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

Despite advances in the clinical management of many genitourinary conditions, millions of Americans remain afflicted with benign conditions of the bladder and urogenital system, including urinary tract infections, urolithiasis, conditions associated with lower urinary tract symptoms such as urinary incontinence, over- and underactive bladder and bladder outlet obstruction, urologic chronic pelvic pain syndrome, and erectile dysfunction. The annual treatment cost of these illnesses is at least $11.5 billion per year. Contributing to the inability to adequately treat patients are the gaps in knowledge of the basic physiology, cell biology, and genetics of normal and abnormal urologic function; a lack of objective diagnostic criteria and tests for many benign genitourinary symptoms and conditions; inadequate in-depth characterization (phenotyping) of patients; and the paucity of epidemiological insights. This absence of a basic understanding of the mechanistic changes of the urogenital tract in disease also makes it difficult to establish clinically-relevant models of genitourinary conditions.

The O'Brien Urology Research Centers Program was established by the NIDDK in 1987 to support stand-alone Research Centers to address the many gaps in our understanding of genitourinary dysfunction. In 2012, the program was transitioned to a Cooperative Research Centers Program (U54). The transition was prompted by a recognized need for more highly-interdisciplinary, integrated approaches within and between Research Centers and to support development of new research resources for the wider benign genitourinary research community. This strategy includes an emphasis on engaging broad expertise beyond traditional urology clinical and basic science.

The O Brien Urology Cooperative Research Centers Program fosters broad basic, translational, and clinical research on questions of critical importance; develops research resources to support the larger urology research community; engages new and established investigators from urology and other clinical and research disciplines; and promotes the training of junior scientists electing to conduct research in the field of benign genitourinary conditions. The O Brien Centers Program works cooperatively with the NIDDK Developmental Centers for Interdisciplinary Research in Benign Urology (P20), the NIDDK Urologic Research (KURe) Career Development Program (K12), and the Urological Epidemiology (UroEpi) Institutional Research Career Development Program. All efforts are designed to improve prevention and clinical management of genitourinary conditions within the research mission of the NIDDK. Through addressing these broad, critical goals, O Brien Urology Cooperative Research Centers are viewed as centers of excellence for the genitourinary research and clinical communities. The long-term strategy for the O Brien Urology Cooperative Research Centers Program is expected to continue to evolve in future years to best support the urologic community and foster development of high-quality, successful investigator-initiated research studies and applications (e.g., R01s).

Research Centers

O Brien Urology Cooperative Research Centers address critical questions related to proper urologic function and benign genitourinary conditions relevant to the NIDDK’s mission. Research Centers address these questions through rigorous and high-impact scientific investigations designed to provide significant advances in the genitourinary field. Research Centers also provide unique opportunities for developing and sharing research resources; engaging new and established investigators from urology and other disciplines to foster a robust research community; and collaboration within the Program, with other NIDDK urology research and training efforts, and with the broader community. Research Center investigators are additionally expected to promote collaboration and research excellence through participation in relevant O Brien Urology Research Centers Program Committees and through interactions with relevant NIDDK Program Staff. In addition, Research Center leadership and relevant investigators are expected to actively participate in regular O Brien Cooperative Urology Research Centers Program teleconferences and in-person meetings. To foster true centers of excellence, it is anticipated all components will be within a single institution.

Research Center components will include:

• Two or more Research Projects
• Administrative Core, which includes Educational Enrichment and Opportunity Pool Programs
• One or more Biomedical Research Cores

NOTE: In addition to the Administrative Core, a viable Research Center would require a minimum of three highly meritorious components (i.e., two Research Projects and one Biomedical Research Core as a minimum).

Research Projects

Research Projects conduct cutting-edge scientific investigations designed to provide critical, new information on underlying mechanisms and phenotype and inform on risk factors and the clinical diagnosis, treatment, and prevention of benign genitourinary disorders relevant to the NIDDK mission. Each Research Project proposed should have a named Project Leader. A minimum of two Research Projects are required for a Research Center, but more may be proposed.

Collectively, at least two of the following approaches must be represented within the overall scope of the Research Center's Projects: 1) clinical studies, 2) translational research using fundamental observations that inform clinical studies and management (or vice versa), and 3) basic science studies of underlying disease mechanisms. Studies should be designed to address questions relevant to the health of both males and females, unless a strong justification can be provided why only one sex is considered.

Research projects are encouraged to leverage insights and available resources from other NIDDK-sponsored studies, including data and biological samples available through the NIDDK’s Central Repository (https://repository.niddk.nih.gov/home/). Studies with particular relevance include, the Urological Diseases in America (UDA) Project, the Boston Area Community Health (BACH) Survey, Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial, Urinary Incontinence Treatment Network (UITN), the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, the Lower Urinary Tract Dysfunction Research Network (LURN), and the GenitoUrinary Development Molecular Anatomy Project (GUDMAP).

Cutting-edge scientific investigations of the following are considered high priority, though this list is not exclusive.

• Male and female Lower Urinary Tract Symptoms (LUTS), including the lower urinary tract and pelvic floor basis of urinary incontinence, overactive bladder, underactive bladder, and bladder outlet obstruction.
• Urinary Tract Infections, including contributions of host-biology and bacterial-host interactions.
• Urolithiasis, including stone formation, the contributions of the microbiome, and improved methods for detection and dissolution of stones.
• Conditions involving benign prostatic tissue changes (e.g. glandular hyperplasia, stromal hypertrophy, inflammation, and fibrosis).
• Urologic Chronic Pelvic Pain Syndrome (UCPPS), including observational studies, development of clinical sub-grouping strategies, development of model systems with improved translational relevance, and the relationships between UCPPS and associated disorders.
• Erectile Dysfunction, including identification of new interventional targets for development of novel therapies.
• Kidney and urologic stone disease, including assessments of associated LUTS.
• Congenital Genitourinary Malformations, including observational studies to explore potential risk and protective factors and development of clinically relevant model systems.

Studies addressing the above may incorporate questions and approaches ranging from basic, translational, and/or clinical. These may include (but are not limited to), fundamental molecular and cellular biology and pathophysiology; epidemiology and risk factors; neurobiology; genetics; identification of new therapeutic targets; and insights informing prevention, treatment, and development of improved diagnostics and symptom measurement tools to support therapy selection and assessment of efficacy.

Applications based on a cross-cutting theme, such as regenerative medicine, genitourinary complications of diabetes and/or obesity, omics of the urine, the contribution of the microbiome, among other examples, are appropriate, but must lead to an in-depth understanding of one of the above or related concepts or conditions. Studies addressing the physiological interplay between genitourinary organs/tissues and how this may lead to symptom development are highly encouraged. Integrated, synergistic research designs that seek to correlate multiple scientific domains, both basic and clinical, to provide an improved and more comprehensive assessment of specific aspects of the urologic system or patient phenotype in health and disease are also highly encouraged, as are studies with significant translational potential to inform on clinical management (prevention and treatment) and the development of future, evidence-based clinical studies/trials.

Applications proposing studies addressing malignant genitourinary diseases or biological changes primarily effecting the kidney in the absence of relevance to clinical urologic considerations are not responsive to this FOA and will not be reviewed.

Administrative Core

The Administrative Core broadly supports Research Center operations to foster the diverse, integrated activities of the Center and address the goals of the O Brien Cooperative Research Centers Program. This includes promoting resource sharing and productive interactions with the larger O Brien Program and cooperating programs, the outside community, and the NIDDK. The Administrative Core also directs the Research Center’s Educational Enrichment and Opportunity Pool Programs.

Key responsibilities of the Administrative Core are to:

• Ensure adherence to the overall goals of the Research Center and O Brien Cooperative Research Centers Program.
• Coordinate, manage, and integrate the Research Center components and activities, which include coordinating ongoing research between the Research Projects and the Biomedical Research Core (if proposed).
• Create mechanisms for internal monitoring and planning, including for Research Center budget and personnel considerations.
• Establish and maintain internal communication and cooperation among all Research Center investigators, the larger O Brien Cooperative Research Centers Program, the outside community, and the NIDDK.
• Tracking and documenting collaborative interactions, dissemination of research findings, and sharing of research resources with the broader research community.
• Review productivity and effectiveness of Research Center activities and create a mechanism for addressing deficits, including selecting and replacing Center personnel or changes in research strategy.
• Develop reports on Research Center activities and progress for external review.
• Develop, administer and maintain oversight of Educational Enrichment Programs.
• Administer and maintain oversight administer funds dedicated to the Opportunity Pool Program.

Educational Enrichment Program: The Educational Enrichment Program may consist of seminar series, guest lectures, summer student experiences (at the high school, college, and graduate or medical student level), symposia, workshops, or other activities that educate Research Center members and the research community on how to develop and conduct sound research studies and how to utilize available databases or other resources. Students, fellows, and junior faculty should be encouraged to take full advantage of all Educational Enrichment Program events. Research Center Institutions may collaboratively develop and support Educational Enrichment activities. Support to attend meetings or engage in a research experience outside of an individual’s discipline is encouraged.

The Opportunity Pool Program: The Opportunity Pool Program seeks to encourage interactions between Research Center investigators, the NIDDK KURe (K12) fellows, investigators of the NIDDK Developmental Planning Centers (P20s), and/or the larger research community. A goal of the Opportunity Pool Program is to increase the capacity of the urology research community by leveraging the resources within the Research Centers. Although funds are not provided directly for training purposes, the Opportunity Pool Program may provide support of investigators to learn new laboratory techniques, develop new collaborations, or engage in scientific information exchange in support of the project.

Opportunity Pool Program activities should be integrated into the overall research goals of a Research Center and where possible make use of the resources provided by the Center’s Biomedical Research Core. Opportunity Pool projects are limited to (a) early stage investigators or (b) established investigators not previously involved in genitourinary research. Projects may represent new collaborations with current Research Center investigators. O'Brien Centers will identify appropriate Opportunity Pool candidates and solicit applications from within the Center's academic organization and from the larger research community. The Opportunity Pool program is not intended to support or supplement ongoing research of an established genitourinary investigator. It is expected that Opportunity Pool projects will generate preliminary data to support future research applications, such as NIH investigator-initiated R01s and may serve to pilot test high-risk/high-reward concepts. Research investigating the relationships between biological and clinical characteristics are encouraged. Opportunity Pool research projects are limited to $100,000 direct costs per year and are initially two years with an option to extend the project an additional year pending exceptional progress.

It is expected that each Research Center will be associated with 2-3 Opportunity Pool research projects at any given point in time. Funds for the Research Center’s Opportunity Pool Program should be requested as part of the Administrative Core’s budget and will be restricted to sole support of the Program. Research Center Institutions may develop and co-fund joint Opportunity Pool Program activities. Opportunity Pool proposals will be assessed by independent content experts selected by the NIDDK. These experts will provide comments on scientific merit for submitted Opportunity Pool applications to the NIDDK. The NIDDK is responsible for making final award decisions based on review, the availability of funds, and the O Brien Cooperative Research Centers goals and interests. Recommendations from the program’s External Experts Panel will be solicited, as needed.

Biomedical Research Core

One or more Biomedical Cores must be proposed. The Biomedical Core is defined as a highly innovative, shared resource that provides specialized and essential services, techniques, or instrumentation to Research Center investigators and/or the outside community allowing studies to be conducted more efficiently and effectively. A proposed Biomedical Core must be used by one or more of the parent Research Center’s Research Projects and must support the overall goal of providing a national resource for the urologic community.

The Biomedical Research Core should be accessible to and should increase interactions between other O'Brien Cooperative Research Centers, the NIDDK Urologic Research (KURe) Career Development Program (K12), the NIDDK Developmental Centers for Interdisciplinary Research in Benign Urology (P20) Program, and the broader research community through cross-project/laboratory exchange, and sharing of specialized tools, technologies. In this way Biomedical Research Cores must have utility as a national resource for supporting genitourinary research within and outside the O Brien Cooperative Research Program.

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

• Analysis, storage and distribution of data and samples.
• Provision of specialized tools and technologies or access to specialized expertise.
• Development and validation of self-reported measures to better assess genitourinary symptoms.
• Development, standardization and distribution of reagents and/or protocols.
• Coordination and monitoring of recruitment of study participants and collection of clinical data and biological samples.
• Development, beta-testing and dissemination of specialty assays, methods, and services.

Biomedical Cores with demonstrated innovation and high value beyond conventional technical contributions typically found at a research institution will be prioritized.

Research Center Director

The Research Center Director must be an established investigator with demonstrated research accomplishments and prior success in obtaining external funding. Prior research accomplishment or funding specific to urology is not required. The Center Director is expected to work closely with the larger O Brien Cooperative Research Centers Program and the NIDDK, including through participation on committees and regular teleconference calls and at relevant meetings and workshops supporting the program goals. One or more Associate Directors may be named. The Research Center Director and Associated Directors may be from any discipline. The Research Center Director will be responsible for scientific and administrative leadership. This includes, but is not limited to, the following duties:

• Maintaining the Research Center’s vision and ensuring the relevance of the Center’s goals to NIDDK mission interests in benign genitourinary disorders
• Ensuring internal communication and cooperation among Research Center investigators, and O Brien Center Interactions Core.
• Oversight of the Administrative and Biomedical Research Cores, including the Education Enrichment and Opportunity Pool Programs
• Internal monitoring to ensure efficient and productive Research Centers operations, including performance of all personnel
• Representing the Research Center at meetings of external oversight groups and the NIDDK
• Communicating with the larger O Brien Cooperative Research Centers Program, NIDDK Program Staff, and associated NIDDK Programs, and the outside research community
• External Advisory Committee.

The use of an External Advisory Committee (EAC) for each Research Center is highly recommended. Proposed members must not be named in the grant application; however, the process by which members are selected should be detailed. The EAC may advise the Research Center in areas of scientific direction, budget, policy, collaboration, or other, as needed.

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

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

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

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

The Center Director is required to have an established record of external funding and research accomplishment but is not required to have a background in genitourinary research. The Center Director may not serve concurrently as the Center Director of a NIDDK George M. O'Brien Urology Cooperative Research Center (U45) and as a PD/PI for a NIDDK Urology Developmental Center (P20). However, current P20 PDs/PIs are eligible to apply for an NIDDK George M. O'Brien Urology Cooperative Research Center (U54) with the expectation that support from the P20 would terminate upon receipt of the U54 award.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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: NIDDKLetterofintent@mail.nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	6
Administrative Core	12
Biomed Research Core (use for each Biomedical Research Core)	6
Research Project (use for each Research Project)	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)
• Administrative Core (required)
• Biomedical Research Core (minimum of one is required)
• Research Projects (minimum of two are required)

NOTE: In addition to the Administrative Core, a viable Research Center would require a minimum of three highly meritorious components (i.e., two Research Projects and one Biomedical Research Core as a minimum).

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.

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.

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.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: State the overall goals of the Research Center and their significance to genitourinary health and disease. Summarize the general approach and expected outcomes and impact of the outcomes to achieving the goals of the Research Center and O Brien Cooperative Research Centers Program, as outlined in Section I. Funding Opportunity Description.

Research Strategy: Describe the major themes, goals, and objectives of the Research Center, including any background information. List the individual components (Research Projects and Cores, as well as the Education Enrichment and Opportunity Pool Programs) of the Research Center and explain their overall importance and contributions and how they will interact collaboratively to achieve the goals and objectives of the Center and the overall goals of the O'Brien Cooperative Research Centers Program as outlined in Section I. This should include a statement on how the Center as a whole is greater than the sum of its parts. The Center should also describe how the general strategy for how the Research Center will support the broader urology community. Funding Opportunity Description. Note the scientific and clinical disciplines represented in the Research Center components and respective, broad approaches for each Research Project (clinical, translational, and/or basic science). To foster true centers of excellence, it is anticipated all components will be within a single institution. Inclusion of multiple Institutions is permissible, if strongly justified.

Describe the overall scientific and administrative framework of the Research Center. Include an organizational chart. Note research and/or administrative leadership of Research Center personnel. Provide a leadership plan for oversight and operations of the overall Research Center, including conflict resolution for Center personnel. Provide a brief description and rationale for any proposed consortia or additional consultants. Investigators should fully explore their institutions to identify critical, interdisciplinary expertise to support the research and outreach goals of the Research Center.

Describe the function of any external advisory committees and proposed expertise to be represented, but do not list specific members. For renewal applications, please list members of the any external advisory committee and provide a summary of their activities in the previous project period.

Include information on the support and commitment of the parent institution for the Research Center, and the authority of the PD(s)/PI(s).

Letters of Support: Include all assurance letters from consortia investigators and institutions provided in support of 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 modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. In keeping with the goals of the NIDDK O'Brien Cooperative Centers Program, the applicants are expected to highlight potentially unique Core resources and how they plan to share them with other Research Centers and the research community, as well as provide an overview for and describe the oversight of the resource sharing activities of the Research Center as a whole.

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 NIH-defined human subjects research, clinical research, and/or 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 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 Research Center Director will serve as the Director of the Administrative Core and will oversee all scientific and administrative activities of the Center. Support for the Research Center s Director should be provided within the budget of the Administrative Core. The minimum level of effort for the Research Center Director (as Administrative Core Director) is 2.4 person months (20%). Administrative Core Associate Directors may be named as well, but the total, combined Administrative Core Directorship efforts may not exceed 4.0 person months. The Administrative Core may also include an administrative assistant(s), if justified.

The Administrative Core budget must include $100,000 direct costs per year to fund the Opportunity Pool Program and up to $75,000 direct costs per year to support the Educational Enrichment Program with a minimum of $25,000 of these direct costs specifically devoted to support for a summer student enrichment program. The Educational Enrichment Program may support the activities outlined in Section I, including travel support of investigators to learn new laboratory techniques, develop new collaborations, or engage in scientific information exchange. Additionally, the Administrative Core budget must include funds to support travel of the Research Center Director and senior/key personnel to attend up to 2 annual meetings relevant to the O Brien Centers Cooperative Research Program, as outlined in Section VI.

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.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the specific aims of the Administrative Core including the Educational Enrichment and Opportunity Pool Programs.

Research Strategy: The Administrative Core will serve as the primary managerial component for all activities of the Research Center. It will be responsible for the management of resources within the Research Center and outreach to the wider research community. The goals of this Administrative Core are to develop and maintain the vision and relevant goals of the Research Center; coordinate, manage, and integrate the Research Center’s components and activities, which includes coordinating ongoing research between the Research Projects and the Biomedical Core(s); harmonizing with the other O'Brien Cooperative Research Centers and collaborating with NIDDK Programs; and serving as a resource to the wider urologic research community.

Describe the organization and leadership plan of the Administrative Core, including the Educational Enrichment and the Opportunity Pool Programs, and their importance to the research theme of the Research Center. Describe the Administrative Core’s strategy for supporting the Research Center’s specific aims and goals and larger goals of the O'Brien Cooperative Research Centers Program and cooperation with O Brien Interactions Core and NIDDK program staff. Describe strategies for building and maintaining a functioning multi- and inter-disciplinary team (bringing scientists out of their research silos).

Describe the strategy by which the Administrative Core will effectively lead, organize, and provide (1) fiscal and resource management for the Research Center; (2) management of the Biomedical Core(s); (3) coordination for research efforts within the Research Centers and with the other urology programs, including the NIDDK KURe (K12) and NIDDK Developmental Center (P20) programs, and with the broader research community. Indicate who will be responsible for these activities. Describe the relationship and lines of authority and sanction by appropriate institutional officials.

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

Educational Enrichment Program

Describe the proposed activities of the Educational Enrichment Program. This Program may consist of seminar series, guest lectures, workshops, symposia, or other instructional opportunities that further the overall goals of the Research Center and broaden the reach of Center activities to the larger research community. Students, fellows, and junior faculty should be encouraged to take full advantage of all Educational Enrichment Program events. It is permissible for two or more Research Center Institutions to co-fund select activities of the Educational Enrichment Program. Travel support to attend meetings outside of the investigator's or attendee's discipline is encouraged.

Opportunity Pool Program

Opportunity Pool projects should represent new collaborations between Research Center's Project Leaders and (a) early stage investigators or (b) established investigators not previously involved in genitourinary research. The application should describe how these studies or projects would be solicited. Applications should not include details of the work proposed, but titles of potential studies or projects may be provided. Support for an Opportunity Pool Program study is limited to two years, with an option to extend it for an additional year pending review of progress.

For the Opportunity Pool Program, describe the internal institutional plans and procedures to ensure that all projects supported from this award will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in project proposals, appropriate ethical oversight and funded projects, and plans for data and safety monitoring for clinical trials, if applicable.

O'Brien Centers will identify appropriate Opportunity Pool candidates and solicit applications from within the Center's academic organization and from the larger research community. Opportunity Pool proposals will be assessed by independent content experts selected by the NIDDK. These individuals will provide comments on scientific merit for submitted Opportunity Pool applications to the NIDDK.

External Advisory Committee

Although optional, the use of an External Advisory Committee for each Center is highly advisable. The members must not be named in the grant application, though proposed areas of expertise may be noted. The process by which members are selected must be described in detail as part of the Research Strategy of the Administrative Core. This group, comprised of 3-5 members, may advise the Research Center Director and Center personnel in areas of scientific direction, budget, policy, collaboration, or other matters. For renewal applications, please list members of the External Advisory Committee that have served in the previous project period and provide a summary of their activities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The applicant can note that the Data Sharing Plan outlined in the Overall Component applies to the Project.

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.

When involving NIH-defined human subjects research, clinical research, and/or 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 Biomed Research 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 Biomedical Research 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.

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

A Biomedical Research Core Director should be named and is expected to contribute a minimum level of effort of 2.4 person months (20%). Personnel with less than 10% effort are considered Other Significant Contributors. Salary for participants with less than 10% should not be requested.

Budget Justifications: Describe the specific functions of all Biomedical 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.

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.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the major function, capability, and objectives of the Biomedical Core(s)

Research Strategy: A Biomedical Core(s) must function as a highly-innovative, shared resource that provides specialized and essential services, techniques, or instrumentation to Research Center participants. A Biomedical Core must also act as a resource for the larger O Brien Centers Cooperative Research Program and the urologic research community. To aid the Research Center in accomplishing it’s stated goals, it must be used by one or more Research Projects. While the Biomedical Core(s) is expected to serve one or more Research Projects, significant capacity to act as a national resource for the larger urology community should be described with sufficient allocation of resources.

Describe the purpose and objectives of the Biomedical Core(s) and its administration, organization, and operations. Include a description of services provided and their significance to accomplishing the scientific goals of the Research Center, as well as documentation of cost-effectiveness and plans for quality control. Describe how access to the Biomedical Core(s) by Research Center investigators and the larger urology research community will be prioritized, advertised, operationalized, and any fee structure. If a Biomedical Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant developments.

Provide a description of how the Biomedical Core(s) contributes to the goals of the Administrative Core, especially the Education Enrichment and Opportunity Pool Programs.

In addition, provide the following information:

• Brief description of Core scientific, technical, and support staff functions
• Description of current and/or projected services to Research Projects or other Cores
• Provide a summary of projected usage of Core services (e.g., assays performed, animals supplied, etc.) by Research Center Projects or other users, including PD/PI, name of grant, and funding source. Provide documentation that the Biomedical Core will used by at least two of the Research Projects.
• For renewal applications, provide a summary of Core usage over the previous project period, as described above.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The applicant can note that the Data Sharing Plan outlined in the Overall Component applies to the Project.

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.

When involving NIH-defined human subjects research, clinical research, and/or 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 Research Project.

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

SF424 (R&R) Cover (Research Project)

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 (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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) (Research Project)

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 (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead 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 Project Leader is required to have an established record of external funding and research accomplishment but is not required to have a background in genitourinary research. The Project Leader may serve as either the Research Center Director of an NIDDK O'Brien Urology Cooperative Research Center (U54) or a Urology Developmental Center (P20) but may not serve on both concurrently.

Budget (Research Project)

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

Minimum level of effort is 1.2 person months (10% effort) for the Project Leader. A Research Center Director may also serve as a Project Leader. Personnel with less than 10% effort are considered Other Significant Contributors, and salary support for such individuals should not be requested. Clinical personnel whose primary responsibility is participant recruitment or collection of information or samples for the purposes of phenotyping may request less than 10% effort if highly justified.

Budget Justifications: Describe the specific functions of all 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.

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.

PHS 398 Research Plan (Research Project)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the research focus with any required background information, the overall goals and hypotheses, relevance to genitourinary health and/or disease, and Specific Aims

of the project.

Research Strategy: Describe the research strategy of the Research Project in the same detail and format as expected for an investigator-initiated R01 grant application. In addition, include a

description of the relationship of the Research Project to the other Research Projects and how the Project addresses the overall goals of the Research Center and larger O Brien Cooperative

Research Centers Program. Describe how the Research Project will interact with the Research Center Cores and support the Education Enrichment and Opportunity Pool Programs.

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:

The applicant can note that the Data Sharing Plan outlined in the Overall Component applies to the Project.

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 (Research Project)

When involving NIH-defined human subjects research, clinical research, and/or 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.

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

Does the Research Center 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 Research Center 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? Is the whole of the Research Center greater than the sum of its parts? How will this Research Center support the broader urology community?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Research Center? 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? Is appropriate multi- or interdisciplinary expertise represented to achieve the goals of the Research Center?

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 Research Center? 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 Research Center 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?

Are the strategies for achieving the goals of the Research Center well-defined, feasible, and likely to lead to a multi-disciplinary effort within the Research Center, advance genitourinary research, and increase the research capability of the larger urology research community? Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, and appropriate ethical oversight of funded projects?

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?

Is there clear evidence of institutional commitment to the Research Center such as space, protected time, and/or additional financial support for co-funded activities such as the Educational Enrichment Program or the Opportunity Pool Program? Is there a suitable environment for Research Center 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.

The overall Research Center will also be evaluated as an integrated research effort focused on the genitourinary research mission of the NIDDK. The relationship and contributions of each proposed Research Project(s) and Biomedical 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 Research Projects and Cores as they relate to the central research goals?
• Will the Research Center structure enhance the value of the individual projects?
• If proposed, is there strong justification for a multi-institution Research Center?
• Are mechanisms proposed for regular communication among the Project Leaders and outside collaborators?
• Are the administrative structures in place for daily management of the Research Center, including internal evaluation of the Research Projects?
• How does this Research Center see itself integrating with other funded O'Brien Research Centers and P20s?
• For renewal submissions, is there evidence that the Research Center has successfully integrated activities with other funded O Brien Research Centers and has been a resource to the broader genitourinary research community?

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 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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period in all aspects of the intra- and inter-Research Center activities and successful support of the urologic research community.

Not Applicable

As applicable for the Research Center 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, a Core that by its nature is not innovative may be essential to advance a field.

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?

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?

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?

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? is 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? Is there a strong plan in place to allow for a successful Opportunity Pool Program and Educational Enrichment Program?

Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the research program it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed? Will the Core 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.

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

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

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

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

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

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 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).

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

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? Does the Biomedical Core(s) demonstrate innovation and high value contributions beyond conventional technical contributions typically found at a research institution?

is 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?

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

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?

Does the Biomedical Core serve at minimum one of the Research Center's Research Projects? Does the Biomedical Core have utility as a national resource to serve the larger urology research community?

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 Core proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

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

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

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

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

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

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 Research Project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Research Project proposed).

In addition, for applications proposing clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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

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

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the Research Project leader(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 Research 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?

In addition, for applications involving clinical trials:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research Project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility. How 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 Research Project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Do the proposed Research Projects collectively utilize at least two the following research approaches: 1) clinical or patient-oriented studies, 2) translational research using fundamental observations that inform clinical studies and management (or vice versa), and 3) basic science studies of underlying disease mechanisms?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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

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

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

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

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

If Resubmissions are not allowed for this FOA (i.e., are not included in Section II. Award Information Application Types Allowed), replace the text with Not Applicable . Otherwise, do not change.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

If Renewals are not allowed for this FOA (i.e., are not included in Section II. Award Information Application Types Allowed), replace the text with Not Applicable . Otherwise, do not change.

For Renewals, the committee will consider the progress made in the last funding period.

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.

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (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.
• Compliance with resource sharing policies

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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:

• Pursuing research objectives consistent with the research scope of the FOA and research favorably recommended by peer review;
• Conducting experiments and collecting the resulting data;
• Analyzing, interpreting and presenting results and plans to the Executive Steering Committee for approved activities;
• Submit interim progress reports, if requested, to the Executive Steering Committee for distribution to members of the Centers program and NIDDK staff. Such reports are in addition to the required annual noncompeting continuation progress report.
• Submit written responses to the recommendations of the External Expert Panel within two months of receiving those recommendations.
• Publishing results, conclusions, and interpretation of the studies.
• The awardees will agree to: 1) accept the coordinating role of the Executive Steering Committee which includes evaluating objectives and research goals of the Centers Program, and recommending modification, deletion or addition of projects within the Centers Program; 2) follow any common protocols in which they participate for multicenter projects that are approved by the Executive Steering Committee; and 3) accept the cooperative nature of the group process, including the establishment, where appropriate, of smaller collaborative groups comprised of interacting subprojects and/or cores.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• The NIDDK Project Scientist will participate in the overall coordination of the George M. O Brien Urology Cooperative Research Centers Program with the Executive Steering Committee. This includes efforts to improve and strengthen inter- and intra-center cooperation amongst the research projects of the Centers, and the Opportunity Pool Program, K12 KURe and the P20 Developmental Center Programs, particularly as it pertains to cross-fertilization of basic and clinical research activities within and between centers. As a means of improving inter-center cooperation, the Project Scientist will directly participate in the activities of the smaller collaborative groups as established by the Executive Steering Committee. This will include activity of the Opportunity Pool Program, the access to the Biomedical Research Cores and outreach to the K12 KURe, the P20 Developmental Centers, and the research community.
• The Project Scientist will also assist the research efforts of the Cooperative Research Centers Program by facilitating access to fiscal and intellectual resources provided by industry, private foundations, and NIH intramural scientists.
• The Project Scientist will, as required, help reprogram research efforts, including options to modify or terminate them, by mutual consent between the Cooperative Research Centers Program and NIDDK. In the event of disagreements among Program participants, the Project Scientist will assist in forming an arbitration panel as discussed below.
• Interact with each individual Center awardee evaluating objectives and research goals of that particular Center, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate this process and not direct it. The Project Scientist will also provide assistance in reviewing and commenting on all major transitional changes of an individual Center's activities prior to implementation to assure consistency with required goals of the George M. O Brien Urology Cooperative Research Centers Program.
• Retain the option to recommend the withholding of support from a Center research project or core materially failing to meet the technical performance requirements established by this Centers Program. This includes identifying jointly with participants of the Executive Steering Committee the need to add additional research projects or service cores to Centers or to phase out a Center project or core when performance standards have not been met; and
• Participate, where warranted, in data analyses, interpretations, and the dissemination of study findings to the research community and health care recipients including co-authorship of the publication or results of studies conducted by the Centers.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Additional responsibilities of the Program Official include:
• Interacting with the principal investigator(s) on a regular basis to monitor project progress. Monitoring may include: regular communications with the principal investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Executive Steering Committee, data safety and monitoring board, and related meetings.
• Monitoring project progress and may request that a project or portions of a project be closed for reasons including: (a) poor progress; (b) patient safety and regulatory concerns; (c) emergence of new information that diminishes the scientific importance of the project.
• Making recommendations for continued funding based on: a) overall project progress; b) cooperation in carrying out the research (e.g., attendance at Executive Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
• Appointing an independent External Expert Panel (EEP) that will annually review the overall Center Program progress and provide guidance to the NIDDK and the Executive Steering Committee.

Areas of Joint Responsibility include:

• Participating on an Executive Steering Committee consisting of the PDs/PIs from each of the participating centers and one NIDDK staff member who will be the Project Scientist. A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected jointly by the PD/PI and the NIDDK Project Scientist. Each full member of the Executive Steering Committee will have one vote. The purpose of the Executive Steering Committees will be to discuss and evaluate concerns and cooperative activities of the Cooperative Research Centers Program. The Executive Steering Committee will discuss and evaluate the activity of the Opportunity Pool Program, Biomedical Research Cores, and evaluate progress on research and pilot projects. The Executive Steering Committee will establish working subcommittees as necessary and provide feedback to subcommittee leaders at least bi-annually and implement changes in subcommittee membership or direction if needed. Awardee members of the Executive Steering Committee will be required to accept and implement policies approved by the Executive Steering Committee.
• Meetings of the Executive Steering Committee will be convened at least annually and at additional times if agreed upon by the Committee. The annual meeting will include the External Expert Panel. These meetings are separate from any regular conference calls. The purpose of these meetings is to share scientific information, assess scientific progress, identify new research opportunities and potential avenues of collaborations such as with industry, private foundations and/or NIH intramural scientists, establish priorities that will accelerate the translation of preclinical findings into clinical applications, and reallocate resources. The Executive Steering Committee will document progress in written reports to the NIDDK Program Official and will provide periodic supplementary reports upon request.
• In anticipation that some centers will have common research interests that address a specific basic and/or clinical research problem and thus, it is envisioned that subgroups will be formed to conduct coordinated research activities recommended by the Executive Steering Committee. As needed, the Executive Steering Committee will develop a publication policy regarding joint authorship of research reports derived from such collaborative efforts.

If there are no areas of joint responsibility, leave above text as is. Otherwise, for areas of joint responsibility (examples include membership, duties, voting, steering committee, etc.), revise above text as appropriate.

Dispute Resolution:

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

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Tamara G. Bavendam, MD, MS
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4733
Email: tamara.bavendam@nih.gov

Jason D. Hoffert, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-496-9010
Email: jason.hoffert@nih.gov

Ms. Diana Ly
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-9249
Email: diana.ly@nih.gov

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.