Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Much remains to be learned about the causes and triggers of T1D in humans. Documenting the series of events that leads to beta cell dysfunction and loss, particularly during the early stages of life and the asymptomatic phase of human T1D, would provide critical insights into the origin of the disease. A molecular exploration of human pancreata could also help identify biomarkers highly specific for T1D, develop means of controlling the regenerative capacity of the pancreatic compartment in individuals with T1D, and design therapeutic strategies to delay or stop the progression towards full-blown T1D by slowing or preventing the development of beta cell-specific autoimmunity.

While it is now possible to identify individuals at highest risk for developing T1D prior to disease onset, T1D remains a particularly difficult disorder to investigate given our inability to access the target organ in living individuals. Current limitations include:

• Our inability to safely biopsy the human pancreas during the lifetime of individuals at risk of developing the disease prevents the molecular staging of the disease process;
• Most studies using human pancreata or human islets are not consistently linked to the in-depth clinical histories of the donors;
• Most studies using human pancreata as starting material examine either pancreatic sections or isolated islets, but rarely both. Therefore, human tissues are not subjected to a coincident and multi-dimensional phenotyping (molecular, cellular and functional) that would maximize the information being collected on a given specimen;
• Most of the protocols used for collecting and fixing pancreatic specimens from cadaveric donors are not compatible with state-of-the-art molecular techniques that can report on detailed phenotypic traits at the molecular level and with single-cell resolution;
• Most of the research on human pancreatic tissues or isolated islets consists of independent investigations performed by individual research groups and do not result in the co-registration of multimodal measurements collected by a variety of investigators using complementary technologies on shared specimens.

A deeper understanding of the origins and diversity of human T1D would be greatly facilitated by access to a collection of extensively phenotyped human tissues that could be shared with the research community to develop integrated (molecular, anatomical and functional) signatures of the developing, healthy, pre-T1D and T1D human pancreas. In addition, a parallel exploration of pancreatic specimens collected from individuals with islet dysfunctions unrelated to T1D (such as T2D, Wolfram syndrome, Fanconi anemia, congenital hyperinsulinism, pancreatic steatosis), or from individuals with conditions characterized by changes in beta cell mass (pediatric obesity, recent gastric bypass surgery, pregnancy) would facilitate the discovery of molecular signatures that are highly specific for beta cell dysfunction in T1D and the exploration of the regenerative capacity of pancreatic islets in individuals with T1D.

The goal of this initiative is to create a Human Pancreas Procurement and Analysis Program (HPPAP) that will be tasked to develop and implement strategies for:

• The collection and extensive characterization of pancreata recovered from individuals with pre-T1D (i.e. positive for multiple islet autoantibodies), recently diagnosed T1D or established T1D, as well as from individuals with various islet dysfunctions or physiological conditions characterized by changes in beta cell mass, and from very young organ donors;
• The sharing of the residual tissues and the linked datasets resulting from the functional and molecular phenotyping of the HPPAP tissues with the broader research community for expended analysis as appropriate;
• The organization of all omics and image-based datasets derived from the study of HPPAP tissues into an open-access reference resource for the diabetes research community (PANC DB).

Specifically, the HPPAP team will be responsible for the following functions:

1) Assemble and phenotype a diverse collection of human pancreata:

HPPAP should propose and implement a strategy for identifying and collecting human pancreatic specimens and their associated clinical records from donors with pre-T1D, recently-diagnosed T1D, overt T1D or physiological conditions affecting pancreatic function or beta cell mass, as well as from healthy donors from a variety of age groups. HPPAP should establish criteria for inclusion/exclusion of tissues into the HPPAP collection with the goal of generating datasets that reveal unique aspects of pancreatic function/dysfunction associated with the development of T1D or of the capacity of the human endocrine pancreas to regenerate a functional beta cell mass.

At a practical level, HPPAP activities could include:

• Identify, coordinate and manage tissue source sites through subcontracts to acquire human pancreata from cadaver donors. The tissue source sites would be responsible for skilled and expedited autopsy, sample acquisition and processing, preservation, as well as collecting and completion of proper documents, including consents. Ideally, HPPAP would partner with clinical centers and/or individual surgeons with documented expertise in processing human pancreatic tissues and pancreatic islets for research purposes. HPPAP should ensure that the human sample collection and handling procedures comply with current NIH policies;
• Collect whenever possible the de-identified medical records of the donors to include diabetes or pre-diabetes history (elevated blood glucose or hemoglobin A1C), but also information about co-morbidities such as vascular disease, renal insufficiency, medications and overall health. The applicant should propose a strategy to identify and characterize donors with pre-T1D or recent T1D using measurements such as islet cell autoantibodies. HLA typing on antibody-positive individuals would be an important piece of information to collect. Ideally, fibroblasts from the donors would be collected to enable future derivation of iPSC lines;
• Collect the pancreata using tissue-processing protocols that allow for multiple analytical paradigms to be used on the same specimen, including functional studies on subsets of live islets and a variety of molecular studies on fixed tissue. This could be achieved by the systematic isolation of live islets from part of the tissue (for example for measuring glucose-induced insulin secretion, analyzing transcriptomics on sorted cell populations or studying long-term function of islets transplanted in humanized mouse models) and fixation of the rest of the specimen using a variety of procedures, including tissue-clearing techniques such as CLARITY, to allow for multiplexed analyses using antibody-based technologies (such as immunocytochemistry or mass cytometry) and multi-omics technologies with single-cell resolution (such as MALDI or SeqFISH);
• Define and run a standard set of deep phenotyping experiments (molecular, functional and anatomical) to create a reference dataset that would be associated with each and every HPPAP specimen and would be shared with the future users of these specimens as appropriate;
• Catalog, annotate and store all phenotyped HPPAP pancreata using methods that preserve bio-specimen integrity;
• Maintain an information system for sample management that facilitates sharing of the tissue and the linked experimental data with the user community, but also the addition of complementary datasets as generated by the users of the HPPAP specimens, as appropriate.

2) Share the phenotyped specimens and related data with a community of users:

HPPAP will be responsible for sharing with the research community all residual human pancreatic tissues following the completion of a standard set of functional and molecular assays by the HPPAP team. HPPAP will also share with the scientific community all the clinical, functional and phenotypic data as collected by the HPPAP team on all specimens. HPPAP will encourage investigators with unique skill sets, technologies or scientific interests to enrich and expand on the standard set of analyses that will be systematically performed by the HPPAP team. HPPAP will also actively promote the sharing of all additional data acquired by users of HPPAP specimens by:

• Requiring that all results derived from the exploration of HPPAP tissues be deposited in the HPPAP database in a timely manner as appropriate;
• Organizing working groups to help with the development of standardized formats for the generation and capture of data and to suggest improvements to the existing database structure and computational tools;
• Organizing regular meetings ofusers of HPPAP tissue specimens, either virtual or in person, to discuss findings;

3) Develop an open-access reference resource (PANC DB):

HPPAP will be responsible for organizing and integrating all functional, anatomical and molecular data and metadata generated by the HPPAP team and the HPPAP tissue user community into a comprehensive and searchable database (PANC DB) that will serve as an extensive source of information about the developing, healthy and diseased human pancreas. The successful development of PANC DB will require the recruitment of a stellar computational group with demonstrated expertise in building and applying state-of-the-art analytical tools for the integration and visualization of datasets generated using different experimental modalities such as image-generating and multiple omics technologies. Whenever possible, the HPAPP computational analysis team should leverage strategies and tools that are being developed or used for the multimodal phenotyping of other complex tissues rather than reinventing tools and approaches specific to the pancreatic tissue. Ideally, the information accessible through PANC DB will represent an extensive cellular and molecular analysis of all cell types present in the human pancreas to include exocrine and endocrine cell subtypes, intra- and inter-islet vascular and neuronal networks, pancreatic ducts and immune cells. As a resource, PANC DB should enable the scientific community to explore important aspects of pancreatic function and dysfunction, and should facilitate scientific endeavors such as exploring 3D structural and functional relationships at the cellular and organ-wide level, generating mechanistic hypotheses related to T1D pathogenesis or the regenerative capacity of the human endocrine pancreas, or identifying cell-specific biomarkers and candidate drug targets. In order to achieve these goals, the HPPAP computational biology team may want to consider undertaking most if not all of the following functions:

• Develop tools and protocols to extract, curate and incorporate all data resulting from the study of HPPAP tissues into a comprehensive database;
• Establish an application framework to facilitate complex data loading including detailed experimental descriptions. The database should be flexible and extensible to manage and integrate multiple types of data, including genomics, proteomics and metabolomics data, but also complex image-based datasets;
• Develop/adapt analysis tools for data integration, including for the co-registration of data of disparate but complementary nature (anatomical, functional and multiple omics);
• Develop, maintain and enhance an open-access portal with user friendly interfaces to allow the research community easy access to the data;
• Develop/adapt and share tools for on-line data mining, image analysis and visualization of data and metadata by the research community;
• Incorporate existing data from relevant databases and/or link to existing resources;
• Work closely with the user community to build or make available any additional tool or feature that can facilitate the deposition, archiving, extraction, analysis or visualization of data;
• Assist HPPAP investigators in deposition of datasets to PANC DB;
• Ensure data security with backup strategy;
• Ensure that datasets and documentation are in a widely-adopted standard format for continuing data accessibility beyond the close out of the project.

4) Forge partnerships with existing programs:

HPPAP will be responsible for leveraging the activities of relevant programs through the formation of strategic partnerships with existing efforts related to its mission. Such partners should include at least the following:

• The NIDDK-supported Integrated Islet Distribution Program (IIDP, https://iidp.coh.org/), which focuses on the distribution of high-quality dissociated human islets to the research community. HPPAP should seek to leverage the strength of the IIDP procurement network to assist in identifying potential donors for entry into the HPPAP analysis pipeline, and collaborate with IIDP to fine tune and harmonize best practices for procurement and isolation of human islets and pancreatic tissues for research;
• The JDRF-supported Network for Pancreatic Donors with Diabetes (nPOD, http://www.jdrfnpod.org/), which facilitates the broad distribution of a large number of fixed tissue samples recovered from human pancreas donors, with a particular focus on donors with T1D or with a family history of T1D. While nPOD has put significant effort into sharing experimental results obtained by its user community, the nPOD fixation protocols and the absence of functional analyses of live tissues prior to fixation currently limit the types of information that can be gleaned from the extensive nPOD collection. Wherever possible, the HPPAP should leverage the extensive nPOD resources to advance HPPAP objectives. For example, the HPPAP team may consider forming a strategic alliance with nPOD to facilitate any sample archiving or distribution that may be needed, and/or seek to harmonize data acquisition and display with nPOD to allow for the seamless integration of datasets between the two programs.
• The Human Islet Research Network (HIRN, http://hirnetwork.org/about-us/overview): Upon funding, the HPPAP team will integrate with the NIDDK-supported HIRN, whose overall mission is to better understand how human beta cells are lost in T1D, and to find innovative strategies to protect or replace functional beta cell mass in diabetic patients. HPPAP is expected to work closely with the HIRN Coordinating Center (HIRN-CC) and Bioinformatics Center (HIRN-BC) to facilitate the organization and sharing of data and reagents generated by HPPAP activities. At a minimum, data and analytical tools made available through PANC DB should become easily accessible through the HIRN portal. In addition, many HIRN investigators are already studying human pancreata using multi-omics approaches, and should be actively encouraged to become HPPAP users and contributors of data to PANC DB. An effort should be made to integrate all relevant data generated by HIRN investigators into PANC DB. In conjunction with the HIRN-CC and the HIRN-BC, the HPPAP should develop workshops and community outreach strategies to optimize community use of HPPAP resources, to gather feedback from users, and to implement new community-sourced use cases. The HPPAP team will be expected to work collaboratively with all of their HIRN colleagues and to contribute to an environment of sharing and trust across the network. All HHPAP participants will be expected to adhere to the sharing policies developed by the HIRN as a term of the award and to the Cooperative Agreement Terms and Conditions of Award. The NIDDK staff will designate a member of the HPPAP team to represent HPPAP on the HIRN Trans-network Committee (HIRN-TNC) who will be expected to participate to all meetings of the HIRN-TNC. HPPAP Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also participate in the annual HIRN Investigator Scientific Retreat. In the application, budget requests must include costs for the PD(s)/PI(s) and up to three other HPPAP staff members to attend the annual HIRN Investigator's Scientific Retreat.

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• 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.

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

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

Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: 301-594-8897
Email: calvof@mail.nih.gov

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

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

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

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

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

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

As a group, the assembled team of investigators will need to combine skills and expertise in all of the areas that are required to build and operate an efficient HPPAP program, including:

• Strong knowledge of human pancreas physiology and/or pathophysiology;
• Experience with collection, analysis and distribution of human tissues;
• Development or use of state-of-the-art analytical tools for the integration of datasets generated using different experimental modalities (such as multi-omics measurements) in complex tissues;
• Development of community data portals for the visualization and sharing of multimodal datasets with the scientific community;
• Demonstrated experience working productively in collaborative environments

Relevant individual background, expertise and proven contribution to the required fields should be clearly documented in the application, as the appropriateness of the combined team expertise to the mission of HPPAP will be part of the review criteria.

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should also provide within their budgets an estimate of the tissue procurement costs. This should include the price of obtaining the human tissue specimens, as well as an estimate of the number of specimens to be collected each year and throughout the duration of the grant.

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

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

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

Research Strategy: The HPPAP application should propose an estimated number of human pancreatic specimens to be collected and characterized per year of operation; a strategy to coordinate the tissue source sites for sample acquisition; and a plan to accommodate and implement different protocols for state-of-the-art molecular biology analyses as described above.

In order to facilitate the sharing of the limited amount of residual HPPAP tissues with non-HPPAP investigators, applicants should propose a mechanism by which requests for access to HPPAP tissues by outside investigators will be granted based on the recommendation of a separately empaneled group of independent experts, and following the review by this group of experts of a short research proposal describing the need for the use of these HPPAP tissues.

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.

Upon completion or termination of the HPPAP project, the awardee is responsible for making all HPPAP 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 each 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 HPPAP data by the community once the project period expires.

• Applicants should discuss the following:
  • Availability of biological resources utilized and/or developed (mouse models, 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.
• Letters of Support: HPPAP applications should identify the tissue source sites and provide supporting letters from these sites to demonstrate capacity and commitment to deliver the types and numbers of human pancreatic specimens described in the grant application.

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

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

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

Since these awards will be issued with a 5-year budget and project period from the same fiscal year, the grantee will not have any authority for an automatic extension nor will one be permitted with NIH prior approval. Funds will not be available for expenditure beyond September 30th of the 5th fiscal year after the period of availability. Thus, extensions of the budget/project period will not be allowed.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIDDK, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDDK Review Branch Office by email at calvof@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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

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

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

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

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Is the expertise in the areas of human pancreas physiology/pathophysiology and of collection, analysis and distribution of human tissues well represented in the proposed team of investigators? Does the computational team have documented experience developing and applying state-of-the-art analytical tools for the integration of datasets generated using different experimental modalities in complex tissues? Does the bioinformatics team have documented experience with the building of a community data portal and sharing complex multimodal datasets? Do PD(s)/PI(s) provide evidence of experience working productively in collaborative environments?

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 project? 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? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

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

Collaborative Research Opportunities

Does the project present an opportunity for research that would be enhanced by consortium interaction, collaboration and expertise?

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 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 U01, 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:

• The HPPAP Awardee will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies and tool-development efforts conducted under the terms and conditions of the cooperative agreement award.
• The HPPAP Awardee 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 in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• The HPPAP Awardee 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 HHS, PHS, and NIH policies.
• All staff of the HPPAP Awardee will maintain the confidentiality of the information received or generated in the context of HPPAP activities, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators.
• The HPPAP Awardee must analyze, publish and/or publicly release and disseminate results, data, tools and other products of HPPAP activities 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 goals of the FOA.
• All staff of the Awardee will be required to participate in a cooperative and interactive manner with NIH staff, one another, the HIRN CC and HIRN investigators in all aspects of HPPAP activities.
• The HPPAP Awardee is expected to share data, materials, tools, methods, information and unique research resources that are generated by the project in accordance with HIRN-AH policies in order to facilitate progress as appropriate and consistent with achieving the goals of the program.
• The HPPAP Awardee will submit a list of milestones and project deliverables to the to the HPPAP Program Officer and the HPPAP Project Scientist prior to the first HIRN meeting that follows issuance of award, and will update this list annually prior to the HIRN Investigator Scientific Meeting.
• The HPPAP Awardee agrees to work with the HIRN-AH Steering Committee, the HIRN consortia Steering Committees and the HIRN Trans-Network Committee to establish agreements that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium 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 biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• The HPPAP Awardee agrees that industry collaborations 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 and any policies and procedures developed by the HIRN-AH.
• The HPPAP Awardee must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.

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 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 NIH will invite experts with relevant scientific expertise to provide feedback to the NIH on HPPAP activities. The External Experts will meet to review the progress of the HPPAP project and to advise NIH staff of opportunities that may enhance the operation and achievements of the HPPAP.
• An NIDDK Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIDDK Program Official as follows:
  • The NIH Project Scientist will coordinate and facilitate the activities of the HPPAP, attend and participate in all meetings of the HPPAP, and act as a liaison between the Awardee and the External Experts.
  • The NIH Project Scientist and Program Official will review the progress of HPPAP activities, and review the project for compliance with operating policies developed by the HIRN-AH Steering Committee, the HIRN consortia Steering Committees and the HIRN Trans-Network Committee. Based on this review, the Project Scientist in conjunction with the Program Official may recommend to the NIH to continue funding, or to withhold or restrict support for lack of scientific progress or failure to adhere to policies established by the HIRN Consortia Steering Committees and the HIRN Executive Committee. Review of progress may include regular communications between the Principal Investigator and NIH staff, periodic site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
• The NIDDK reserves the right to terminate the HPPAP award in the event of (1) A substantial shortfall in accomplishing the management goals and responsibilities stated in the funded application, (2) A failure to meet HIRN or NIH policies and procedures, (3) Substantive changes in the management of the HPPAP that are not in keeping with the objectives of the FOA.
• The NIH will enlist additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist 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 consultants involved in the project.
• The NIH Project Scientist will have substantial scientific programmatic involvement in coordination and performance monitoring of HPPAP activities. The dominant role and primary responsibility for these activities resides with the awardee, however, specific tasks and activities in carrying out the HPPAP functions will be shared among the awardee and the NIH Project Scientist.
• The NIH Project Scientist serves as a resource with respect to other ongoing NIH activities that may be relevant to HPPAP operations to facilitate compatibility and avoid unnecessary duplication of effort.
• The NIH Project Scientist may review procedures for assessing and monitor the performance of the HPPAP.
• The NIH Project Scientist may be a co-author 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.

Areas of Joint Responsibility include:

Through the Awardee and NIH staff, HPPAP will determine criteria and processes for quality control of information and data to be posted for the research community, consistent with NIH policies and achieving the goals of the program as described in the Funding Opportunity Announcement. There will be an annual face-to-face meeting of HPPAP and at least one other HPPAP meeting (teleconference or face-to-face meeting) annually. The HPPAP PD/PI, the HPPAP Project Scientist, the HPPAP Program Official and the Chair of the HPPAP Expert Scientific Panel are expected to attend these meetings.

Steering Committee

The HPPAP Awardee agrees to the governance of the HPPAP through a Steering Committee that is responsible for joint governance of the HIRN Administrative Hub (HIRN-AH).

• A Chairperson for the HIRN-AH Steering Committee will be chosen by the NIH. The Chairperson is responsible for coordinating the HIRN-AH Steering Committee activities, for preparing meeting agendas and for chairing meetings.
• The HIRN-AH Steering Committee will be composed at a minimum of its four voting members: the HIRN-CC PD/PI, the HIRN-BC PD/PI, the HPPAP PD/PI and the HIRN-CC Project Scientist. Other designated NIH program staff, HIRN-CC staff, HIRN-BC staff, HPPAP staff or external experts attending the Steering Committee meetings will be ex officio (non-voting) members. The HIRN-AH Steering Committee will meet at least bi-annually.
• All major scientific and policy decisions will be determined by voting policies as established by the HIRN-AH Steering Committee 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 HPPAP. Steering Committee activities and decisions will consider the advice of the HIRN consortia Steering Committees, the HIRN Trans-Network Committee and the External Experts.
• The HIRN-CC, HIRN-BC and HPPAP Project Scientists will help the HIRN-AH Steering Committee develop and draft operating policies.
• NIDDK staff, in concert with the HIRN-AH Steering Committee, will have the option to redirect research activities or operations being pursued within the HPPAP award if it is considered beneficial to the overall program.
• The awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the HIRN-AH Steering Committee. The HIRN-AH Steering Committee will report progress with regard to HPPAP activities at the Annual Investigator’s Retreat.

HIRN Trans-Network Committee (HIRN-TNC)

The HIRN-TNC will consist of: the PD/PI of the HIRN-CC, the PD/PI of the HIRN-BC, the PD/PI of the HPPAP and the Steering Committee Chairs and Project Scientists of the HIRN scientific topic consortia (CHIB, CTAR, CMAI, and CBDS); the TNC is not a governing body and does not cast votes.

The TNC will facilitate communication and foster collaboration across the different consortia.

The TNC will be responsible for organizing the yearly HIRN Scientific Investigator’s Retreat.

The TNC will meet by teleconference at least twice a year and will be organized by the HIRN-CC. Subcommittees of HIRN, as well as working groups for scientific planning may be established and require participation by HPPAP members through in-person, electronic, or teleconference meetings, as appropriate. The HIRN-CC is responsible for providing and maintaining a record of minutes of all TNC meetings, which will be approved by the TNC.

Expert Scientific Panel (ESP)

An independent panel of 2-5 External Experts will be appointed by the NIDDK and meet by teleconference with the HPPAP Project Scientist and the HPPAP Program Official at least once a year. The HPPAP-ESP will be updated on progress and give feedback to NIH on adjustments and future directions for HPPAP activities. On an annual basis, and following input from the HPPAP-ESP members, NIDDK staff will appoint a HPPAP-ESP Chair who will be required to attend the annual HIRN Investigator Scientific Retreat, to participate to the HIRN-AH Steering Committee meetings as ex-officio, and to serve as the HPPAP-ESP representative to the larger HIRN-ESP that will also meet once a year. All HPPAP-ESP members will also be invited to listen as ex-officio to HIRN-AH Steering Committee meetings. HIRN-CC will support costs for teleconferences between the HPPAP-ESP and the HIRN-AH Steering Committee, will arrange the HPPAP-ESP and HIRN-ESP teleconferences, maintain a record of minutes, and support costs for the HPPAP-ESP chair to participate in the annual HIRN Investigator Scientific Retreat.

Dispute Resolution

Disagreements that may arise in scientific/technical matter or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration after first attempting to resolve the issue through the Steering Committee or its subcommittees, as appropriate. An Arbitration 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 procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

Progress reports for multi-year funded awards are due annually on or before the anniversary of the budget/project period start date of award. The reporting period for multi-year funded award progress report is the calendar year preceding the anniversary date of the award. Information on the content of the progress report and instructions on how to submit the report using the RPPR are posted at http://grants.nih.gov/grants/policy/myf.htm.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

eRA Commons Help Desk (Questions regarding 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 CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Olivier Blondel
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-7334
Email: blondelol@niddk.nih.gov

Francisco O. Calvo, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8897
Email: calvof@mail.nih.gov

Craig Bagdon
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-0166
Email: bagdonc@niddk.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75. This FOA is supported under a Special Statutory Program for Type 1 Diabetes Research via PL 113-93 (Section 204), The Protecting Access to Medicare Act of 2014.