It is critical that applicants follow the Multi-Project (M) Instructions in 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

Background

Understanding and ameliorating autosomal dominant PKD and autosomal recessive PKD are central to the mission of NIDDK. The clinical course of these diseases is highly variable; some patients develop only a modest number of renal cysts, while others develop a massive number of renal cysts and renal failure at an early age. The diseases have extra-renal manifestations, including in liver and systemic vasculature, with variable penetrance. The common underlying mechanisms are unknown despite important advances in elucidating causative genetic defects.

In 1999, the NIDDK originally established the PKD Research and Translation Core Centers, which functioned as stand-alone centers that addressed the many gaps in our understanding of PKD. Examples of progress made by these centers include: improved animal models of disease due to increased understanding of the underlying molecular processes that result in cyst formation and growth; progress in understanding the role of the primary cilium in kidney tubule cyst formation; and the development of prediction models based upon kidney imaging.

Despite this progress, many challenges remain in determining other genetic and pathophysiologic mechanisms of PKD that could potentially be targeted for therapeutic interventions. Recognizing the need for interdisciplinary, integrated approaches for identification of novel therapies, this FOA is issued to support the PKD Research and Translational Core Centers (RTCCs) to support development of innovative resources for the wider research community. Concomitantly, a FOA (RFA-DK-19-011) is issued to support a Central Coordinating Site to provide centralized administrative support to the RTCCs. The RTCCs are expected to work collaboratively with the CCS as part of the PKD Research Consortium.

Objectives and Scope

The goal of the PKD Research Consortium is to create a framework for collaboration that develops and broadly shares research resources, core services and expertise to support innovation in research related to PKD. The RTCCs will develop and share research resources (e.g. data, samples, tissues, reagents, technologies, tools, software, animal models, etc.), core services (e.g. genotyping) and expertise that would be difficult or impractical to support in individual labs. All activities within the PKD Research Consortium are expected to address the overall goal of improving our understanding of the pathogenesis, progression, prevention and clinical management of PKD through enhanced sharing of research resources, core services and expertise to ensure the establishment of a robust research community. The RTCCs will be awarded to institutions with a strong track record of funded research in PKD that demonstrate a plan to engage new and established investigators including those from outside the traditional areas of PKD research. An RTCC may be located at a single institution or may span multiple institutions with complementary research bases. All RTCCs are expected to work collaboratively with other RTCCs within the PKD Research Consortium, the Central Coordinating Site and NIDDK program staff to achieve the goals of the program. It is expected that all resources developed by the RTCCS will be made available as soon as quality control procedures have been completed at the local institution and be rapidly shared with the broader research community. RTCCs which include a Clinical/Translational Biomedical Research Core will work with other sites in the PKD Research Consortium to devise a unified approach to PKD patient evaluation, novel phenotyping, data collection, and data and image sharing to make the best use of participants.

Project Organization

The PKD Research Consortium will consist of up to four RTCCs and a Central Coordinating Site (CCS). Individual RTCCs, directed by the RTCC Director must include an Administrative core and at least two Biomedical Research Cores. An RTCC must be an identifiable organizational unit within a university or a defined consortium of cooperating institutions. The CCS will coordinate communications between the PKD Research Consortium and the greater research community, organize and facilitate the education and outreach activities of the Consortium and support and administer the Pilot and Feasibility Program. Applications for CCS are solicited through a separate, companion FOA (RFA-DK-19-011). Investigators with appropriate expertise may apply to both RFA-DK-19-010 and RFA-DK-19-011. Potential applicants are encouraged to contact the Program Official named in Section VII to discuss their potential applications.

The coordinated efforts of the RTCCs and the CCS will be overseen by PKD Research Consortium Steering Committee composed of RTCC Directors, the CCS Director, and NIDDK program staff. The PKD Research Consortium will meet at minimum once yearly for a face-to-face meeting in the Bethesda, MD area that will be coordinated by the CCS. The first meeting will be held September 14, 2020 and all RTCC Directors, Biomedical Research Core Directors and the CCS Director are required to attend. The NIDDK will utilize an External Experts Panel (EEP) to monitor research efforts and advise the Institute on the progress of the PKD Research Consortium.

Administrative Core

The Administrative Core will serve as the primary managerial component for all activities of the RTCC, including communication with the CCS. It will be responsible for the management of resources within the RTCC to ensure success in the integrated activities of the RTCC and to collaborate with the CCS in meeting the goals of the PKD Research Consortium.

Key responsibilities of the Administrative Core are to:

• Establish access to and monitor use of each Biomedical Research Core.
• Create mechanisms for internal monitoring and planning, including for RTCC budget and personnel considerations.
• Establish and maintain internal communication and cooperation among all RTCC investigators, the larger PKD Research Consortium, the CCS, outside research community, and the NIDDK.
• Work with the CCS to execute Material Transfer Agreements (MTA) between the CCS, other RTCCs and investigators outside of the PKD Research Consortium.
• Administer the Summer Student Enrichment Program.
• Develop reports on RTCC activities and progress for external review.
• Identify fixed and variable costs and establish procedures for negotiation of third party agreements or selection of subawards/subcontractors (i.e. clinical/research laboratories, biospecimen repositories, etc.) with involvement of NIDDK Technology Advancement Office, and develop processes to efficiently administer and manage same throughout the project.

Biomedical Research Core

The Biomedical Research Cores are defined as highly innovative, shared resources that provide specialized and essential services, techniques, or instrumentation to PKD Research Consortium investigators and the outside community, allowing studies to be conducted more efficiently and effectively. The Biomedical Research Cores thus must demonstrate utility as a national resource for supporting PKD research within and outside the PKD Research Consortium. Biomedical Research Cores headed by investigators from outside the PKD research community are strongly encouraged.

Examples of types of Biomedical Research Core resources may include, but are not limited to:

• Provision of specialized tools and technologies or access to specialized expertise
• Development, standardization and distribution of antibodies, cells, organoids, animal models and/or protocols
• Development, beta-testing and dissemination of specialty assays, methods, and services
• Provision of models for high throughput screening of promising new therapeutic targets for PKD
• Development of mathematical models to identify novel pathways in the pathogenesis of PKD
• Recruitment, retention and evaluation of PKD patients using novel methods of phenotyping and a unified, consortium-wide approach
• Collection and sharing of clinical data, protocols, biological samples and imaging.

The National Center for Advancing Translational Sciences (NCATS) currently supports a national network of medical research institutions, i.e. hubs, via Clinical and Translational Science Awards (CTSA), which provide services and resources to enhance clinical research (https://ncats.nih.gov/ctsa). The Biomedical Research Cores supported by the NIDDK are encouraged to collaborate with CTSAs and should not overlap effort or services.

Research and Translation Core Center (RTCC) Director

The RTCC Director must be an established investigator with demonstrated research accomplishments in PKD and who can provide effective administrative and scientific leadership. RTCC Director should demonstrate prior success in obtaining external funding. The RTCC Director is expected to work closely with the CCS, other RTCCs and the NIDDK, including through participation on the PKD Research Consortium Steering Committee, regular teleconference calls and at relevant meetings and workshops supporting the PKD Research Consortium goals. One or more Associate Directors may be named. The RTCC Director will be responsible for scientific and administrative leadership. This includes, but is not limited to, the following duties:

• Maintaining the RTCC’s vision and ensuring the relevance of the RTCC’s goals to NIDDK mission interests in PKD.
• Oversight of the Administrative Core and the Biomedical Research Cores.
• Ensuring productivity, internal communication and cooperation among RTCC investigators, including performance of all personnel.
• Ensuring equitable access to RTCC resources across the PKD Research Consortium and the wider research community
• Communicating with the larger PKD Research Consortium, NIDDK Program Staff and the outside research community.

SeeSection 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 from 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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the 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.
• o 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.

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.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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)
Telephone: 301-594-7797
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall (for Center Overview)	6
Admin Core	12
Core (use for each Biomedical Research Core)	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: Required (Minimum: 1, Maximum: 1)
• Admin Core (use for Administrative Core): Required (Minimum: 1, Maximum: 1)
• Core (use for Biomedical Research Core): Required (Minimum 2)

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Other Attachments:

Statement of Willingness: Please title this attachment "Willlingness to Participate" and provide a statement indicating a willingness to:

Work with NIDDK and the PKD Research Consortium to participate in the initial and annual meetings thereafter during the course of the grant award;

Cooperatively interact with NIDDK and PKD Research Consortium in support of the projects and activities;

Actively seek input from NIDDK and the PKD Research Consortium regarding resource or expertise needs that may arise during the performance of the project;

Develop and execute Material Transfer Agreements to permit sharing of biological specimens, molecules, cells, animals, genetic material, de-identified patient samples, de-identified patient data and imaging;

Participate in monthly conference calls

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

Budget must include costs for the Research Core Center Directors, Associate Director and at least one other member of the project to attend the annual, in-person meetings.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: State the overall goals of the RTCC and their significance to PKD research. Summarize the general approach, the types and purposes of research resources and service cores to be generated, their expected value and the impact of the resources and outcomes to achieving the goals of the PKD Research Consortium as outlined in Section I. Funding Opportunity Description.

Research Strategy: Describe the major themes, goals, and objectives of the RTCC, including any background information. List the individual components of the RTCC (Administrative Cores and Biomedical Research Cores) and explain their overall importance and contributions and how they will interact collaboratively to achieve the goals and objectives of the PKD Research Consortium as outlined in Section I. Outline the existing skills and technologies available at the RTCC as well as other resources that will be developed. Describe how the RTCC will create opportunities for investigators within and outside the PKD research field, and promote collaborations leading to advances in PKD research. Describe how the RTCC will engage new and established investigators including those from outside the traditional areas of PKD research.

Describe the overall scientific and administrative framework of the RTCC. Include an organizational chart. Note research and/or administrative leadership of RTCC personnel. Provide a leadership plan for oversight and operations of the overall RTCC, including conflict resolution for Center personnel. Provide a brief description and rationale for any proposed collaborations or additional consultants. Include information on the support and commitment of the parent institution for the RTCC, and the authority of the PD(s)/PI(s). Include description of any cores/services to be utilized through the CTSA and address any potential overlap with cores/services proposed by the RTCC.

Letters of Support: Include all assurance letters including institutional commitments and outside collaborations, if such plans are listed in application. The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).

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 modifications:

• All applications should include a Data Sharing Plan.
• All applications are expected to provide plans that address sharing and demonstrate commitment to making resources, models, reagents, tools and methods available to the PKD Research Consortium and the broader research community. The terms and timelines for sharing within the PKD Research Consortium, validation of models and methods and sharing with the broader research community will be established by the Steering Committee in a manner consistent with achieving the goals of the program and NIH policies. All participants are expected to adhere to these terms as a condition of award.
• Applicants should include in their data sharing plan the assurance that resources 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.
• Applicants are expected to register resources supported by this FOA with the NIDDK Information Network (dkNET) at https://dknet.org/ and use Research Resource Identifiers (RRID) assigned through dkNET in any publication supported by this FOA

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Administrative Core Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. The overall Research Core Center Director will serve as the Administrative Core Director

Budget forms appropriate for the specific component will be included in the application package.

The overall RTCC Project Director/Principal Investigator will serve as the Director of the Administrative Core and will oversee all scientific and administrative activities of the RTCC. Support for the RTCC Director should be provided within the budget of the Administrative Core. The minimum level of effort for the RTCC Director (as Administrative Core Director) is 1.2 person months (10%). Administrative Core Associate Directors may be named as well, but the total, combined Administrative Core Directorship efforts may not exceed 1.8 person months (15%). The Administrative Core may also include an administrative assistant(s), if justified.

The Administrative Core budget must include at least $25,000 of direct costs every year specifically devoted to supporting a summer student enrichment program. The Administrative Core Budget will support the activities outlined in Section I, including travel of investigators to learn new laboratory techniques, develop new collaborations, or engage in scientific information exchange. The Administrative Core budget must include funds to support travel of the RTCC Director, Biomedical Research Core Directors and key personnel, to attend the inaugural meeting of the PKD Research Consortium to be held in Bethesda, MD on September 14th, 2020. Additionally, the Administrative Core budget must include funds to support yearly travel of the RTCC Director, Biomedical Research Core Directors and key personnel, including any junior investigators for an additional 3-day face-to-face annual meeting of the PKD Research Consortium.

Budget Justification: Describe the specific functions of all key personnel, consultants, collaborators, and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For years 2-5 of support requested, justify any significant increase or decrease in any category over the initial budget period. Identify such changes with asterisks against the appropriate amounts.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Clearly state how the Administrative Core will set the overall direction of the RTCC, ensure optimal utilization of RTCC resources and work with the CCS to promote collaboration within and across the RTCCs

Research Strategy: The goals of the Administrative Core are to develop and maintain the vision and relevant goals of the RTCC; coordinate, manage, and integrate the RTCC’s components and activities, which includes coordinating ongoing research between Biomedical Research Cores, harmonizing with the other RTCCs within the PKD Research Consortium and collaborating with NIDDK. In addition, the Administrative Core is responsible for carrying out the Summer Student Enrichment Program.

Describe the strategy by which the Administrative Core will effectively lead, organize, and provide (1) fiscal and resource management for the RTCC; (2) management of the Biomedical Research Cores; (3) coordination of research efforts within the RTCC, the CCS, the NIDDK, and with the broader research community. Indicate who will be responsible for these activities. Describe strategies for building and maintaining a functioning multi- and inter-disciplinary team (bringing scientists out of their research silos).

Describe the relationship and lines of authority and sanction by appropriate institutional officials. Include plans for development and execution of Material Transfer Agreement between the RTCC institution and outside investigators as indicated in Overall Component.

In addition, outline the approaches to be utilized for (1) internal monitoring, including RTCC operations management, fiscal administration, personnel management, planning, budgeting, and other appropriate capabilities; (2) establishing and maintaining internal communication and cooperation among RTCC investigators; and (3) reviewing productivity and effectiveness of RTCC activities, conflict resolution, and improving or terminating ineffective RTCC Cores.

Describe how the Summer Student Enrichment Program will be administered.

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: Applicant may state that the Data Sharing Plan outlined in the Overall Component applies to the Core.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Core.

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

SF424 (R&R) Cover (Biomedical Research Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Biomedical Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Biomedical Research Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Biomedical Research Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Biomedical Research Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Administrative Core Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. The overall Research Core Center Director will serve as the Administrative Core Director

Budget (Biomedical Research Core)

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

A Biomedical Research Core Director should be named and is expected to contribute a minimum level of effort of 0.6 person months (5%). One or more Associate Directors may also be named. The salary amount charged to the Biomedical Research Core must be commensurate with the time spent on Core activities and is subject to institutional and NIH salary policies. A Biomedical Research Core Director with requisite expertise may devote a greater effort to the core. Salary support for technicians and other core personnel are allowable in accordance with the volume and type of work in the core. Stipends (and tuition) for research trainees (e.g. graduate students, postdoctoral fellows) are not available through Biomedical Research Cores.

Budget Justifications: Describe the specific functions of all Biomedical Research Core key personnel, consultants, collaborators and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For years 2-5 of support requested, justify any significant increases or decreases in any category over the initial budget period. Identify such changes with asterisks against the appropriate amounts.

PHS 398 Research Plan (Biomedical Research Core)

Specific Aims: Describe the major function, capability, and objectives of the Biomedical Research Cores

Research Strategy: A Biomedical Research Core must function as a highly-innovative, shared resource that provides specialized and essential services, techniques, or instrumentation to the RTCC, to the PKD Research Consortium and to the wider PKD research community. The capacity for the Biomedical Research Cores to serve as a national resource for the larger PKD community should be described with sufficient allocation of resources.

Describe the purpose and objectives of the Biomedical Research Cores and its administration, organization, and operations. Include a description of services provided and their significance to accomplishing the scientific goals of the PKD Research Consortium, plans for quality control, and how it will adapt to new technology and to the needs of the RTCC members. Describe how access to the Biomedical Research Cores by RTCC investigators and the larger PKD research community will be prioritized, operationalized, and any fee structure.

Describe the novelty of services and resources generated and offered by the Biomedical Research Cores. For a Biomedical Research Core that by its nature is not innovative, describe how it is essential to advance the field. Describe the potential for interdisciplinary collaborations among RTCC investigators.

Describe how leveraging existing resources will is considered, particularly when this provides a range of services or efficiency that would not otherwise be available. Furthermore, applicants should demonstrate that support for the existing resource through the PKD RTCC provides added value to the resource beyond that which would be provided by paying for use of the resource through a fee for service. Applicants from institutions that have a CTSA funded by the NIH may wish to identify the CTSA as a resource for conducting the proposed research, if appropriate.

Provide a description of how the Biomedical Research Cores contribute to the goals of the Administrative Core and the overall RTCC. In addition, provide the following information:

Brief description of the Biomedical Research Core scientific, technical, and support staff functions.

Provide a description of how the Biomedical Research Cores contribute to the goals of the Administrative Core and the overall RTCC. In addition, provide the following information:

a) Brief description of the Biomedical Research Core scientific, technical, and support staff functions.

b) Provide a summary of projected usage of Core services (e.g., assays performed, animals supplied, etc.) by the RTCC team or other users, including PD/PI, name of grant, and funding source.

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: Applicant may state that the Data Sharing Plan outlined in the Overall Component applies to the Core.

PHS Human Subjects and Clinical Trials Information (Biomedical Research Core )

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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.

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

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

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the PKD RTCC 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 PKD RTCC 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 PKD RTCC that by its nature is not innovative may be essential to advance a field.

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

Specific to this FOA: How will this RTCC support the broader PKD research community?

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

Specific to this FOA: Is appropriate multi- or interdisciplinary expertise represented to achieve the goals of the RTCC?

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

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

If the PKD RTCC involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: How will the RTCC create opportunities for investigators new to PKD research? How will the RTCC promote collaboration within the applicant institution and the larger research community? Are the responsibilities of all personnel and the lines of communication clearly established?

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

Specific to this FOA: Is there evidence of institutional commitment to the PKD Research and Translation Core Center such as space, protected time, and/or financial support? Is there a suitable environment for RTCC interactions and cross-fertilization with scientists from other areas of expertise?

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.

Center Integration

Specific to this FOA: The overall Research Center will also be evaluated as an integrated research effort focused on the PKD research mission of the NIDDK. The relationship and contributions of each proposed Biomedical Research Core(s) to the overall Research Center goals will be evaluated and contribute to the overall impact score. This assessment will consider the following:

Will there be coordination, interrelationships, and synergy among the Administrative Core and the Biomedical Research Cores within the PKD Research Consortium through the Coordinating Center Site?

If proposed, is there strong justification for a multi-institution Research Center?

Are mechanisms proposed for regular communication among the Program Director, Administrative Core Leader, Biomedical Research Core Project Leaders within the Center and the PKD Research Consortium?

Are the administrative structures in place for daily management of the Research Center, including oversight of the Biomedical Research Cores?

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

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

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

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

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

Not applicable.

Not applicable.

Not applicable.

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

Not applicable.

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

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

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Core 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 Core 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, an Administrative Core that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed Core address the needs of the research program that it will serve? Is the scope of activities proposed for the Core appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research program?

Investigator(s)

Are the Core leader(s) and other personnel well suited to their roles in the Core? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing genitourinary research? Do the investigators demonstrate significant experience with coordinating collaborative basic and/or clinical research? If the Core is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Core? Does the applicant have experience overseeing selection and management of subawards, if needed?

Innovation

Does the application propose novel organizational concepts in coordinating the research program the Core will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research program the Core will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the program is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the program? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this FOA: Are there a clear plan and timeline to work with applicant institution to develop and execute a Material Transfer Agreement? Is the strategy for summer student enrichment program well-developed and appropriate?

Environment

Will the institutional 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 institutional environment, infrastructure, or personnel? Are resources available within the

scientific environment to support electronic information handling?

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.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not applicable.

Renewals

Not applicable.

Revisions

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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).

Resource Sharing Plans

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 .

Authentication of Key Biological and/or Chemical Resources

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.

Budget and Period of Support

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Biomedical Research Core 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 Core proposed).

Scored Review Criteria - Biomedical Research Core

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 Biomedical Research Core that by its nature is not innovative may be essential to advance a field.

Significance

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

Specific to this FOA: Does the Biomedical Core(s) demonstrate innovation and high value contributions beyond what has been conventionally used in PKD research?

Investigator(s)

Are the Core Director(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the Core 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?

Innovation

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

Specific to this FOA: Do the techniques, methods or expertise in this Biomedical Research Core represent a novel approach that has not previously been used in the PKD research field?

Approach

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

If the Core involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Is there a clear plan that describes how the Biomedical Research Core resources will be made available to the other RTCCs in the PKD Research Consortium and to the wider PKD research community?

Environment

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?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not applicable.

Renewals

Not applicable.

Revisions

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.

Applications from Foreign Organizations

Not applicable.

Select Agent Research

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).

Resource Sharing Plans

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 .

Authentication of Key Biological and/or Chemical Resources

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.

Budget and Period of Support

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 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 the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. 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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• Accountability towards the applicant organization officials and to the NIDDK for the performance and proper conduct of the research supported by the project in accordance with the terms and conditions of the award.
• Serving as a voting member of the PKD Research Consortium Steering Committee and attending the initial meeting which will serve as a planning meeting, the annual meeting, and monthly teleconference calls.
• Accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee, and be responsible for close coordination and cooperation with the components of the PKD Research Consortium with NIH staff.
• Adhering to PHS policy for the distribution of unique research resources produced with PHS funding as described under Resource Sharing. The NIH Project Scientist, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as other members of the Steering Committee.
• The PI is expected to put all study design materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NIDDK, for the conduct of research at no charge other than the costs of reproduction and distribution, consistent with achieving the goals of this program initiative.
• 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.
• Any third-party (including industry, academia, and foundations) collaboration should be governed by a research collaboration agreement (e.g. Clinical Trial Agreement, Research Collaborative Agreement, Memorandum of Understanding, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures, and with written approval from NIDDK Program and other staff (including Technology Advancement Office).
• Any involvement of a third party (including industry, academia, and foundations) in the study, including access to any study data or study results not already publicly available; using the name of the study; or the name of the NIH or NIDDK, is permitted only after written concurrence by the NIDDK Program staff who may consult with others at NIH including the NIDDK Technology Advancement Office.

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

• NIH Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. However, the dominant role and prime responsibility for the project as a whole resides with the awardees, although specific tasks and activities in carrying out the studies will be shared by awardees and the NIDDK.
• NIDDK will designate a Project Officer and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement.
• NIDDK will form an External Evaluation Panel (EEP), comprised of the NIDDK Project Scientist(s) and other NIH extramural staff with relevant scientific expertise or who manage research grant programs that relate scientifically to the goals of the PKD Research Consortium, and outside advisors selected by the NIDDK. The EEP will meet annually with the PKD Research Consortium Steering Committee to review and assess the Consortium and to advise NIDDK Project Staff of scientific developments and opportunities that may enhance the achievement of the PKD Research Consortium goals.
• NIDDK Project Scientist(s) will attend and participate as a voting member in all meetings of the Steering Committee and provide liaison between the Steering Committee and the EEP.
• NIDDK Project Scientist(s) will help the Steering Committee develop and draft operating policies.
• The NIDDK Project Officer will review the scientific progress of the PKD Research Consortium for compliance with operating policies developed by the Steering Committee, and may recommend to the NIDDK to withhold support, suspend, or terminate an award for lack of scientific progress or failure to adhere to policies established by the Steering Committee.

Areas of Joint Responsibility include:

• Steering Committee - The NIH Project Scientist, PIs from projects funded through this FOA and RFA-DK-19-011, will be responsible for forming a Steering Committee as defined below. An arbitration system, as detailed below, will be available to resolve disagreements among members of the Steering Committee. The Steering Committee will be the main governing board of the PKD Research Consortium. It will develop collaborative protocols, identify technological impediments to success and strategies to overcome them, develop shared software tools for disseminating information about the projects, and identify opportunities for sharing techniques and tools that might be developed in future projects.
• The PIs and NIDDK Project Scientist(s) will each have one vote on the Steering Committee. The Steering Committee will select a chairperson who will be someone other than an NIH staff member.
• The Steering Committee may, as it deems necessary, invite additional, non-voting scientific advisors to meetings at which research priorities and opportunities are discussed. The NIH reserves the right to augment the scientific or consumer expertise of the Steering Committee when necessary.
• There will be one face-to-face Steering Committee meetings annually, with the exception of year one, where there will be two. Additional periodic steering committee meetings will be held via web conference. The first meeting will be held on September 14, 2020. At this initial meeting, the Steering Committee will be formed, and a chairperson selected from among the members. At this meeting, the Steering Committee may: (a) draft a charter to detail policies and procedures, a process for monitoring compliance with the policies and procedures, and a process for recommending that the NIH Project Administrators act on evidence of non-compliance of any Consortium component with Steering Committee policies; and (b) agree upon the terms of the charter; and (c) devise a plan for working with the Central Coordinating Site to provide input into website design and database content.
• At the second and subsequent meetings, the Steering Committee will refine the PKD Research Consortium projects' scientific objectives and implementation as necessary.
• The Steering Committee will plan workshops, to which non-PKD Research Consortium participants will be invited, in order to inform the research community of the progress made by the PKD Research Consortium toward meeting its' goals, and to inform the research community of any technological advances related to PKD Research Consortium. The NIDDK Project Scientist, the EEP, and other NIH staff as appropriate will provide the Steering Committee with advice on participants for the workshops and symposia.
• The Steering Committee may establish subcommittees as it deems appropriate; the NIH Project Scientist may serve on the subcommittees as deemed appropriate.
• Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
• The EEP will meet annually with the PKD Research Consortium Steering Committee to review and assess the progress of the PKD Research Consortium and to advise NIDDK Project Staff of scientific developments and opportunities that may enhance the achievement of the PKD Research Consortium goals.

Dispute Resolution

Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIDDK may be brought to dispute resolution. A dispute resolution panel will be composed of three members --one selected by the awardee (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIDDK, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR 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 RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Christine Maric-Bilkan, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-0486
Email: [email protected]

Susan R. Mendley, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-8?2?7-1861
Email: [email protected]

Xiaodu Guo, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-?5?9?4-4719
Email: [email protected]

Krystle Nicholson
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8860
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.