NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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

Over 28 million adults in the U.S. have diabetes mellitus (DM), and 86 million adults with prediabetes are at increased risk for developing type 2 diabetes mellitus (T2DM). There is considerable heterogeneity in the development and clinical presentation of DM in this broad patient population. Responses to pharmacologic therapy and the development of complications from diabetes can also vary among patients. Our lack of understanding of this heterogeneity limits the goal of precision medicine in diabetes care.

Diabetes has been traditionally classified as either type 1 or type 2 diabetes; however, other subtypes of diabetes like latent autoimmune diabetes in adults (LADA), congenital generalized lipodystrophy, Wolfram syndrome, neonatal/congenital diabetes, and maturity-onset diabetes in the young (MODY) have been characterized and are now recognized. An even greater range of unrecognized phenotypes for diabetes likely exists.

The identification and study of new cases of rare or atypical forms of diabetes may yield greater insight into the heterogeneity of more common forms of T2DM. Detailed phenotyping of these individuals and their families may help to characterize milder subtypes present in the spectrum of T2DM in the general population and reveal novel mechanistic pathways involved in the prevention and/or treatment of T2DM. Studying the underlying genetic background of these individuals may lead to the identification of function for the polymorphisms in or near known T2DM genes and explain the contribution of specific loci to aspects of polygenic T2DM. These genetic and phenotypic studies may help in identifying new biomarkers for screening and diagnosis. Furthermore, genetic studies may help to identify drug targets and catalyze the development of therapies for use, not only by these individuals with rare/atypical forms of diabetes, but also in subtypes of T2DM in the general population.

Dedicated efforts to discover and study rare/atypical forms of diabetes will not only aid individuals directly by informing their pathogenesis and treatment, but also address the heterogeneity of T2DM seen in the broader populations by providing new insights on mechanisms, diagnoses, and treatments for T2DM.

The Center should aim to become a national leader in efforts to discover and study individuals and families with rare/atypical forms of diabetes. While the mission of this Center is to identify rare/atypical forms of diabetes and promote collaborations to characterize molecular mechanisms underlying these rare disorders, it is intended that these studies will have important implications for understanding, preventing, and treating the general population with T2DM.

To accomplish these goals, the Center should:

(1) Develop a strategy and process for identifying individuals/families with rare/atypical forms of diabetes.

(2) Create a strategy for accomplishing research on individuals/families with rare/atypical forms of diabetes

(3) Build and manage a database and biospecimen repository to store data and samples from individuals with rare/atypical forms of diabetes for future analyses.

Overview

The Center should be a lead in a national effort to identify and study rare/atypical forms of diabetes. It can be an identifiable unit within a single institution such as a university medical center or a consortium of cooperating institutions. The Center must have an administrative plan to oversee all Center activities, manage resources, monitor progress, and ensure compliance with human subjects protections, and achieving proposed goals. The Center must establish and utilize a central IRB for all Center research projects. To achieve the objectives above, the Center must have (1) a Discovery and Analysis Project to identify and study individuals/families with rare/atypical forms of diabetes and (2) a Database and Biorepository Core to organize and store data and biospecimens for use in future research and data analyses.

Center Director(s) must have expertise and a track record of productivity and peer-reviewed research funding in diabetes, genetics, and/or rare diseases. The research environment must be able to support approaches for deep phenotyping and genetic analyses of rare/atypical forms of diabetes at the applicant institution and/or collaborating institutions. Applicants are also encouraged to form partnerships and leverage existing skills and resources with other NIH-funded centers in related areas (e.g. Diabetes Research Centers (https://diabetescenters.org/), Nutrition Obesity Research Centers (http://www.norccentral.org/home.do), Clinical and Translational Science Awards (https://ncats.nih.gov/ctsa/about/hubs), and the Undiagnosed Diseases Network (https://undiagnosed.hms.harvard.edu/about/)).

Administrative Core

The Administrative Core of the Center is responsible for managing resources, establishing a central IRB for research projects, and overseeing progress on all activities in the center. The Administrative Core must be able to initiate and utilize collaborations between investigators throughout the country, medical and professional societies, patient advocacy groups, and rare disease networks nationally and internationally. Additional outreach should be undertaken to raise awareness of research efforts, disseminate research progress, and foster translation and application of research findings to the broader community of individuals with T2DM. As part of this outreach effort, a Center website must be created and maintained.

Discovery and Analysis Project

The Center must have a Discovery and Analysis Component that is responsible for developing strategies and plans to identify, recruit and study individuals/families with new, rare/atypical forms of diabetes. The discovery of individuals/families with new, rare/atypical forms of diabetes can involve direct contact with individuals (e.g. patient contact registry), solicitations to care providers (e.g. outreach via professional societies), and/or institution-based mechanisms (e.g. network of diabetes clinics). There should be a unified plan for studying these individuals, and this plan should contain common elements of an individual’s history, demographics, physical exam, social history, family history, critical laboratory tests, and genomic data that will be captured in a systematic fashion on all individuals. The Discovery and Analysis Component should ensure compatibility and comparability of data collected for future larger-scale analyses.

While plans to solicit and support pilot and feasibility projects to foster novel analyses of newly identified individuals/families with rare/atypical diabetes are not appropriate in this application, funds for a pilot and feasibility program through the Center may be available at a later time.

Database and Biorepository Core

Rare diseases are generally considered conditions or disorders affecting less than 200,000 individuals in the U.S. The strategy for accomplishing more rigorous research on rare phenotypes requires efforts to accumulate data and biospecimens from groups of individuals with the same rare phenotype for further coordinated analyses. Therefore, the Center must create and manage a Data and Biospecimen Repository Core to store clinical and demographic information as well as biospecimens. This Data and Biospecimen Repository Core must manage the collection and centralized storage of data and biospecimens and have processes for sharing and tracking shared data and biospecimens.

Organization and Management of the Center

A Steering Committee will be formed to provide direction and coordinate activities for the Center. This group will establish procedures for the function of the Center. Once yearly, the Steering Committee and other key personnel are expected to convene at a meeting to review scientific progress, highlight key Center activities, and communicate with NIDDK staff. An External Evaluation Committee will also be formed by NIDDK to review the functioning and progress of the Center and to ensure that the Center is organized and operating optimally and efficiently.

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

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

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) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

Because the Center for the Identification and Study of Individuals with Atypical Diabetes Mellitus is likely to require a large and complex administrative structure, the Project Director/Principal Investigator (PD/PI) must have strong leadership abilities and demonstrated proficiency in managing large, multi-component programs.

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).

A button to access the online ASSIST system 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

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

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

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

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

The letter of intent, preferably electronically, should be sent to:

John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 7005
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817
Telephone: 301-594-7797
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall (Use for Overview)	12
Admin Core	12
Core (Use for Database and Biorepository Core)	12
Project (Use for Discovery and Analysis Program)	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:

• Overview: required
• Administrative Core: one required
• Database and Biorespository Core: one required
• Discovery and Analysis Program: one required

When preparing your application in ASSIST, 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.

Project Summary/Abstract: Describe the goals and objectives of the Center and how these contribute to accomplishing the overall goal to improve the understanding, prevention, and treatment of the broader, heterogeneous population with type 2 diabetes. Explain the overall strategy for achieving the goals of the Center. Provide an overview of the structure of the Center.

Project Narrative: Describe the relevance of the research fostered by the Center activities on public health in 1-3 sentences.

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.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Center Director and provide a valid eRA Commons ID in the Credential field.
• The Center Director must demonstrate leadership ability and skills to direct large multicenter projects. The Center Director should also have extensive clinical research experience. Expertise in diabetes, genetics and/or rare diseases is preferred; however, it is acceptable for the Center Director to lack this background if other members of the leadership team to provide knowledge in these content areas (see individual components).

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.

Personnel: The Center Director must devote a minimum of 2.4 person months to the Center through the individual components.

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

Specific Aims: State the short- and long-term goals of the Center and how these goals will be achieved. Describe how the expected outcomes will address the Center objectives listed in Section I. Funding Opportunity Description.

Research Strategy: Describe the major theme and structure of the Center, its goals and objectives, and provide background information to provide feasibility of accomplishing these goals. Explain the overall strategy for achieving the goals and objectives of the Center and the how different components of the Center will interact to achieve these goals. A timeline for Center activities and achievement of Center goals is strongly recommended.

Organization and Operation of the Center

Describe the organizational framework and include any relevant charts/diagrams. Be sure to explain the process for establishing relevant committees, cores, and programs within the Center and how they will function independently and jointly. Describe the selection process for roles on these committees/cores/components if key personnel have not already been identified. If external Advisor/Consultants are needed, describe their qualifications, but do not name them in the application. Plans to leverage skills and resources from other NIH funded centers in related areas (e.g. Diabetes Research Centers (https://diabetescenters.org/), Nutrition Obesity Research Centers (http://www.norccentral.org/home.do), Clinical and Translational Science Awards (https://ncats.nih.gov/ctsa/about/hubs), and the Undiagnosed Diseases Network (https://undiagnosed.hms.harvard.edu/about/)) must be outlined.

Letters of Support: Provide any letters of support, as appropriate. Include any letters of support for the proposed Center by appropriate institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the Center and its goals. The parent institution is expected to recognize the Center as a formal organizational component and provide documented evidence of space dedicated to the needs of the Center, protected time to devote to Center activities, staff recruitment, dedicated equipment, or other financial support for the proposed Center. The parent institution should provide assurance of its commitment to continuing support of the Center in the event of a change in directorship and a well-defined plan for this eventuality should be in place. Both the institution and pertinent departments must show a strong commitment to supporting the Center.

If collaborative linkages are being developed between the Center and other local NIH funded centers in related areas (eg. Diabetes Research Center or Clinical and Translational Science Award) a letter of agreement from the collaborating Center PD(s)/PI(s) should be included.

Do not provide letters of support from individuals who will not be involved in the Center's research 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, with the following modification:

Generally, Resource Sharing Plans are expected, but they are not applicable for this Component.

Appendix:

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

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

When preparing your application in ASSIST, 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 Administrative Core Director must demonstrate leadership ability and skills to direct large multicenter projects. The Administrative Core Director should also have extensive clinical research experience. Expertise in diabetes, genetics, or rare diseases is preferred; however, it is acceptable for other members of the leadership team to provide knowledge in these content areas if the Administrative Core Director lacks this background.
• An Acting Administrative Core Director must be identified to serve in the absence of the Administrative Core Director.

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

Personnel: The Administrative Core Director must devote a minimum of 2.4 person months to the Administrative Core. If the Center Director is also servicing as the Administrative Core Director, he/she must devote a minimum of 2.4 person months to the Center, and at least 1.2 of those months must be within the Administrative Core to ensure adequate oversight of the Center. If a multiple-PD/PI application, the combined effort of the PD(s)/PI(s) must be 2.4 person months.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Travel: Include travel costs for the Center Director, Core Directors, and pertinent Collaborators to attend an annual Center scientific meeting held every 12-18 months in the Bethesda area. Include travel costs for External Evaluation Committee Board members to travel to this annual meeting.

Supplies: Consumable supplies directly related to the operational aspects of the Administrative Core facilities are an allowable expense.

Consultants: Include costs associated with consultants (consultant fees, per diem, teleconferences, and travel) when their services are required by the Center.

Other Expenses: Funds for supporting the Center website may be requested.

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

Specific Aims: State how the Administrative Core will contribute to the goals of the Center and outline interactions of the Administrative Core with other Core/Program/Committees. Provide an overview of how the Administrative Core will set the overall direction of the Center and ensure optimal utilization of Center resources.

Research Strategy:

A clear plan should describe and address how and which members of the administrative team will oversee resources, coordinate interactions, and review progress of key Center Components and activities. This plan should outline policies and procedures that will be established for this purpose and when they will be modified. Strategies to mitigate and resolve disputes should be outlined.

A central IRB is a necessary aspect to the operation of research within this Center. The structure, functioning, and membership of this central IRB need to be clearly described, and policies and procedures for this entity outlined.

To build the research capacity for identifying and studying rare/atypical forms of diabetes, the Center must demonstrate their capability of and plans to forge collaborations with outside clinicians and investigators, healthcare systems and institutions, professional/medical societies, patient advocacy groups, and other rare disease efforts nationally and internationally. Details on the creation and maintenance of a website for the Center as part of these efforts must be provided. Furthermore, this Center must describe its outreach strategy to raise awareness on research efforts, disseminate research findings, and foster translation and application of research findings to the broader research and clinical community.

If external Advisor/Consultants are needed, describe their qualifications and function. Do NOT provide names or biosketches for Advisors/Consultants.

Letters of Support: Include any relevant letters of support, as needed. Do not provide letters of support from individuals who will not be involved in the Center's research 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, with the following modification:

Generally, Resource Sharing Plans are expected, but they are not applicable for this Component.

Appendix:

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

PHS Inclusion Enrollment Report (Administrative Core)

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

When preparing your application in ASSIST, use Component Type Project .

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

SF424 (R&R) Cover (Discovery and Analysis Program)

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 (Discovery and Analysis Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Discovery and Analysis Program)

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.

Facilities and Other Resources: Describe the existing environment, facilities, and resources available for use by the Discovery and Analysis Program. The Center is strongly encouraged to enter into cooperative agreements with cores already established within their institution, or with other Centers in close proximity, when the existing cores offer the services needed. These arrangements are important whenever greater efficiency or cost savings can be realized by such an agreement. Explain the process (including fee structure) to utilize the facilities and resources. Institutional resources capable of supporting the research endeavors must be made evident.

Project /Performance Site Location(s) (Discovery and Analysis Program)

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 (Discovery and Analysis Program)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Program 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 Program Director must be a clinical investigator with experience in the study of individuals or families with rare diseases. Expertise in diabetes and/or genetics is preferred; however, it is acceptable for other senior key personnel involved in this Project to provide knowledge in these content areas if the Program Director lacks this background.

Budget (Discovery and Analysis Program)

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

Personnel: The Program Director must dedicate at minimum 1.2 person months to this Project. Salary support for postdoctoral students is not permitted.

Equipment: A general listing of shared pieces of equipment to be used for activities in the Discovery and Analysis Program should be provided, and the process (including fee structure) for using the equipment should be described. If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase.

Travel: Travel costs for the Program Director to attend annual Center scientific meeting held every 12-18 months in the Bethesda area should be included in the Administrative Core budget and not in this section. If well-justified and related directly to Program activities/functions, limited travel funds for key professional staff may be requested to support travel to other sites for training or collaborative research. Funds for investigators and staff to attend national or international scientific meetings or workshops may not be requested.

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 (Discovery and Analysis Program)

Specific Aims: Describe the aims of this Program to support the goal of identifying and studying individuals/families with new/atypical forms of diabetes.

Research Strategy: The Discovery and Analysis Program is a critical aspect to the mission of the Center. There are two main parts of this Program that require detailed plans.

Discovery

Describe the overall strategy for identifying individuals with new rare/atypical forms of diabetes for further study. Outline the various modalities of outreach that will be implemented to discover these new/atypical forms of diabetes. Resources available for identifying and studying individuals should be described. Provide estimates of approximately how many individuals/families will be identified for future study using the planned methods of outreach. Provide examples of rare/atypical phenotypes that will be solicited. Describe the procedure that will be used to determine which individuals/families will be chosen for more in-depth study. Be sure to explain when and how individuals/families will be consented for further study, and when Center staff will interact with individuals/families with rare/atypical forms of diabetes.

Analysis

Describe the plan for studying individuals/families with rare/atypical forms of diabetes. Clearly delineate where and by whom the individuals/families will be studied. Explain when and how the Center will provide resources and services for studying these individuals. Include details on common elements of an individual's history, demographics, family history, social history, physical exam findings, critical laboratory test results and genomic data that will be collected in a systematic fashion on all individuals/families with rare/atypical diabetes. Describe plans to ensure compatibility and comparability of data to be collected for future larger-scale analyses. Explain how the current planned and future studies on these individuals will contribute to the overall goals of the Center.

Letters of Support: Include any letters of support for the Discovery and Analysis Program, as relevant. Do not provide letters of support from individuals who will not be involved in the Center's research 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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Consistent with achieving the goals of this Program, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data sharing plan.

The awardee is responsible for making all Program data collections and tools broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for this Program, for making data and materials available to the scientific community and the NIH for the conduct of research, as appropriate. The data sharing plan should include a sustainability strategy to ensure access to this data by the community once the Project period expires.

Applicants should discuss the following:

Availability of biological resources utilized and/or developed (cell lines, reporter systems, vectors, molecules, antibodies, biomarkers, etc.) as appropriate;

Availability of technologies and protocols developed with funds from this award as appropriate and consistent with achieving the goals of the Program.

Appendix:

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

PHS Inclusion Enrollment Report (Discovery and Analysis Program)

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

When preparing your application in ASSIST, use Component Type 'Core.

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

SF424 (R&R) Cover (Database and Biorepository Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Database and Biorepository Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Database and Biorepository Core)

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

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

Project Narrative: Do not complete.

Facilities and Other Resources: Describe the existing environment, facilities, and resources available for use by the Database and Biorepository Core. Explain the process (including fee structure) to utilize the facilities and resources. Institutional resources capable of supporting the research endeavors must be made evident.

Project /Performance Site Location(s) (Database and Biorepository Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Database and Biorepository Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of 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 Core Director must have leadership and organizational skills to guide in the collection, processing, analysis and distribution of human tissues and samples. The Core Director and his/her team must also have experience in developing and integrating databases from different experimental modalities. They must also have the skills to develop community data portals for providing open access summary data and accepting data use requests by the broader research community.

Budget (Database and Biorepository Core)

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

Personnel: The Core Director must dedicate at minimum 1.2 person months to this Project.

Equipment: A general listing of shared pieces of equipment to be used for Center activities should be provided, and the process (including fee structure) for using the equipment should be described. If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase.

Travel: Travel costs for the Core Director to attend annual Center scientific meeting held every 12-18 months in the Bethesda area should be included in the Administrative Core budget and not in this section. If well-justified and related directly to Program activities/functions, limited travel funds for key professional staff may be requested to support travel to other sites for training or collaborative research. Funds for investigators and staff to attend national or international scientific meetings or workshops may not be requested.

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 (Database and Biorepository Core)

Specific Aims: Describe the aims of this Core to support the goal of establishing and managing a database and biorepository of individuals/families with new/atypical forms of diabetes and facilitating the use of data and specimens for future study.

Research Strategy: The Database and Biorepository Core is another key aspect to accomplishing the mission of the Center. There are two main sections of this Core that require detailed plans.

Database

Describe the means for submitting and integrating data into a searchable data structure in a timely manner. Provide details on what data will be collected and stored. Explain how data will be curated and harmonized, instances where this is necessary, and how it will provide enhanced querying and analyses of data across individuals/families/phenotypes/disorders. Describe how a unique identifier for each subject will be assigned and utilized. Explain proposed methods and processes that will be set up to provide easy links to data from the same subject in multiple databases. Outline opportunities to link data from this database with related data that may be stored on other public databases (e.g. dbGaP, federated iPSC registries). Describe plans for providing a public, searchable catalog of open access data to encourage and facilitate use of data in the database for further analyses. Provide a detailed plan (including a timeline) for allowing, sharing, and tracking use of identifiable data. Plans to assure the security, privacy, and confidentiality of data in this database must be provided.

Biorepository

Provide plans and procedures for acquisition, shipping and receipt of biospecimens (e.g. blood, saliva, DNA, plasma, derived cell lines), and address how sample viability and integrity will be ensured. Outline specific biospecimen types and quantities that are planned as standard collections. Describe any flexibility for accepting additional biospecimens beyond what is planned. Describe procedures for processing and creating distributable biospecimen derivatives for future study. Provide plans and procedures for sample storage and distribution including biospecimen tracking and safeguards against accidental loss of biospecimens. Explain how variation in biospecimen collection, processing, and storage will be minimized. Describe plans to encourage and facilitate use of biospecimens for additional research and procedures for allowing, sharing, and tracking use of biospecimens.

Although NIDDK has a repository, it will not serve as the repository for the Center during the project period. Outline plans to continue the Center Database and Biorepository and to make data and specimens available to the broader research community after Center funding ends. If continuation of the Database and Biorepository is not feasible without Center funding, state plans to relinquish data and specimens to NIDDK.

Letters of Support: Include any letters of support for the Database and Biorepository Core, as relevant. Do not provide letters of support from individuals who will not be involved in the Center's research 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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Consistent with achieving the goals of this program, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data sharing plan.

The awardee is responsible for making all Project data collections and tools broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for this Project, for making data and materials available to the scientific community and the NIH for the conduct of research, as appropriate. The data sharing plan should include a sustainability strategy to ensure access to this data by the community once the Project period expires.

Applicants should discuss the following:

Availability of biological resources utilized and/or developed (cell lines, reporter systems, vectors, molecules, antibodies, biomarkers, etc.) as appropriate;

Availability of technologies and protocols developed with funds from this award as appropriate and consistent with achieving the goals of the program.

Appendix:

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

PHS Inclusion Enrollment Report (Database and Biorepository Core)

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) 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.

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

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

Does the Center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the 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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the 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?

Specific to this FOA: What are the scientific and administrative leadership abilities of the proposed Center leadership? Do they demonstrate commitment and ability to devote adequate time to the effective management of the Center? Is the Director well-qualified and appropriate?

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 Center? 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 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 children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Will the organization of the Center and procedures for establishing and coordinating activities between relevant Cores and Programs be sufficient for carrying out the goals of the Center? Are resources from other NIH funded centers being utilized in a meaningful way, and is the plan to utilize outside resources sound? Is the timeline for achieving the Center goals feasible and realistic?

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?

Review Criteria - Administrative Core

Reviewers will consider each of the criteria below in their overall impact score for the Administrative Core. Reviewers should NOT provide individual criterion scores for the Administrative Core.

Is the administrative and organizational structure appropriate and adequate to the attainment of the Center goals? Are the experience, level of commitment and leadership ability of the Administrative Core Director and staff adequate to manage the Center? Are plans for coordination, establishment of a strong collaborative environment, and identifying and resolving problems appropriate? Is the management plan for overseeing resources and reviewing progress of key Center Core/Program/Committees Programs appropriate? Will the plans for the composition and functioning of a central IRB for research conducted in the Center be feasible and suitable? Are there a strong plan and ability to create meaningful internal and external collaborations to move the Center research efforts forward?

Review Criteria - Discovery and Analysis Program

Reviewers will consider each of the criteria below in their overall impact score for the Discovery and Analysis Program. Reviewers should NOT provide individual criterion scores for the Discovery and Analysis Program.

Are there sufficient expertise, commitment, and leadership ability in the Director and team for the proposed activities of the Discovery and Analysis Program? What is the likelihood that the plans for outreach and identifying rare/atypical forms of diabetes will yield sufficient numbers of individuals/families for research? Will the plans to determine which individuals/families will be chosen for further in-depth study capture the relevant study population and include all important individuals for study? Is the plan to study individuals/families with rare/atypical forms of diabetes feasible, and are the resources and services sufficient for studying these individuals? Will the proposed collection of common demographic, phenotypic, and genetic information provide meaningful research findings? Is the plan to ensure compatibility and comparability of data collected for future research sound? Will the planned activities of the Discovery and Analysis Program contribute significantly to the goals of the Center?

Review Criteria - Database and Biorepository Core

Reviewers will consider each of the criteria below in their overall impact score for the Database and Biorepository Core. Reviewers should NOT provide individual criterion scores for the Database and Biorepository Core.

Are there sufficient expertise, commitment, and leadership ability in the Director and team for establishing and managing the database and biorepository? Is the quality of the relevant facilities and resources provided sufficient to support the formation and functioning of the database and biorepository? Is the plan to submit, harmonize, and integrate data into a searchable data structure feasible and will it yield organized and meaningful data for future research efforts? Are the plans to assign a unique identifier and utilize it for future plans to merge data/samples sufficient? Will the searchable catalog of open access data encourage and facilitate the use of data within the database by internal and external investigators? Will the plan to acquire and process biospecimens yield adequate sample viability and integrity for future research? Is there adequate quality control management? Is the plan to share and track use of data and biospecimens robust? Are the processes and criteria for prioritization and usage of data and samples appropriate?

As applicable for the Center 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

When the proposed 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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

Not applicable

Not applicable

Not applicable

As applicable for the 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.

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

As part of the scientific peer review, all applications:

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

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Adequacy of resource sharing plan, as appropriate.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

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

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 75s 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

• Awardee(s) will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• The Program Director/Principal Investigator (PD/PI) will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement (FOA) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• Awardee(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.
• Awardee(s) is/are responsible for their staff in maintaining confidentiality of the information as developed by the Center, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the Steering Committee (SC) as well as any confidential information received by third party collaborators.
• Awardee(s) is/are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis and (2) for clinical studies, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense.
• Awardee(s) must share data, materials, models, methods, information and unique research resources that are generated by the projects in concordance with the Center policies in order to facilitate progress. When appropriate, and in accordance with NIH policies, as well as NIDDK policies, awardees will be expected to collaborate; share novel reagents, biomaterials, methods and models and resources; and share both positive and negative results that would help guide the research activities Center collaborators.
• Awardee(s) must analyze, publish and/or publicly release and disseminate results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and achieving the goals of the FOA.
• Awardee(s) will be required to participate in a cooperative and interactive manner with members of the Center including designated NIH staff (e.g., Program Official, Project Scientist).
• Awardee(s) agrees to work with the Steering Committee and designated NIH staff to establish agreements that address the following issues: (1) procedures for data sharing among collaborators and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the Center as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing bio-specimens under an overarching MTA amongst Center collaborators that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• Awardee(s) agree that each industry collaboration should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures.
• The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this grant are applicable clinical trials subject to FDAAA, the sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors (http://icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html).
• Awardee(s) must agree to comply with the processes and goals as delineated within the FOA.
• The awardee(s) is/are responsible for making all study materials and procedures broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research. The data sharing plan should include a plan to accomplish this.
• The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. Upon completion or termination of the Center, if the awardee will not continue the Database and Biorepository Core services, the PI or his/her designee will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution if requested by NIDDK. In addition, if applicable, the PI or his/her designee will work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study’s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Subsequently samples and data will be available to the wider scientific community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/ and,
• http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals/ , and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm/ ), as well as the NIDDK policy for data sharing in multi-center and large single-center clinical studies http://www.niddk.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf/.

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

The NIDDK will designate program staff, including a Program Official and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award.

The NIDDK will invite External Consultants with relevant scientific expertise. The External Consultants will meet to review the progress of the research projects and to advise NIH staff of scientific developments and opportunities that may enhance the achievement of the study goals.

An NIH IC Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows:

• The NIH Project Scientist will coordinate and facilitate the research projects, attend and participate in all meetings of the Center Steering Committee, and act as (a) liaisons between the Awardee (Steering Committee) and the External Consultants.
• The NIH Project Scientist will be a member of the Steering Committee and, as determined by that committee, and its Subcommittees as needed. Only one NIH Project Scientist will vote on the Steering Committee. Other designated NIH program staff attending the steering committee meetings will be an ex officio (non-voting) member(s).
• Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.
• The NIH Project Scientist, and other designated NIH program staff will help the Steering Committee develop and draft operating policies.
• The NIH Project Scientist and Program Official will review the scientific progress, cooperation in carrying out research, and maintenance of high quality research in each of the individual research project(s), and review the project(s) for compliance with operating policies developed by the Center Steering Committee, and may recommend to the NIH to continue funding; withhold support or restrict an award for lack of scientific progress or failure to adhere to policies established by the Center Steering Committee. Review of progress may include regular communications with the PD/PI and NIH staff, periodic site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of periodic external review of progress.
• The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (a) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or Center policy and procedure, (b) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or any human subjects ethical issues that may dictate a premature termination.
• The NIH will name additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist and the Steering Committee in carrying out the goals and aims of the approved studies. The NIH will have one vote for any key committees, regardless of the number of NIH personnel involved.
• The Project Scientist will have substantial scientific programmatic involvement in quality control, preparation of publications, research coordination and performance monitoring. The Project Scientist will have the same access and privileges to any data generated by the grantee. The dominant role and primary responsibility for these activities resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIDDK Project Scientist.
• The NIH Project Scientist serve as a resource with respect to other ongoing NIH activities that may be relevant to the Center to facilitate compatibility and avoid unnecessary duplication of effort.
• The NIH Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of (a) common research protocol(s) and statistical evaluations of data and in the publication of results.
• The NIH Project Scientist may review procedures for assessing data quality and monitor study performance.
• The NIH Project Scientist may be (a) co-author(s) on study publications. In general, to warrant co-authorship, the NIH staff must have contributed to one or more of the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

The NIDDK Program Official identified in the Notice of Award will:

• Interact with the Program Director(s)/Principal Investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the Program Director/Principal Investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.
• Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.
• The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.
• Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
• Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Areas of Joint Responsibility include:

Through the Awardee, (Steering Committee) and NIH staff, the study members will cooperatively develop and implement processes for Center activities, determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the Center, consistent with NIH policies and achieving the goals of the program as described in the FOA. The following bullets relate to areas of joint responsibility:

• Steering Committee (SC)
• An SC Chairperson will be chosen by the NIH. In collaboration with the SC members and the NIH Project Scientists, the Chairperson is responsible for coordinating the SC activities, for preparing meeting agendas and for chairing meetings.
• The Steering Committee (SC) is composed of the SC Chairperson, the NIH Project Scientist, the Center Director (one of the PIs must be selected to represent the group on the SC, in the case of a MPI application), the Database and Biorepository Core Director, and the Discovery and Analysis Project Director, to serve as the main governing board of the Center. Each full SC member will have one vote. All major scientific and policy decisions will be determined by (voting policies as established by the SC at the initial meeting). This committee will operate to develop collaborative protocols, identify impediments to success and strategies to overcome them, develop shared tools for disseminating information about the projects, and identify opportunities for sharing techniques, materials, information and tools developed within each individual project. The SC activities and decisions will consider the advice of the External Consultants.
• The SC will have meetings that will be organized by the SC Chairperson. Any SC member may place items on the agenda. These should be communicated in advance of the meeting to the Project Scientist(s) who will distribute these to all members. The designated NIDDK Program Official of the Center may be asked to participate in order to provide additional information and to summarize actions that are taken.
• The SC may, as it deems necessary, invite additional, non-voting scientific consultants to meetings at which research priorities and opportunities are discussed. The NIH reserves the right to augment the expertise of the Steering Committee when necessary.
• The SC will be responsible for organizing the yearly Scientific Retreat.
• There will be (an initial) in-person meeting and one in-person Steering Committee meeting annually. These meetings will incorporate participation and recommendations of the External Consultants (External Experts) when determined by NIH staff (or as stipulated in the FOA).
• NIDDK staff, in concert with the SC, will have the option to redirect research activities within the Center if it is considered beneficial to the overall
• The NIH Project Scientist may work with Center collaborators on issues coming before the Steering Committee and, as appropriate, other committees.

External Consultants

• An independent panel of External Consultants will be established by the NIDDK. The External Experts will review periodically interim progress of the Center and report to NIDDK staff.

Dispute Resolution:

Manual Chapter Instructions: Using standard template language if possible, describe pertinent dispute resolution mechanisms applicable to scientific disagreements between awardees and the IC, related to programmatic decisions on scientific/technical matters.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

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

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

Christine G. Lee, M.D., M.S.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8806
Email: [email protected]

Carol R. Haft, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7689
Email: [email protected]

Dianne Camp, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7682
Email: [email protected]

Christina Coriz
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8848
Email: [email protected]

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

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