Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Type 2 diabetes (T2D) currently affects over 300 million people worldwide and its prevalence is increasing rapidly. T2D is characterized by insulin resistance, beta cell failure, dysregulated insulin secretion by pancreatic beta-cells, and additional metabolic disturbances. Dysglycemia along with other metabolic disturbances of T2D lead to significant complications due to end organ damage. Although the current rise in prevalence is driven by environmental factors such as life-style, it is now appreciated that complex genetic determinants contribute to an inherent susceptibility to T2D and its complications. Common and rare variant genome-wide studies and exome sequencing have yielded greater than 400 loci that have significant associations with T2D, related metabolic traits, and/or diabetic complications. For the purposes of this RFA, the terms disease and trait are used broadly, to encompass diseases, risk of diseases, protective effects against diseases, complications, molecular phenotypes, organismal phenotypes, clinical phenotypes or outcomes, responses to therapeutic drugs, and other outcomes relevant to human health and disease.

Translation of many of these disease-associated risk loci to causal variants and their downstream effector transcripts (coding or non-coding) has been complicated by the fact that the risk loci often lie in non-coding regions of the genome, far from the effector transcript they regulate. Through work accomplished by the AMP T2D Consortium, an unprecedented amount of human genomic and epigenomic data around T2D have been collated and analyzed, leading to the initial identification of over 130 possible effector transcripts . While many probable effector transcripts have been identified, in many cases their causal role has not yet been validated nor their, mechanism of action determined, and their full impact on traits has not been elucidated. At the same time, there remain significant amounts of genomic information around T2D and its complications that can be added to the AMP T2D KP as well as additional omics and other data types that can be incorporated or integrated into its existing foundation.

To address these gaps, the NIDDK is soliciting applications to this RFA and its companion RFA (RFA-DK-19-505) to address the overarching goals of 1) accelerating the pace of understanding of the genetic architecture of T2D and its complications, 2) identifying effector transcripts with predicted causal relationship to T2D and its complications, 3) validating the strength of predicted effector transcripts through experimental work and their placement in networks, and 4) making this information broadly available to the scientific community to foster fundamental and clinical research ultimately resulting in the identification of potential biomarkers for disease and the discovery of potential therapeutic targets. To accomplish these goals awardees to the AMP T2D KP (RFA-DK-19-505) and Functional Genomic Projects (FGPs; RFA-DK-19-012) will continue the AMP T2D Consortium, working together toward the overarching goals.

Goals and Objectives of the Functional Genetics Projects

The overall goal of the Functional Genomics Projects (FGPs) will be to develop a functional understanding of the causal variants, effector transcripts, and regulatory networks that emerge from elucidating the genetic architecture of T2D, its complications, and relevant traits. In GWAS and whole-genome sequencing projects, most of the disease- and trait-associated variants fall outside coding regions, are likely involved in gene regulation in specific cell types, and usually cannot be interpreted without substantial functional data. Even in situations with a higher likelihood of a variant being causal, such as a missense variant in a protein-coding region, the functional significance of this variant generally cannot be determined with available data. When variants in known disease- or trait-associated regions of the genome are studied, it can be unclear how they contribute to phenotypes without substantial confirmatory efforts in model systems. Thus, precisely defining the contributions and underlying mechanisms of T2D risk variant loci will further the understanding of genetic impact on the disease and aid in the identification of new targets and biomarkers for the prevention and treatment of T2D and its complications. The purpose of the FGPs will be to generate novel data, tools, and models for use by themselves and the broader scientific community to achieve these goals. Awardees to the FGPs will work closely with each other and the AMP T2D KP to meet common objectives and facilitate data deposition, integration, and visualization.

Overview

The FGPs will accomplish their goals by systematically generating novel data in a high- to medium-throughput manner to assess the functional importance of all T2D risk variants and downstream predicted effector transcripts identified by the FGP awardees and the AMP T2D KP. An initial list of predicted effector transcripts has been identified by the AMP T2D partnership and they are listed below. This includes those with known causal roles in T2D as well as sets ranging from strong to weak evidence for a causal role in T2D and a set with evidence for associations with traits related to T2D. The HUGO Gene Nomenclature Committee symbols for the predicted effector transcripts identified at publication of this RFA and that are expected to serve as initial candidates in applications to this RFA are:

Causal: ABCC8, ANGPTL4, ANKH, APOE, CDKN1B, GCK, GCKR, GIPR, GLIS3, GLP1R, HNF1A, HNF1B, HNF4A, IGF2, INS, IRS2, KCNJ11, LPL, MC4R, MNX1, MTNR1B, NEUROG3, NKX2-2, PAM, PATJ, PAX4, PDX1, PLCB3, PNPLA3, POC5, PPARG, QSER1, RREB1, SLC16A11, SLC30A8, SLC5A1, TBC1D4, TM6SF2, WFS1, WSCD2, ZNF771

Strong: ABCB9, BCAR1, C2CD4B, CAMK1D, CCND2, DGKB, INSR, IRS1, IRX3, IRX5, KLF14, KLHL42, LMNA, SLC2A2, STARD10, TCF7L2, ZMIZ1

Moderate: ADCY5, AGPAT2, AGTR2, AP3S2, BCL11A, CISD2, FAM63A, FOXA2, GPSM1, IGF2BP2, JAZF1, KCNK17, MACF1, MADD, NKX6-3, PDE8B, PLIN1, SGSM2, SPRY2, UBE2E2, VPS13C

Possible: ANK1, ASCC2, CALCOCO2, FADS1, HMG20A, IL17REL, MRPS30, PRC1, PTRF, SCD5, SNAPC4, ST6GAL1, TP53INP1

Weak: ABO, CARD9, CDK2AP1, CTNNAL1, DNZL, ITGB6

Related Traits: ADRA2A, AKT2, APPL1, BLK, BSCL2, CAV1, CEL, EIF2AK3, ERAP2, FOXP3, G6PC2, G6PD, GATA4, GATA6, GCG, GRB10, IER3IP1, IGF1, KLF11, NAT2, NEUROD1, PAX6, PCBD1, PCSK1, POLD1, PPP1R15B, PTF1A, RFX6, SIX2, SIX3, SLC19A2, TRMT10A, WARS, ZFP57

Because different variants (e.g., common vs. rare or coding vs. non-coding) often require different approaches of study, the FGPs should encompass a wide array of experimental approaches amenable to risk variants and their downstream effectors. For instance, variants in protein-coding regions may involve characterization of protein products in vitro, in cell lines, or in transgenic animals. The interrogation of variants in non-coding regions may involve the analysis of sequence conservation, expression or protein quantitative loci (e/pQTL) analyses, and/or assessment of chromatin modifications at regulatory sites. Computational approaches will be required to prioritize the discovered variants for lower throughput functional studies. Integrative analyses will then facilitate the identification of key signatures, specific cell subsets, and/or biological networks to be mined for potential therapeutics and biomarkers. The proposed research is expected to utilize human tissues or cells from well-characterized individuals. Animal studies, if included, should be complementary to the proposed human research and address mechanistic or therapeutic questions that cannot be addressed directly in humans.

Potential research approaches include but are not limited to:

• Fine mapping and sequencing of a targeted human genomic region(s), including coding and non-coding;
• Studies exploiting genetic methodologies in concert with other methods, such as functional genomics, in silico mapping data, and/or gene expression profiling, to identify epigenetic/genetic variants and predicted effector transcripts;
• Approaches that consider how factors such as time of effector transcript expression (development -> adulthood -> aging) and various types of perturbations (e.g., interactions with the environment, diet, infections) influence mechanisms underlying disease-relevant traits;

• Integrative analyses of multidimensional datasets such as genetics, genomics, transcriptomics, proteomics, metabolomics, and/or phenomics to identify key signatures, specific cell subsets, and/or biological pathways for further functional validation;
• Assessment of the biological function of a particular genetic variant(s) in cells or tissue based in vitro model systems or animal models.

Below are types of projects that are not responsive to this RFA :

• Clinical trials are not responsive to this FOA;
• Initial discovery Genome Wide Associated Studies (GWAS) or sequencing efforts;
• Simple replication of initial genomic findings.

Identification of Predicted Effector Transcripts

A major challenge in moving from disease and trait risk variants for T2D and its complications to disease understanding and potential therapeutics and biomarkers is identifying the causal effector transcripts associated with variants. This is complicated by factors such as pleiotropy of causal variants around risk loci, the complexity of transcriptional regulatory machinery, and cell type and cell state specific regulatory environments. While an initial list of predicted effector transcripts has been identified by the AMP T2D KP, there remains a significant number of risk variants for which downstream effectors have not been predicted as well as genomic risk variants for T2D, complications, and related traits that have not yet been identified. FGP applications should include a detailed description of a proposed experimental and computational pipeline to predict new effector transcripts, including initial genomic risk variants that will serve as starting points in the pipeline. Additional genomic risk variants in future years may be identified by applicants to this solicitation and/or in collaboration with the AMP T2D KP and other Consortium members. This component of the FGPs should focus on the use of existing tools, models, and technologies rather than developing new ones. It is expected that this pipeline will undertake research approaches such as, but not limited to:

• Systematic mapping of transcription factor and microRNA binding sites or chromatin modifications in cell types and states relevant to T2D and its complications;
• Studies to identify non-coding RNAs relevant to diabetes;

• The use of high-throughput approaches such as CRISPR modification of cell models for rapid phenotype screening and/or regulatory mapping;

• Moderate throughput uses of non-mammalian models or biomimetic systems to assess and prioritize focused numbers of predicted effector transcripts.

Evaluation of Predicted Effector Transcripts

Applications for FGPs must include an approach that uses high- to medium-throughput assays in a variety of models to test the validity of predicted effector transcripts and generate novel data around the genetic, cellular, and physiological networks in which they function. Initial studies should include effector transcripts predicted by the current AMP T2D KP (listed above). As these approaches will utilize assays of varying throughput and complexity, a funneling approach in which predicted effector transcripts are first prioritized through higher throughput approach(s) should be utilized. Use of model organisms or model systems is encouraged, especially where approaches are especially suited for these systems; however, information forthcoming from these models should be relevant to humans. It is expected that this component will undertake research approaches such as, but not limited to:

• Functional validation studies using phenotypically well-characterized individuals to correlate variants in effector transcripts with a relevant trait;
• Identification of protein-protein interaction networks for proteins encoded by predicted effector transcripts;
• Evaluation of functional impact of variants on protein activity or abundance.

Data and Network Analysis and Modeling

Applications for FGPs must include a component that describes how all data types generated by their experimental efforts will be analyzed, integrated, and visualized. This component should also have the capability to place validated effector transcripts, using associated data, in to networks that generate testable hypotheses about their role and importance in T2D and its complications. A goal of this network modeling should be to identifyg key network nodes that could serve as the basis for future therapeutics or biomarker discovery. The goal is to identify key nodes regardless of their current druggability as future technologies and approaches may expand what is considered druggable. Awardees are expected to make all data, software tools, and analyses publicly available, using existing repositories when possible. It is expected that this component will undertake research approaches such as, but not limited to:

• Develop novel computational methods to integrate functional data and other data types to help to understand which variants are causal for a phenotype;
• Develop novel computational models explaining how variants lead to differences in function in relation to phenotypes;
• Identify key modulatory nodes within networks that drive the emergence of traits relevant to T2D and its complications;
• Build a framework to understand the contribution of interacting networks based on causal effector transcripts to disease heterogeneity within individual patients.

Organization and Management of the FGPs

Applicants are strongly encouraged to seek multidisciplinary collaborations to ensure the inclusion of appropriate expertise for the proposed studies. Applications are expected to reflect integration of relevant groups such as clinicians, geneticists, basic cell biologists, computational scientists, systems biologists, statisticians and data scientists. Such an integrated effort will ensure that the complexities of phenotypic definition, the study design, the technical approaches, methods and model systems, the power and statistical genetic analysis are adequately considered. Awards under this FOA will provide support for personnel, analyses, functional studies and other costs, as justified by the study design. This FOA will not support initial discovery GWAS/sequencing efforts or simple replication of initial genomic findings. This FOA will not support the recruitment of a new cohort of human subjects or clinical trials. The new collection of biological samples, or new collection of phenotypic, environmental, or other medical data will be permitted in a targeted approach relevant to the investigation of selected variants. Additional personnel may be supported for sample and data handling.

Investigators selected through this FOA will comprise a Consortium along with investigators to AMP T2D KP (RFA-DK-19-505). The Consortium may include additional investigators funded by the NIDDK or AMP T2D funding partners. A Steering Committee will be established to oversee the governance of this Consortium.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) 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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed ?with the following exceptions or additional requirements:

The Research Strategy section is limited to 30 pages and must consist of the following subsections with the indicated page limits:

• Sub-Section A. Overview
• Sub-Section B. Identification of Predicted Effector Transcripts
• Sub-Section C. Evaluation of Predicted Effector Transcripts
• Sub-Section D. Data and Network Analysis and Modeling

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.

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

The following additional budget-related information must be included:

• Applicants must budget funds for travel for at least one PD/PI to attend an annual 2-day meeting of the AMP T2D Consortium in the Washington, D.C. area.

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 Research Strategy must consist of the following subsections A D, as defined below, uploaded as a single PDF attachment.

Sub-Section A. Overview: The Overview should consist of a summary of the overall scientific approach to be undertaken in the proposed FGP. This should include a description of the workflow that will be undertaken to move from risk variants for T2D and its complications using the approaches detailed in sub-sections B, C, and D.

Address, at a minimum, the following aspects:

• An assay flowchart explaining how higher throughput assays will be used to explore hundreds of risk variants, prioritize predicted effector transcripts for study, and further prioritize select effector transcripts for more detailed validation;
• How the workflow will be used in an iterative fashion as new risk variants and predicted effector transcripts are identified and how the workflow will be refined as the project moves forward;
• A research management plan that describes how data will be shared across investigator sites and how day-to-day operations of the project will be managed;
• Overall project deliverables, timelines, and milestones;
• A statement of willingness to work with other members of the consortium and the SC to collectively identify prioritized risk variants and effector transcripts for study.

Sub-Section B. Identification of Predicted Effector Transcripts: This section should explain the experimental approaches to be used to move from risk variants to predicted effector transcripts.

Address, at a minimum, the following aspects:

• Details of proposed experimental approaches and how they fit in to the overall workflow of the FGP;
• Cell types and source and their relevance to the study of T2D and its complications;
• If applicable, proposed animal models should be fully described and include rationales for their importance to the proposed studies and relevance to human disease processes.
• Estimates of the throughput of the assays and the number of risk variants that can be studied per year;
• An estimate of the number of predicted effector transcripts to be identified;
• A list of the initial set of risk variants for T2D and its complications that will be used as starting points in the first year of studies;
• The flexibility of the platform to accommodate emerging risk variants in future years.

Sub-Section C. Evaluation of Predicted Effector Transcripts: This sub-section should describe the experimental approaches to be used to evaluate and determine the functional roles of predicted effector transcripts.

Address, at a minimum, the following aspects:

• Details of proposed experimental approaches and how they fit in to the overall workflow of the FGP;
• Cell types and source and their relevance to the study of T2D and its complications;
• If applicable, relevance of proposed animal models to human disease processes should be addressed.
• Estimates of the throughput of the assays and the number of predicted effector transcripts that can be studied per year;
• An initial set of predicted effector transcripts for T2D and its complications to be used as starting points in the first year, to include at least 25 predicted effector transcripts from the Strong, Moderate, Possible, Weak, and/or Related Traits categories listed above under Goals and Objectives of the Functional Genetics Projects ;
• The flexibility of the platform to accommodate emerging predicted effector transcripts in future years;
• A statement of willingness to work with the Consortium to determine high priority effector transcripts for study.

Sub-Section D. Data and Network Analysis and Modeling: This sub-section should identify the computational approaches that will be used to analyze data that emerge from work proposed in Sub-Sections B and C.

Address, at a minimum, the following aspects:

• The computational approaches that will be used to place the validated effector transcripts resulting from the studies described in Sub-Section C into network models;
• How emerging experimental results will be used to refine analysis and network models;
• Approaches to identify key nodes that may serve as readouts for biomarkers or as modulation points for potential therapeutics should be described;
• Preliminary data demonstrating sufficient expertise to develop analytical and visualization tools for the data types generated in sub-sections B and C;
• A statement of willingness to work with awardees to the AMP T2D KP to incorporate select analytical and visualization tools into the Knowledge Portal.

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

The following modifications also apply:

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

• Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the Consortium SC and approved by NIH staff. A primary goal of the AMP T2D program is to facilitate discoveries of the broad scientific community for the improvement of public health. Restrictive licensing and sharing practices for Consortium-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of AMP T2D data, tools, and resources for research purposes will be considered to be hindering the goals of the program. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, through the Consortium SC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.

• Specific Plan for Data Sharing: Consistent with achieving the goals of this program, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. Data should also be made available as appropriate via the AMP T2D Knowledge Portal that will serve as the central access point for information regarding data, critical tools, and reagents being developed by the Consortium. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/) and should indicate their agreement to it in the data sharing plan.

• Specific Plan for Protocol, Tool, and Reagent Sharing: In accomplishing the goals of the AMP T2D program, it is likely that investigators will develop protocols, tools, and reagents that would be of broad use in the research community. The NIH intends that protocols, tools, and reagents generated by the AMP T2D be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream investigations of T2D-relevant risk variants and effector transcripts by the larger scientific community. For all applications where applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including models, protocols, biomaterials, and reagents.

• Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in applications that are developing software. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan. A dissemination plan guided by the following principles is thought to promote the largest impact:

  • The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.

  • The terms should permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.

  • The software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

  • The terms of software availability should include the ability of researchers outside of AMP T2D and its collaborating projects to modify the source code and to share modifications with other colleagues. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software.

• Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).

• Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

Important reminders:

All PD(s)/PI(s) 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Section V. Application Review Information

1. Criteria

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the 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? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Specific to this FOA: Will the successful completion of the aims of this project lead to a significant advancement in the understanding of the function of risk variants and their downstream effectors for type 2 diabetes and its complications?

Investigator(s)

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

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

Specific to this FOA: Does the application contain an effective strategy to identify new predicted effector transcripts and does this strategy include an appropriate plan to mine novel genomic risk variants for type 2 diabetes and related traits? Have the applicants proposed an appropriate strategy to evaluate and determine the functional roles of predicted effector transcripts? Are the use of the cellular and/or animal models proposed sufficiently justified and appropriate for the proposed studies? Does the assay flowchart explain how higher throughput assays will be used to explore hundreds of risk variants, prioritize predicted effector transcripts for study, and further prioritize select effector transcripts for more detailed validation? Have the applicants adequately described how this assay pipeline will be iterated through during the multiple years of the project? Are the computational approaches that will be used to place validated effector transcripts into network models and use these network models to identify key nodes appropriate and incorporate adequate plans for iterative refinement?

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 individuals of all ages (including children and older adults), 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?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

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) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 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.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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.

2. Administrative and National Policy Requirements

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

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

The Consortium will be made up of awardees to RFA-DK-19-012 and to RFA-DK-19-505 (Knowledge Portal), NIH staff that are primarily responsible for the stewardship of these awards, other scientists and groups the Steering Committee (see below) agrees to include within the Consortium, and, possibly, additional AMP T2D funding partners and awardees. The Consortium structure is meant to enable the overall goals of the AMP T2D program.

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

• Awardee(s) will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• The Program Director/Principal Investigator (PD/PI) will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement (FOA) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
• Awardee(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.
• Awardee(s) are responsible for their staff in maintaining confidentiality of the information as developed by the consortium, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the Steering Committee (SC) as well as any confidential information received by third party collaborators.
• Awardee(s) must analyze, publish and/or publicly release and disseminate results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and achieving the goals of the FOA.
• Awardee(s) will be required to participate in a cooperative and interactive manner with members of the consortium including designated NIH staff (e.g., Program Official, Project Scientist).
• Awardee(s) are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis and (2) for clinical studies, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense.
• Awardee(s) must share data, materials, models, methods, information and unique research resources that are generated by the projects in concordance with Consortium policies in order to facilitate progress. When appropriate, and in accordance with NIH policies, as well as NIDDK policies, awardee(s) 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 Consortium members.
• Awardee(s) 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 bio-specimens 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.
• Awardee(s) agree that each industry collaboration should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH policies and procedures.
• Awardee(s) must agree to comply with the processes and goals as delineated within the FOA.
• Upon completion or termination of the research project(s), the awardee(s) 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.
• Awardee(s) agree to the governance of the study through a Steering Committee:
  • The PD/PI, r contact PD/PI in the case f multi-PD/PI awards, will serve as a voting member of the Steering Committee and will attend all meetings of the Steering Committee.
  • Each full member will have ne vote.
  • The awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and Subcommittees.
  • Awardee(s) must serve n Consortium subcommittees as needed. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator’s Retreat.

• Awardee(s) may be asked to scientifically review applications for special opportunity pool funds, as it is 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 Official and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award.
• The NIDDK will invite External Consultants with relevant scientific expertise. The External Consultants will meet to review the progress of the research projects and to advise NIH staff of scientific developments and opportunities that may enhance the achievement of the study goals.
• An NIH IC Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows:

• The NIH Project Scientist(s) will coordinate and facilitate the research projects, attend and participate in all meetings of the Consortium Steering Committee, and act as (a) liaisons between the Awardee(s) and the External Consultants.
• The NIH Project Scientist(s) will be a member(s) of the Steering Committee and, as determined by that committee, and its Subcommittees as needed. Only ne NIH Project Scientist will vote on the Steering Committee. Other designated NIH program staff attending the steering committee meetings will be an ex officio (non-voting) member(s).
• The NIH Project Scientist, and other designated NIH program staff will help the Steering Committee develop and draft operating policies.
• The NIH Project Scientist(s) and Program Official will review the scientific progress, cooperation in carrying out research, and maintenance of high quality research in each of the individual research projects, and review the projects for compliance with operating policies developed by the Consortium Steering Committee, and may recommend to the NIH to continue funding; withheld support or restrict an award for lack of scientific progress or failure to adhere to policies established by the Consortium Steering Committee. Review f progress may include regular communications with the PD/PI and NIH staff, periodic site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of periodic external review of progress.
  • The NIDDK reserves the right t terminate or curtail any study or any individual award in the event of (a) substantial shortfall in data collection or submission, quality control, or other major breach or a study protocol or Consortium policy and procedure, (b) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, and/or a human subject ethical issues that may dictate a premature termination.
• The NIH Project Scientist(s) and Program Official will review and approve applications of the Special Opportunity Funds to ensure that they are within the scope of Consortium research as described in the FOA and NIH guidelines.

• The NIH will name additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist(s) and the Steering Committee in carrying out the goals and aims of the approved studies. The NIH will have ne vote for any key committees, regardless of the number of NIH personnel involved.
  • The Project Scientist(s) will have substantial scientific programmatic involvement in quality control, preparation of publications, research coordination and performance monitoring. The Project Scientist(s) will have the same access and privileges to any data generated by the grantee. The dominant role and primary responsibility for these activities resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardee(s) and the NIDDK Project Scientist(s).
• The NIH Project Scientist(s) serve as a resource with respect to other ongoing NIH activities that may be relevant to the Consortium’s studies to facilitate compatibility and avoid unnecessary duplication of effort.

• The NIH Project Scientist(s) or designee may coordinate activities among awardee(s) by assisting in the design, development, and coordination of (a) common research protocol(s) and statistical evaluations of data and in the publication of results.

• The NIH Project Scientist(s) may review procedures for assessing data quality and monitor study performance.

• The NIH Project Scientist(s) may be (a) co-author(s) on study publications. In general, t 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 Steering Committee, the awardee(s) and NIH staff will cooperatively develop and implement processes to submit information and data to the Knowledge Portal (KP) 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 FOA.

Steering Committee (SC)

• The Steering Committee (SC) composed of each of the PD/PI(s) fr each UM1, or Contact PD/PI(s) in the case f multi-PD/PI grants, of the study (including research projects and Knowledge Portals) and the NIH Project Scientist(s) will be the main governing board of the study Consortium. Each full SC member will have one vote. All major scientific and policy decisions will be determined by (voting policies as established by the SC at the initial meeting). This committee will operate to develop collaborative protocols, identify impediments to success and strategies to overcome them, develop shared tools for disseminating information about the projects, and identify opportunities for sharing techniques, materials, information and tools developed within each individual project. The SC activities and decisions will consider the advice of the External Consultants.
• NIDDK staff, in concert with the SC, will have the option to redirect research activities within the UM1 grant(s) if it is considered beneficial to the overall program.
• The SC may, as it deems necessary, invite additional, non-voting scientific consultants to meetings at which research priorities and opportunities are discussed. The NIH reserves the right t augment the expertise of the Steering Committee when necessary.
• There will be (an initial) meeting and Consortium Steering Committee meetings annually. These meetings will incorporate participation and recommendations of the External Consultants when determined by NIH staff (or as stipulated in the FOA).
• An SC Chairperson will be chosen by the NIH. In collaboration with the Knowledge Portal and the NIH Project Scientists, the Chairperson is responsible for coordinating the SC activities, for preparing meeting agendas and for chairing meetings.
• The SC, including the Project Scientist(s), is responsible for establishing and implementing processes and criteria for recommending special projects for consideration for special opportunity funds by NIH staff.
• Each research project awardee and the Knowledge Portal awardee agree to the governance of the UM1s through the SC.
• The NIH Project Scientist(s) may work with awardee(s) on issues coming before the Steering Committee and, as appropriate, other committees.

External Consultants

• Independent External Consultants will be identified by the NIDDK. The External Consultants will review periodically interim progress of the UM1s and report to NIDDK staff. External Consultants may be asked, on an ad hoc basis, to participate in the peer review of applications for new research initiatives that utilize special opportunity pool funds.

Dispute Resolution:

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

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

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

Norann Zaghloul, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-6677
Email: [email protected]

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

Craig E. Bagdon
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
Email: [email protected]

Section VIII. Other Information

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.