Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Funding Opportunity Title	Consortium on Human Islet Biomimetics (HIRN-CHIB) (UC4)
Activity Code	UC4 High Impact Research and Research Infrastructure - Cooperative Agreement Programs
Announcement Type	New
Related Notices	November 27, 2013 - See Notice NOT-DK-14-005. Notice of Correction to Award Budget.
Funding Opportunity Announcement (FOA) Number	RFA-DK-13-016
Companion Funding Opportunity	RFA-DK-13-013, U01 Research Project Cooperative Agreements RFA-DK-13-014, U01 Research Project Cooperative Agreements RFA-DK-13-015, UC4 High Impact Research and Research Infrastructure - Cooperative Agreement Programs RFA-DK-13-017, UC4 High Impact Research and Research Infrastructure - Cooperative Agreement Programs RFA-DK-13-018, UC4 High Impact Research and Research Infrastructure - Cooperative Agreement Programs
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.847
Funding Opportunity Purpose	This FOA invites new applications to participate in the Consortium on Human Islet Biomimetics (CHIB) that will support the development of a human islet microphysiological system or niche (a system that combines cells, cytoarchitecture, matrix, physical factors, secreted factors, etc.). CHIB will be part of the Human Islet Research Network (HIRN).

Posted Date	September 26, 2013
Open Date (Earliest Submission Date)	January 27, 2014
Letter of Intent Due Date(s)	January 27, 2014
Application Due Date(s)	February 27, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July, 2014
Advisory Council Review	October, 2014
Earliest Start Date	December 2014
Expiration Date	February 28, 2014
Due Dates for E.O. 12372	Not Applicable

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

This Funding Opportunity Announcement (FOA) requests applications for a new research consortium, the Consortium on Human Islet Biomimetics (CHIB) that will support the development of a human islet microphysiological system or niche (a system that combines cells, cytoarchitecture, matrix, physical factors, secreted factors, etc.). Biomimetics, the study of the formation, structure and function of biological systems, will facilitate the assembly of an in vitro system that closely mimics a functional human islet, by integrating stem cell biology, islet cell biology and tissue engineering. CHIB will be part of a collaborative research framework, the Human Islet Research Network (HIRN) that will include four research consortia, and an Administrative HUB composed of a Bioinformatics Center and a Coordinating Center. HIRN's overall mission will be to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. In order to maximize scientific exchange and accelerate research in that field, it is expected that all information, data, biomaterials, models, protocols, reagents, resources and methods developed by CHIB investigators will be shared not only within CHIB, but with other HIRN investigators, and with the research community.

The NIDDK Human Islet Research Network (HIRN)

Starting in 2014, and through a series of Funding Opportunity Announcements (FOAs), NIDDK will establish a new team science program, the Human Islet Research Network (HIRN), to help organize and support collaborative translational research related to the loss of functional beta cell mass in Type 1 Diabetes (T1D). HIRN will be jointly supported by NIDDK and the Type 1 Diabetes special funding program, and its overall mission will be 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. This program will be configured as a modular network of small research consortia, each defined by a specific set of research priorities. The network structure will help to facilitate interactions between small communities of investigators organized around common biological and/or technological challenges, with the overall goal of developing innovative strategies for the treatment, prevention and monitoring of T1D.

HIRN will be initiated through issuance of six related funding opportunity announcements, and will use a Cooperative Agreement funding mechanism. Two complementary initiatives will provide the administrative structure needed to support HIRN activities through the creation of an Administrative Hub (HIRN-AH) composed of a Coordinating Center (HIRN-CC; RFA-DK-13-013) and a Bioinformatics Center (HIRN-BC; RFA-DK-13-014). Four independent research initiatives will invite four founding consortia, each supporting investigator-initiated projects in the following areas: Targeting and Regeneration (CTAR; RFA-DK-13-015), Human Islet Biomimetics (CHIB; RFA-DK-13-016), Modeling Autoimmune Interactions (CMAI; RFA-DK-13-017) and Beta Cell Death and Survival (CBDS; RFA-DK-13-018).

All HIRN research initiatives will put a strong emphasis on human disease biology, the use of human cells and tissues, and the development of reagents, tools and disease-modeling platforms that can help further our understanding of the human disease process, or lead to innovative treatment strategies for patients with severely depleted beta cell mass. Beyond the set of six founding FOAs issued in 2014, it is anticipated that future HIRN initiatives will be issued in the future years, contingent on availability of funds, to support the evolution of the program over time, and in response to emerging scientific and technological advances.

Consortium on Human Islet Biomimetics (HIRN-CHIB)

Investigators have made great strides in recent years in generating human pancreatic progenitors in vitro from human pluripotent stem cells. The transplantation of human pancreatic progenitor cells derived from hESCs/iPSCs into a variety of NOD-SCID mouse models can lead to the formation of islet-like tissues containing beta cells with characteristics that are nearly identical to native human beta cells. However, these transplantation studies have limitations; they are slow and costly, and they may not predict responses in humans, accurately. The efficient generation of fully functional, appropriately, glucose-responsive insulin secreting beta-like cells, in vitro, remains elusive. One reason for the lack of success may be that the microenvironment of the islet is critical to the maturation and maintenance of human beta cells, in vitro. While at least one human beta cell line has been generated and human endodermal progenitor lines capable of differentiation into insulin-producing cells have been reported, these cells are difficult to grow under conventional 2D culture conditions. To date, maintenance of a mature adult human beta cell phenotype for long periods of time, in culture, has not been achieved using cells derived from human cadaveric islets. The use of human cell sources grown on an appropriately engineered platform that recapitulates the microenvironment of the islet, might support the maturation of islet cells, and better mimic the complex structure and physiology of a human islet, features that are likely critical for pancreatic beta cell health, in vitro.

The derivation of a bioengineered human islet that can mimic many of the features of a functional pancreatic islet, in conjunction with sensitive, quantitative assays of adult islet function, is the grand challenge of this initiative. Applications should address two major challenges in the field: 1) Derivation of an engineered platform that supports the maturation of islet-like structures from human pancreatic progenitor cells or 2) Maintenance of a mature and functional adult human beta cell phenotype for long periods of time in culture. Applications unresponsive to this FOA are those developing 3D tissues for transplantation, engineering non-human tissue models or developing simple 2D or 3D models that do not go significantly beyond those currently available and in use. Evidence of success in developing a human biomimetic system for at least one other organ/tissue is required.

If successful, human islet biomimetic systems could be used for 1) mechanistic studies of human beta cell maturation, replication, reprogramming, failure and survival, 2) the development of cell-based, in vitro models of human diabetes, including MODY, type 1 and type 2 diabetes, and 3) testing efficacy and toxicity of new therapeutics for diabetes. Once a human islet biomimetic system is created, the next challenge will be to develop an integrated microsystem platform that can incorporate several different modular biomimetic systems. These integrated microsystems should recapitulate the complex physiology and biology of the human body including vascularization and innervation, as well as hormonal, humoral and immunological signaling, actively being pursued by awardees from RFA-RM-11-022 Integrated Microphysiological Systems for Drug Efficacy and Toxicity Testing in Human Health and Disease (UH2/UH3) , and RFA-RM-12-001 Stem/Progenitor Cell-Derived Human Micro-organs and -tissues (U18).

Applicants are invited to participate in a coordinated research effort focused on human islet biology. Work will combine advances in beta cell biology, and stem cell biology, with the technological opportunities in tissue engineering related to materials science, microfabrication, and microfluidics technologies that have led to the generation of microdevices that support aspects of functional, living organs.

Applications should be multidisciplinary and propose teams with expertise in human stem cell biology, beta cell biology, diabetes, microfluidics, and microengineering. Several components will need to be considered in assembling a team, including the choice of an appropriate human cellular source. The human cellular source should be renewable; however, some of the initial development could use a non-renewable source such as cadaveric human islets. Applications should include the fabrication of the microengineered device, and well as the development of assays for assessing beta cell maturation and function, in vitro.

Research of interest includes the areas described above and the examples listed below. These are examples only and are not intended to be limiting.

• Microengineered devices that incorporate critical tissue-tissue interfaces, electrical activity, and the dynamic microenvironment of a pancreatic islet that could support the maturation of a human islet in vitro;
• Development of a microengineered device that supports long-term survival of adult human islets;
• Development of quantitative assays and discovery of biomarkers for assessing human beta cell maturation, and adult human beta cell function, in vitro;
• Microsystems engineering approaches to investigate complex interactions between tissue types, and to assess the effect of circulating nutrients and hormones during disease development and progression;
• Characterization of cell sources, preferably renewable, that could be used in creating a human pancreatic biomimetic device, including human pancreatic progenitors derived from human pluripotent stem cells. Consideration should be given to the choice of a single cell source if multiple cell types are needed to construct a human islet biomimetic device.

All methods, reagents, resources, biomaterials (including cells or cell lines), protocols, data and models developed by CHIB investigators are expected to be made available to the research community. Because the individual UC4 projects will be coordinated through CHIB, the timeline and processes for sharing within CHIB and with the community at large will be established by the CHIB NIDDK Project Scientist or the CHIB PD(s)/PI(s). All participants will be expected to adhere to these policies as a term of the award, consistent with achieving the goals of the program. Policy documents for CHIB will be accessible on the HIRN website.

MEETINGS OF CHIB AND HIRN

Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of CHIB must participate in an initial in-person HIRN meeting soon after awards are made, in the annual HIRN Investigator Scientific Retreat, as well as in CHIB teleconference meetings to be held at least biannually thereafter. All participants will be obligated to abide by the policies adopted by the majority vote of the CHIB Steering Committee. In the application, research project budget requests must include costs for the PD/PI and up to two other members of the individual project to attend both the initial in-person HIRN meeting and the annual HIRN Investigator's Scientific Retreat. The annual HIRN Investigator Scientific Retreat will last 2-3 days. All CHIB teleconferences will be organized and administered by the HIRN CC to coordinate the research projects to be conducted by the research grantees. Note that the CC will support costs of all CHIB and HIRN-related meetings except for costs for research project investigators to travel and attend the meetings.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIDDK intends to commit $9 million to fund 2-4 awards in FY 2014.
Award Budget	Application budgets are limited to $1.2 million per year in direct costs. This limit is inclusive of any direct and F&A costs associated with consortium or subcontract arrangements.
Award Project Period	The maximum project period is five years.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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, 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 Calvo, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard
Room 752, MSC 5452
Bethesda, MD 20892-5450
Telephone: 301-480-8897
Email: [email protected]

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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.The Biographical Sketch must include a Personal Statement that addresses experience that makes the investigator particularly well-suited for their role. For this FOA, this statement must address past collaborative interactions leading to research progress as evidence of the ability to participate in a consortium with shared and collaborative research projects and objectives.

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

• Budget requests must include costs for the PD/PI and up to two other members of the individual project to attend both the initial in-person HIRN meeting and the annual HIRN Investigator's Scientific Retreat.

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:

The applications sought in this FOA will propose to develop an in vitro microsystem that could be used for understanding human beta cell maturation, replication, reprogramming, failure, and survival, the development of cell-based models of human diabetes, and testing the efficacy and toxicity of new therapeutics for diabetes. To fully assess the potential of the applicant to address the research questions, additional submission requirements and information are requested to be included in the application.

Research Strategy: The application should include clear milestones and expected deliverables or outcomes relevant to the goals of this FOA for each year of the project. The Research Strategy section of the Research Plan is should include clear benchmarks or milestones of progress that will be reviewed by NIH as part of the non-competing award process.

The guiding principle of milestone-driven research is to remain focused on a well-defined goal, thus achieving that goal with greatest efficiency. The use of milestones provides clear indicators of a project's continued success or emergent difficulties. Milestones are different from specific aims. The milestones must provide objective and quantitative outcomes by which to justify advancing the project. The application must include a strong rationale for the choice of cell source, microsystem parameters, functional readouts, and quantitative go/no-go decisions to be made by those involved in the project, based upon accepted practices in the specific field. Once an application is funded, the milestones will be used to evaluate progress as part of the non-competing award process.

The Research Strategy sections should also include sections succinctly addressing: 1) How the islet biomimetic developed during the UC4 period will contribute to the overall goals of HIRN, and 2) Plans for regular meetings of CHIB involving key personnel and/or other appropriate researchers involved in the project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide with the following modifications:

• Intellectual Property Management Plan: A primary objective for CHIB is to develop broadly accepted models and standards that will be available to the community at large. Accordingly, awardees should manage intellectual property (IP) and data in a way that achieves this goal. The IP and data management plan may be included with the Data Sharing Plan.
• Restrictive licensing and sharing practices for CHIB data and resources could substantially diminish the value and public benefit. Management practices that would prevent or block access to, or use of CHIB project data and resources for research use will be considered to be hindering the goals of the CHIB and HIRN. Applicants are encouraged to clearly demonstrate in an IP Management plan how their strategies will achieve the desired public benefit and programmatic goals through effective sharing of CHIB data and tools.

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication.

Applicants should discuss the following:

• Availability of biological resources utilized and/or developed (cell lines, reporter systems);
• Availability of technologies and protocols developed with funds from this award.

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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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.

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 by the Center for Scientific Review and responsiveness by NIDDK, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

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

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

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

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

Significance

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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do PD(s)/PI(s) provide evidence of experience working productively in collaborative environments? Do PD(s)/PI(s) provide documented evidence of experience sharing data and reagents with the research community?

Innovation

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

Approach

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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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

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?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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 UC4, 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 awardee 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 Principal Investigator/Program Director (PI/PD) 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 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 Awardee will maintain the confidentiality of the information developed by the investigations, 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.
• Awardees 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 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 and with the HIRN-AH in all aspects of CHIB.
• Awardees must share data, materials, models, methods, information and unique research resources that are generated by the projects in accordance with CHIB policies in order to facilitate progress. When appropriate, and in accordance with NIH 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 of other CHIB members.
• Awardees will submit a list of milestones and project deliverables to the HIRN CC prior to the initial HIRN meeting, and will update this list annually.
• CHIB Awardees agree to establish agreements amongst themselves 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.
• Awardees agree 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 CHIB policies and procedures developed by the CHIB.
• Awardees must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.
• Upon completion or termination of the research project(s), the awardees 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 at the end of the study.
• Awardees may be asked by NIH staff to scientifically review applications for special opportunity pool funds, as deemed appropriate.

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 Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer 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 CHIB activities. The Expert Scientific Panel (ESP) will meet to review the progress of the research projects and to inform NIH staff of scientific developments and opportunities that may enhance the achievement of the study goals.
• 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 research projects, attend and participate in all meetings of the CHIB, and act as a liaison between the Awardee and the Expert Scientific Panel.
  • The NIH Project Scientist and Program Officer will review the scientific progress, cooperation in carrying out research, and maintenance of high quality research in each of the individual research project, and review the project for compliance with operating policies developed by the CHIB. Based on this review, the Project Scientist in conjunction with the Program Officer 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 CHIB. 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 or curtail any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or CHIB policy and procedure, (2) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or (3) concerns related to human subject safety that prompt the need for premature termination.
• The NIH Program Scientist and Program Officer will review applications for Special Opportunity Funds for responsiveness to program goals to insure that they are within the scope of CHIB research as described in the Funding Opportunity Announcement and NIH guidelines.
• 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 research coordination and performance monitoring. The dominant role and primary responsibility for these activities resides with the awardee, however, specific tasks and activities in carrying out the studies will be shared among the awardees 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 CHIB studies 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 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 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(s) and NIH staff, CHIB will cooperatively develop and implement processes to submit information and data to the HIRN-AH, 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 study, consistent with NIH policies and achieving the goals of the program as described in the Funding Opportunity Announcement.

There will be an initial face-to-face meeting of HIRN and a minimum of 2 CHIB meetings (teleconferences or face-to face meetings) annually. One of these bi-annual meetings could be combined with the annual HIRN Investigator Scientific Retreat. Awardee(s), the CHIB Project Scientist, and the CHIB Program Official are expected to attend these meetings. A team will be established through this program to enable multiple, but coordinated, approaches to advance this area of research. If a single award is made, then CHIB will be governed by the PI and the NIH Project Scientist.

Steering Committee

If multiple UC4s are funded, then CHIB Awardees agree to the governance of the study through a Steering Committee.

• On an annual basis, and following input from the CHIB Steering Committee members, NIDDK staff will appoint a Steering Committee Chair who will be in charge of facilitating the CHIB Steering Committee meetings and teleconference. In collaboration with the HIRN CC and the NIH Project Scientist, the Chairperson is responsible for coordinating the Steering Committee activities, for preparing meeting agendas and for chairing meetings.
• The Steering Committee, including the Project Scientist, is responsible for establishing and implementing processes and criteria for recommending special projects for consideration for special opportunity funds by NIH staff.
• The NIH Project Scientist may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees.
• The Steering Committee will be composed of the Principal Investigators/Program Directors for each UC4, or by UC4 representatives (one per UC4 grant) chosen by the Principal Investigators/program Directors in the case of multi-PI grants, and the NIH Project Scientist. Only the UC4 PI/PD or multi-PI UC4 representative and the NIH Project Scientist will be voting members of the Steering Committee and will attend all meetings of the Steering Committee. Each full member will have one vote. Other designated NIH program staff attending the steering committee meetings will be ex officio (non-voting) members. The CHIB Steering Committee will meet at least twice a year.
• All major scientific and policy decisions will be determined by voting policies as established by the 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 each individual project. Steering Committee activities and decisions will consider the advice of the External Experts.
• The NIH Project Scientist will help the Steering Committee develop and draft operating policies.
• NIDDK staff, in concert with the Steering Committee, will have the option to redirect research activities being pursued within the UC4 grant(s) 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 Steering Committee and Subcommittees.
• Awardees must serve on CHIB subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the HIRN Investigator Scientific Retreat.

HIRN Trans-Network Committee (HIRN-TNC)

The HIRN-TNC will consist of: the PI/PD of the HIRN CC, the PI/PD of the HIRN BC, 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 Investigator Scientific Retreat.
• The TNC will meet by teleconference at least bi-annually and will be organized by the HIRN CC. Meetings will be used to discuss and prioritize, and review the progress of applications that will use "opportunity pool" funds. Subcommittees of HIRN, as well as working groups for scientific planning may be established and require participation by the CHIB 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 EC meetings, which will be approved by the EC.

Expert Scientific Panel (ESP)

An independent panel of 2-5 External Experts will be appointed by the NIDDK and meet by teleconference with the CHIB Project Scientist and the CHIB Project Officer at least once a year. The CHIB-ESP will be updated on progress and give feedback to the CHIB PI/PD, Steering Committee and NIH on adjustments and future directions for the CHIB research projects(s). On an annual basis, and following input from the ESP members, NIDDK staff will appoint an ESP Chair who will be required to attend the annual HIRN Investigator Scientific Retreat, to participate in the CHIB Steering Committee meetings as ex-officio, and to serve as the CHIB-ESP representative to the larger HIRN-ESP that will also meet once a year. The CHIB-ESP Chair will be tasked with relaying the CHIB Steering Committee recommendations for new Opportunity Funds Initiatives to the HIRN ESP. All CHIB-ESP members will also be invited to listen as ex-officio to CHIB Steering Committee meetings. Members of CHIB-ESP may be asked, on an ad hoc basis, in the peer review of applications for new research applications that request opportunity pool funds. The HIRN-CC will support costs for teleconferences between the ESP and the CHIB Steering Committee, will arrange CHIB-ESP and HIRN-ESP teleconferences, maintain a record of minutes, and support costs for the CHIB-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 NIDDK 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 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)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

Sheryl M. Sato, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8811
Email: [email protected]

Francisco O. Calvo, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone 301-594-8897
Email: [email protected]

Craig E. Bagdon, MPA
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
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 Parts 74 and 92.