMB), successful UG3 projects will be prioritized and may be approved for transition to UH3 funding.

Criteria used to determine which UG3 projects will be continued into the UH3 phase include the following:

• Successful achievement of milestones for the UG3 phase
• Adhering to the highest ethical principles of clinical research, including fully informed consent for a research kidney biopsy
• Meeting participant recruitment goals
• Obtaining high-rates of participant consent for follow-up, recontact and reconsent
• Obtaining high-quality kidney research biopsies
• Ensuring participant safety and minimizing complications of kidney biopsy
• Successful collection of longitudinal clinical phenotypic data and biosamples
• Potential of plan to successfully expand cohort studies in initial AKI or CKD populations
• Successful sharing and harmonization of other sources of samples and data as appropriate and consistent with achieving the goals of the KPMP Achieving acceptable tissue, sample and data quality control metrics
• Working collaboratively with the KPMP investigators and sharing all protocols, samples and data as appropriate and consistent with achieving the goals of the KPMP
• Contributions to the scientific output of the KPMP
• Potential for meeting the overall objectives of the KPMP

Transition will also depend on the NIDDK program priorities, leadership approval and availability of funds.

Objectives for UH3 Implementation Phase:

The UH3 phase must include plans for continued recruitment and expanding initial cohort studies.

Expected outcomes for UH3 phase include:

• Small scale proof of concept study to test if clinical and analytic pipelines are robust
• Expand cohort studies in initial AKI or CKD populations
• Continued implementation and sharing of all protocols, tissue, samples and data

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

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

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)

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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

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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

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.

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).

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow the instructions in the Research Instructions for the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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, preferably electronically, should be sent to:

Michele Barnard, Ph.D.
Deputy Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Rm. 7353
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: 301-594-8898
Fax: 301-480-3505
Email: [email protected]

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

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

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

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

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

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

Include collaborators with expertise in research ethics who are knowledgeable about the use of biopsy tissue in research. Also include collaborators knowledgeable and skilled in biopsy of the kidney; such individuals should have an exceptional safety record and the statistics of complications from kidney biopsy should be provided.

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

Applications should budget for the following:

• Costs for kidney biopsies for research purposes. Specify the number of clinical biopsies with research cores, and the number of non-clinically indicated research biopsies. Justify the number of research kidney biopsies required to achieve the proposed objectives of this FOA.
• PD(s)/PI(s) are required to declare a minimum effort of 2.4 person-months (20 percent) effort per year. Applications proposing Multiple PD(s)/PIs(s) must have a minimum combined PD/PI effort of 2.4 person months.
• Research coordinator(s) for IRB submission of protocol/consent forms, training, and implementation of the protocol for longitudinal follow up of the cohort participants.
• Arrangement of logistical services for protocol-specific costs, including subcontracts and supplies. Do not budget for shipping of samples and data. These costs will be covered by the CH.
• Support for the activities as member(s) of the SC, including in-person travel to Bethesda MD/Washington DC area at least two times per year throughout the project period, including the launch meeting anticipated in August or September of 2017. This should include the travel of patient representatives to face-to-face meetings of the SC and Patient Engagement Working Group.

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

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:

Specific Aims: Provide the overall objectives for the entire application, and indicate separately, Specific Aims to be accomplished in the UG3 phase and in the UH3 phase. This FOA is intended to support only human studies and applications that include animal or model systems are not responsive.

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

1) Background and Significance

• Applicants for a RS should identify as either an AKI or CKD site.
• Discuss the scientific questions that need to be addressed from longitudinal cohort(s) studies, in particular, the objectives to create a kidney tissue atlas, define disease subgroups, and identify critical cells, disease/repair pathways and molecular targets.
• Discuss the potential to improve treatment for individuals with AKI or CKD.
• Discuss ethical and safety issues in obtaining a research kidney biopsy in participants with either AKI or CKD.
• Discuss the challenges in obtaining kidney biopsies in participants with AKI or CKD, especially from historically disenfranchised communities.
• Discuss the number of biopsies necessary to achieve the KPMP objectives.

2) Preliminary Data

• Demonstrate that the site will ensure safety, minimize risk and conform to the highest ethical, research and clinical standards. In particular, applicants should describe how both patient and physician attitudes, opinions and beliefs about the acceptability of kidney biopsies for research will be considered. This will likely involve diverse and multidisciplinary teams including critical care physicians, primary care physicians, nephrologists, radiologists, ethicists, members of IRBs and patients. Applicants should outline how such discussions will take place at the start of studies and as research progresses.
• Establish a local participant panel that will review recruitment strategies and biopsy protocols, and provide advice to site researchers on approaches to educate participants about the need for research kidney biopsies and obtain informed consent for the KPMP studies. Do not propose to use national groups such as the Patient and Family Partnership of the Kidney Health Initiative (KHI; a joint venture between the American Society of Nephrology and FDA), as they will be added once the KPMP is formed.
• Demonstrate knowledge and understanding of the ethical issues involved in collecting kidney biopsy tissue for research purposes. This is especially important for AKI or CKD participants who have not been traditionally biopsied or are from groups that are generally underrepresented in research studies or historically disenfranchised communities. Applicants should present culturally sensitive, and medically and ethically appropriate plans, for engaging participants from such populations in research, and obtaining informed consent in a meaningful manner.
• Demonstrate pre-application involvement of the local IRB, and tentative agreement by the IRB, for a study in which kidney biopsy tissue is collected for research, as well as for clinical pathology. The NIH realizes that the common protocol(s) will need to be approved by all IRBs at a later date.
• Document the number of clinical and research kidney biopsies performed previously and provide statistics regarding complications.
• Discuss other sources of existing healthy or diseased data and samples (including archived tissue) to be used for optimization, discovery and validation efforts. (Note: any existing data or samples discussed in the application must be made available to the KPMP upon award.) Document willingness to share all data and samples, as appropriate, and discuss how they will be harmonized with new efforts.

3) Activities and Management of the Multidisciplinary Team

• Clearly describe the formal organizational structure of the multidisciplinary team, including lines of authority and responsibility, with particular attention to the relationship of the organizational structure to the major objectives of the KPMP.
• Document the clinical research experience of the team in recruitment, retention and other key areas.
• Document willingness to accept the overall governance, common protocols, publication policies, collaborative procedures, confidentiality and data sharing plans (including the sharing of pathologic slides and reports) to be developed by the KPMP.
• Confirm willingness to attend the KPMP launch meeting in the Bethesda MD/Washington DC area in August or September of 2017 to begin developing common protocols. Applicants should also state their willingness to work collaboratively with the other KPMP investigators on conference calls, working groups, SC meetings, and in the dissemination of research findings through publication or presentation.
• Confirm willingness to share all protocols, data and biosamples, including routine clinical pathologic slides and reports. The CH will perform conventional and advanced (e.g., omic, 3-Dimensional imaging) pathologic reading of all available tissue and compare to the clinical diagnosis and local site pathologic analysis.
• Describe training, procedures and experience necessary to safely obtain usable tissue from a kidney biopsy from patients with either AKI or CKD. For example, will all biopsies be performed by a single team? Describe methods to minimize variability across sites.
• Propose innovative ways of training individuals in recruitment, biopsy performance and data collection.
• Document that AKI or CKD participant recruitment can begin by April 2018.
• Industry (Pharmaceutical and Biotechnology) may participate in the KPMP to expand the scope, size, and/or complexity of the project. State a willingness to work with Industry partners/collaborators in a pre-competitive research arena.

4) Approach divided in two parts corresponding to the UG3 and UH3 phases:

Applicants should propose and justify a phased approach to study either AKI or CKD over the project period specified in this FOA. This should include: a UG3 exploratory phase to demonstrate that the site can recruit participants with either AKI or CKD, and safely obtain high-quality research kidney biopsies, while conforming to the highest ethical, research and clinical standards; and a UH3 implementation phase to support continued recruitment and expansion of initial longitudinal cohort studies. Applicants should propose specific inclusion/exclusion criteria [including key clinical cohorts (e.g., diabetic CKD), duration of disease, level of kidney function, age, comorbidities, gender, race/ethnicity, medications, environmental exposures, and other factors deemed important for the study or potential ancillary studies]. Each phase must be justified, including the number of biopsies needed to achieve the phased objectives, and specific milestones must be proposed.

UG3 exploratory phase - address each of the items listed below.

• Applicants should propose to study either AKI or CKD.
• AKI is not a single disease. Applicants should justify whether to study all AKI, or may propose to initially study specific cohort(s) (specify inclusion/exclusion criteria), and then proceed to a more inclusive cohort design. Applicants for AKI sites should determine how pre-renal azotemia will be identified, establish initial parameters for the delineation of acute tubular necrosis (ATN), and discuss the inclusion/exclusion criteria for the initial cohort. AKI sites should propose a plan for presenting risks and benefits to participants, acquiring written informed consent, and ensuring safety and minimizing research risks in critical care settings, where participants may have clinical conditions such as hypotension, coagulopathy and ongoing tertiary care.
• CKD is not a single disease. Applicants should justify whether to study participants with CKD at early or later stages, or may propose to initially study a specific cohort(s) (specify inclusion/exclusion criteria), and then proceed to a more inclusive cohort design. CKD sites should propose a plan for presenting risks and benefits to participants, acquiring written informed consent, and ensuring safety and minimizing research risks.
• Describe the number of AKI or CKD participants expected to be recruited that meet the inclusion/exclusion criteria proposed. Details of collaborations with other longitudinal cohort studies or other subcontracted sites should be provided. Backup recruitment plans are encouraged. Efficient use of EHRs for recruitment is encouraged.
• Discuss plans to ensure appropriate diversity (sex, race and ethnicity).
• Describe the number of non-clinically indicated research kidney biopsies and the number of clinical biopsies with research cores that will be obtained each year.
• Complete follow-up of participants will be necessary to avoid bias. Discuss how participants will be followed. Propose protocols for collection of longitudinal data, including follow-up visits and biosample collection. Discuss the type and frequency of collection of phenotypic data (including patient reported outcomes [PRO], clinical and laboratory data), genomic data, biochemical data, medications, research kidney biopsy and other biosamples. All proposed measurements should be justified by the proposed scientific question(s). Efficient use of EHRs for follow-up is encouraged.
• Discuss details of transmission of phenotypic data and transport of biosamples to the CH.
• Discuss other sources of existing healthy or diseased sample/data collections (including archived tissue) to be used for optimization, discovery and validation efforts. (Note: any sample/data collection discussed in the application must be made available to the KPMP if the application is funded.) State a willingness to share all samples and data, as appropriate, and discuss how they will be harmonized with new efforts.
• Propose consent for genetic studies and potential (re)consent for additional longitudinal data and biosample collection, and future intervention studies. Discuss the ethics and feasibility of repeat biopsies.
• Propose specific milestones that will be used to evaluate success of the RS throughout the duration the UG3 exploratory phase and particularly for evaluating the transition from the UG3 to UH3.

UH3 implementation phase - address each of the items listed below.

• Describe the research objectives to be addressed during the UH3 phase.
• Design expanded cohort studies in initial AKI or CKD populations.
• Describe the scale-up of patient recruitment, consent, research biopsy, and sample/data collection with careful attention to participant safety, retention and quality metrics.
• Describe the number of biopsies needed to achieve the objectives of this phase.
• Propose specific milestones that will be used to evaluate progress of the UH3 implementation phase.

Milestones and timelines

A timeline including milestones is required for each phase (UG3/UH3). Milestones are objectives that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Milestones should function as indicators of continued progress, thus revealing emergent difficulties, and will be used to evaluate the application not only in peer review, but also when considering the awarded project for funding of non-competing award years. Milestones must be defined in the application. Timelines must state when metrics for assessment of progress in both the UG3 and UH3 phases will be achieved, including specific milestones for progressing from the UG3 phase to the UH3 phase. At the end of the "Approach" section for the UG3 and UH3 subsections, milestones and timelines should be provided under separate headings. The following are particularly important:

• Provide appropriately detailed (quantitative) criteria by which milestone achievement will be assessed;
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall objective; and
• Identify any impediments that could require modification to the research plan, milestones, and/or timeline with a discussion of alternative approaches.

Letters of Support: A letter from the local IRB should be included in the application indicating their willingness to review future common protocol(s) for obtaining research kidney biopsies.

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, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All applications under KPMP will be required to submit a data sharing plan. Applicants and their institutions are expected to describe their plans for making all protocols, technologies, data, samples and other research resources broadly available to the research community. Applicants should include in their data sharing plan the assurance that data and samples will be made available as soon as quality control procedures have been completed at the local institution. Any sharing plans by the institution represent a commitment by the institution (and its subcontractors, if any) to support and abide by the plan.
• This plan should also address methods for continuing to make the KPMP data available to the NIH and the research community upon completion or termination of the site so that accumulated data remain accessible, for example, through the NIDDK Central Repositories.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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.

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

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.

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.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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

Are the proposed scientific questions and proposed studies sufficiently compelling to justify research kidney biopsies? Will the biopsies be performed in a way that maximizes their value as a precious resource?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Do the applicants have sufficient expertise and experience in safely obtaining kidney biopsy tissue for research purposes? Have the applicants provided statistics regarding complications from kidney biopsies they have performed? Is the expertise of the proposed multidisciplinary team adequate? Have the applicants demonstrated a willingness to accept the overall governance, common protocols, publication policies, collaborative procedures, confidentiality and data sharing plans (including the sharing of pathologic slides and reports) to be developed by the KPMP?

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?

Have the applicants proposed novel methods to safely perform kidney biopsies and obtain research kidney tissue? Have the applicants proposed novel methods to ensure optimal processing, storage and transfer of biopsy tissue and biosamples?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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?

Are there sufficient plans to minimize risk, enhance safety and conform to the highest ethical, research and clinical standards? Have the applicants provided a strong rationale for the number of biopsy samples/study participants needed for AKI or CKD studies at each phase? Are the plans for selection and recruitment of initial patients and disease cohort(s) (with specific inclusion and exclusion criteria) appropriate? Has the IRB supplied evidence that procurement of kidney tissue will be acceptable? Does the proposed consent include genetic studies, additional longitudinal data and biosample collection, and future intervention studies? Is the initial data collection linked to longitudinal clinical and EHR data? Have the applicants identified other sources of existing healthy or diseased sample/data (including archived tissue)? Did the applicants state a willingness to share all samples and data, as appropriate, and discuss how they will be harmonized with new efforts?

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 children, 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?

Does the environment support sufficient patient recruitment potential? Is there evidence of support from the necessary institutional groups, including medicine, primary care, radiology and critical care departments (where needed)? Is there evidence that the participant EHRs can be linked to samples and shared outside of the parent institution? Is the institutional EHR system adequate to support the proposed objectives?

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.

UG3/UH3 Milestones and Timeline

Is the overall plan for the transition from the UG3 exploratory phase to the UH3 implementation phase well thought out? Is the UG3 phase clearly defined, logical and complete? Are milestones provided for the UG3 phase quantitative whenever appropriate? Are these milestones well-aligned with the specific aims of the Research Objectives? How realistic are these milestones and associated timelines? Do the proposed milestones and timelines clearly identify benchmarks for successful completion of the UG3 phase? Are other critical go/no go decision points and timelines well defined and appropriate?

For research that involves human subjects but does not involve one of the six 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 six 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 children 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

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• 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.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Evidence that the applicant and investigators are committed to policies as established by the SC including with regard to confidentiality, sharing of information and resources, and cooperative interaction.
• Evidence of previous productive, cooperative, collaborative interaction.
• Diverse recruitment and complementary approaches are being applied across the KPMP.

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.

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.

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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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.

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.

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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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. The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report and the UG3/UH3 transition.

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 primary responsibility of the PD(s)/PI(s) will be:

• Determine experimental approaches, design protocols, ensure participant safety, set project milestones, conduct experiments, and analyze and interpret research data.
• Provide objectives for projects and protocols and costs to the NIH Project Officer (PO) and Project Scientist (PS), at the outset of the award, following re-negotiation of the milestones after the first meeting of the SC and at six months intervals thereafter, in consultation with the KPMP, PO, PS, EEP and OSMB.
• Ensure that all projects involving human subjects have the appropriate clearances (e.g., IRB, Federalwide Assurance, human subject s research training, and other required documentation) prior to implementation.
• Serve as a voting member of the SC, and participate, along with critical staff, in SC meetings including two face-to face meetings per year in the Bethesda MD/Washington DC area.
• Adhere to the KPMP guidelines and other policies that might be established, as agreed upon by the SC, and the PO to the extent consistent with the applicant’s submitted statements and applicable grant regulations.
• Apprise the PO and PS of any potential impediments to execution of the objectives of the project.
• Ensure that primary and secondary data, protocols, procedures and any other project-derived resources are made available to the KPMP (e.g., deposited in a centralized database, as specified by the PO and PS) according to a timeline agreed upon by the SC and PO and to the extent consistent with the applicant’s submitted statements and applicable grant regulations.
• Providing representation on all relevant subcommittees and working groups established by the SC. Issues to address in working groups may include participant safety, quality control, pathology, molecular interrogation, ancillary studies, publication, intellectual property, data access, etc.
• Agree not to disclose confidential information obtained from other members of the KPMP and agree to the KPMP intellectual property agreements, consistent with the terms and conditions of the cooperative agreement awards, applicable regulations, and the policies and practices of the awardee institutions.
• Be prepared for annual administrative site visits by NIH staff.
• Be solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the awardee to perform the project.
• Be required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sec. 200-212 (Bayh-Dole Act).
• Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
• 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.

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

NIH Project Scientists (PS)

The role of the PS in the cooperative agreement is to support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibilities that remain with the PD(s)/PI(s). The PS will:

• Work closely with the PD(s)/PI(s) and other KPMP investigators to facilitate collaborations and to leverage the resources available to the sites and the KPMP. They will assist in the integration of the individual RS, TIS, and CH sites into a collaborative research project.
• Monitor the progress of the Recruitment Sites, Interrogation Sites, and CH, help coordinate research approaches, and contribute to the shaping of research projects or approaches as warranted. The PS will support and facilitate this process but will not direct it.
• Assist in avoiding unnecessary duplication of effort across the KPMP, and help coordinate collaborative research efforts that involve multiple sites.
• Keep the PDs/PIs informed about other ongoing studies supported by the NIH to avoid duplication of effort and encourage resource sharing and collaboration. The PS will coordinate access to other NIH resources, as well as assist the research efforts of the KPMP by facilitating access to fiscal and intellectual resources provided by industry, private foundations, NIH intramural scientists and other federal government agencies as appropriate.
• Serve as voting members of the SC and assist in developing the KPMP priorities and research agenda, operating guidelines and consistent policies for dealing with situations that require coordinated action.
• Retain the option to recommend to the PO the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its objectives according to the milestones agreed to at the time of the award or fails to comply with the Terms and Conditions of the award.
• Serve as scientific liaison between the awardees and other NIH program staff.
• Review and comment on critical stages of the KPMP progress.
• Share opportunities and discuss strategies and potential avenues of collaborations (such as with industry, private foundations and/or NIH intramural scientists).

NIH Program Official (PO)

The PO is responsible for the normal scientific and programmatic stewardship of the award. The PO will:

• Provide approval for transition of projects to the UH3 phase.
• Form an EEP and OSMB, comprised of the PS, PO, other NIH extramural staff with relevant scientific expertise or who manage research grant programs that relate scientifically to the objectives of the KPMP, and outside experts selected by the NIH.
• Have the option to recommend, following consultation with the EEP and OSMB (if applicable), the possible withholding, reduction, or reallocation, as appropriate, of support from any KPMP component that substantially fails to achieve its objectives according to the milestones agreed to at the time of the award or fails to comply with the Terms and Conditions of the award, at the appropriate times.
• Have the option to recommend, following consultation with the EEP and OSMB (if applicable), an increase in support to engage in further research efforts within the original research scope, as appropriate, for any KPMP component exceeding its objectives according to the approved milestones and substantially improving state-of-the-art capabilities, at the appropriate times.
• Participate in the SC meetings as an ex officio (non-voting) member.
• Retain the option to recommend, with the advice of the NIH PS, re-allocation of NIH support among awardees, as scientific objectives evolve.
• Carry-out continuous review of all activities to ensure objectives are being met.
• Serve as the official NIH representative in all communication with the SC.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The SC will be the primary governing body for all KPMP scientific activities. The SC will coordinate all sites awarded under these FOAs. The voting membership of the SC will include: one PD/PI from each award made under this and the companion FOAs, the NIH PS, and a representative from the Patient Engagement Working Group of the CH. The Chair of the SC will be assigned by NIH Program Staff, and may be chosen from outside the KPMP. Face-to-face meetings of this committee will occur at least two times a year. A portion of the SC meeting may be open to the public.

SC Composition - Voting members of the SC may include:

• The Program Directors/Principal Investigators (PDs/PIs) of each KPMP award
• The NIH Project Scientists (together representing a minority of voting members - not to exceed 1/3 of SC membership). Other NIH Program staff may attend the meeting as non-voting members.

SC Functions

The SC will be the primary governing body for all of the KPMP scientific activities. The SC will coordinate all projects awarded under the KPMP FOAs.

The role of the SC includes:

• Foster collaboration, synergy and sharing among the KPMP sites and investigators.
• Provide the primary mechanism for interactions with the NIH.
• Oversee the planning of the KPMP scientific activities, including dynamic adjustment as needs and opportunities arise.
• Guide the development and documentation of the KPMP standards and guidelines.
• Prioritize the use of the KPMP resources including systems biology analyses and bioinformatics.
• Evaluate progress in the KPMP sites and recommend adjustments in approaches if necessary, including implementation of new projects and changes to ongoing studies and termination of projects and sites.
• Foster partnerships and collaborations that will facilitate the extension of the approach to new technologies and their application to related kidney disease.
• Develop and approve the KPMP-wide intellectual property agreements consistent with the terms and conditions of the cooperative agreement awards, applicable regulations, and the policies and practices of the awardee institutions.

Responsibilities of the SC include:

• The SC will convene at least two face-to-face meetings a year in the Bethesda MD/Washington DC area. The first meeting will be a two-day meeting in August or September of 2017. Additional regular meetings will be conducted by teleconference or videoconference. Prior to each meeting, teleconference or videoconference, the SC Chair will prepare an agenda for review and approval, and distribute to members of the SC. Following these meetings, a list of participants and summary of discussion, action items, and recommendations will be prepared and submitted to the PO by the SC. Part of these meetings may be open to the public. The SC Chair may convene additional teleconferences, videoconferences, or electronic reviews to avoid delays in addressing key issues that cannot be evaluated at the regularly scheduled meetings. Regularly scheduled SC meetings will be convened in order to:
• Review progress of the KPMP sites; review progress of standardization and validation studies, other performance assessments, and future plans; and take remedial actions to address delays or other problems.
• Make recommendations to the KPMP sites about informatics and data and/or information management processes.
• Awardee members of KPMP will be required to accept and implement policies approved by the SC.
• The SC may make recommendations to the CH to establish working groups, or assign responsibility to key staff for other KPMP-related activities.

Data Sharing

• The data sharing plan will be referenced as a term and condition of award. Applicant organizations must comply with the Public Health Service (PHS) policies relating to distribution of unique research resources produced with PHS funding and sharing of all research protocols, data, samples and other research resources, as well as the grantee’s data sharing plan subject to decisions of the SC. For further information, see the NIH Data Sharing Policy at https://grants.nih.gov/grants/policy/data_sharing/.
• The NIH intends for the resource sharing plans for the data and samples generated under the KPMP to follow the policy and objectives stated in the FOA. Specifically, consistent with achieving the objectives of the KPMP, all protocols (clinical and research), data (including processed/analyzed data) and samples (including research kidney biopsies and other biosamples) generated are expected to be deposited in a SC-specified repository as soon as quality control procedures have been completed and on a timeline defined by the SC for use by the broad biomedical community, and for these data to remain available to all qualified investigators, consistent with applicable laws, regulations, and policies and unencumbered by any intellectual property claims. The NIH, in consultation with the SC for this project, will make all final decisions concerning data and sample deposition and data access policies, and all policies are subject to change by the NIH as deemed necessary to sustain program principles and priorities, or to ensure the highest standards for responsible research conduct within the project.
• Applicant organizations will comply with and implement the recommendations and decisions of the SC with respect to the sharing of information, data, biosamples, protocols, resources, and methods developed by the KPMP investigators under the KPMP.
• This plan should also address methods for continuing to make the KPMP data available to the NIH and the research community upon completion or termination of the site so that accumulated data remain accessible, for example, through the NIDDK Central Repositories.

Dispute Resolution

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

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 progress report, 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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

For Chronic Kidney Disease Recruitment Sites:

Michael Flessner, M.D., Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-4901
Email: [email protected]

For Acute Kidney Injury Recruitment Sites:

Paul L. Kimmel, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-1409
Email: [email protected]

Jason Hoffert, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-496-9010
Email: [email protected]

Carolyn Kofa-Sullivan
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7687
Email:[email protected]

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

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