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

Recent significant advances in genetics, physiology, and the pathogenesis of disease coupled with technological advances in areas such as bioinformatics, chemical biology, non-mammalian disease modeling, and protein engineering have provided a rich knowledge base and strong toolbox to identify and pursue new therapeutics with the goal of generating new molecular, microbial, and cellular therapies for the treatment of disease. Despite the availability of these approaches, we are facing an increased failure rate of potential therapeutics for reasons of both safety and lack of human efficacy. A critical need exists to develop better strategies to validate and prioritize therapeutic leads based on their likelihood of success to safely alter disease progression and outcomes in humans.

Projects submitted to this FOA should be directly focused on a therapeutic lead that will modulate a health-related outcome of interest to the NIDDK. Prior to submitting an application, investigators are strongly encouraged to contact the Scientific/Research Contact for this FOA to discuss the appropriateness of the proposed research to this FOA. Information concerning programmatic areas at NIDDK is available at: www.niddk.nih.gov/research-funding/research-programs/Pages/default.aspx. Projects in areas that are primarily within the missions of other Institutes or Centers (ICs) of the NIH are not appropriate for this FOA and will not be supported.

Staging of Therapeutic Discovery and Validation

The process of identifying and validating therapeutic leads such as small molecules or non-viral biologics for the treatment of human disease begins with a hypothesis and can be viewed as progressing along a continuum of increasing confidence leading to widespread acceptance of its use in people (www.niddk.nih.gov/research-funding/process/translational-research-therapeutic-discovery-development/Pages/default.aspx). For the purposes of this FOA, these stages are defined as:

Identification of therapeutic leads: This may occur through a variety of approaches and stages such as identifying targets, screening compound libraries, or constructing prototype non-viral biologics with preliminary evidence that they may significantly impact a disease process.

Early-stage preclinical validation: Pre-clinical hypothesis testing to generate data that, over time, increases confidence that manipulation of disease processes via a specific therapeutic strategy may be clinically efficacious and safe. This process occurs prior to clinical testing of a new therapeutic, and ideally should include the use of human-derived data, tissues, cells, and systems.

Clinical validation: Studies conducted in human patient populations to fully understand the efficacy and safety profiles of a therapeutic agent. True validation of a therapeutic agent may take decades of post-regulatory approval data accumulation.

This FOA is intended to stimulate research that furthers early-stage preclinical validation of therapeutic leads to a point where there is sufficient scientific evidence to justify larger scale therapeutic discovery and development efforts. It is NOT intended to support target identification, identification of therapeutic leads, or clinical target validation. Later stage therapeutics discovery and development efforts may be pursued via mechanisms outside of this FOA such as, but not limited to, spin-off companies, licensing to or partnering with pharmaceutical companies, other funding opportunity announcements, and non-profit organizations.

Examples of the level of early-stage small molecule or non-viral biologic validation intended to be pursued under this funding opportunity include, but are not limited to:

• Elucidation of the initial structure-activity relationship and absorption, distribution, metabolism, excretion, and toxicity properties of a small molecule to demonstrate its in vivo potential for further optimization;
• Providing strong data, using well validated and predictive animal and/or human tissue-based models, that there is a high likelihood that a therapeutic lead will treat a disease.

This funding opportunity announcement extends the knowledge of early-stage preclinical validation of novel small molecules and novel non-viral biologics that are not the focus of significant efforts in the biotechnology and pharmaceutical industry for treatment of diseases within the mission of the NIDDK. This includes therapeutics targeted to outcomes relevant to obesity, diabetes and related aspects of endocrinology and metabolism, digestive diseases, liver diseases, nutrition, kidney and urological diseases, hematology, and specific aspects of cystic fibrosis.

Particular areas of interest include, but are not limited to:

• Pharmacological testing of therapeutic leads coupled with the evaluation of novel non-mammalian animal models (e.g. zebrafish, Drosophila) to predict the efficacy and safety of compounds;
• Medicinal chemistry efforts to understand the structure activity relationships of small molecules, including prebiotics and microbiome-derived metabolites, to improve their use as early therapeutic leads, possibly including initial characterization of absorption, distribution, metabolism, excretion, and toxicity properties;
• Ex vivo engineering of cellular or tissue constructs, probiotic or commensal microbes, or consortia of these microbes, and assessing the efficacy and safety of their transplant in preclinical disease models;
• Assessment of interaction of probiotic or novel microbiome-derived therapeutic strains with the resident microbial community using in vitro bioreactors or gnotobiotic animals;
• Generation of a therapeutic lead protein and its use in proof of concept studies in animal and/or human tissue-based models of disease;
• The development and use of nanotechnology, bioinspired materials, or other methods in conjunction with molecular optimization to result in significant enhancements to the potential therapeutic properties of the therapeutic lead (e.g. organ- or cell-type specific targeting, prolonged half-life, environment-sensitive compound release).

The following are types of applications that are NOT appropriate for this FOA:

• Applications for which prototype therapeutic leads have not yet been identified (e.g. assay development projects, high throughput screening of large small molecule libraries, fractionation of natural products);
• The development of novel tools, models, or technologies without an integrated plan for their use in target, small molecule, or non-viral biologic target validation;
• Research focused on understanding normal biology or disease processes;
• Projects in which the primary focus is medicinal chemistry or protein engineering without an integrated plan to evaluate the validity of the target for a health-related outcome within the mission of the NIDDK;
• Applications primarily focused on identifying new targets.

Mechanisms of action of therapeutic leads

The mechanism(s) of action of therapeutic leads supported by this FOA under some circumstances do not need to be fully elucidated. This may be particularly true of projects using non-mammalian organisms in which the pleiotropic effects of a compound on multiple interlinked physiological systems or engineering tissue constructs where secretion of cellular factors and cell-cell interactions are likely to be key drivers of efficacy. All projects should explore efficacy and safety of the therapeutic leads, but for certain aforementioned projects they do not need to fully elucidate their mechanisms of action. Additionally, this FOA is NOT intended to support the basic understanding of disease or therapeutic lead processes, but may conduct mechanistic studies related to evaluating efficacy and safety.

Technical Aspects around Therapeutic Leads

1. Prototype therapeutic lead. The starting points for medicinal chemistry optimization or protein or cellular engineering may have been selected through many approaches such as screening in non-mammalian organism assays, fractionation of natural products, high throughput screening, phage display libraries, etc. Initial prototypes should be well characterized with, when appropriate, a clear path forward for the generation and/or synthesis of more advanced derivates. In some cases the proposed therapeutic lead may itself be a candidate for further development. Examples of types of characterization around a therapeutic lead are:

• Demonstration of a reproducible response within the assays proposed for further evaluation/optimization;
• Analytical data showing appropriate quality, identity and suitability of the therapeutic lead;
• When appropriate, the suitability to serve as a tractable starting point for optimization;
• How the therapeutic lead is relevant to the mission of the NIDDK.

The submission of applications with back-up prototype therapeutic leads is encouraged to increase the overall likelihood of a successful project.

2. Assays. Established in vitro and/or in vivo assays should be used to support optimization of prototype therapeutic leads and continued preclinical validation. Such assays should exhibit reproducible behavior in response to prototype therapeutic leads and, where possible, appropriate comparators.

The co-development of new assays (e.g. next-generation animal models, microfluidic-based 3D human organoid systems) may occur alongside the benchmarking of more established assays.

3. Emerging technologies. The emergence of truly novel therapeutics may necessitate new approaches. The co-development of these technologies, tools, and models as well as the exploration of new chemical and biological space in direct support of therapeutic lead validation efforts within an application is appropriate. Examples of such approaches are:

• The co-development of new technological approaches for validating therapeutic leads;
• New models that recapitulate better the human disease state or susceptibility to toxic effects;
• Accessing new molecular space for the identification of new classes of small molecules or the generation of new approaches to non-viral biologic therapeutics in order to find compounds specific for novel targets.

Applications may propose interaction with NIDDK-funded existing research consortia, such as the Human Islet Research Network (hirnetwork.org), the Rebuilding a Kidney Consortium (rebuildingakidney.org), the Nuclear Receptor Signaling Atlas (www.nursa.org), the Diabetic Complications Consortium (www.diacomp.org), the Mouse Metabolic Phenotyping Centers (www.mmpc.org), the Intestinal Stem Cell Consortium (iscc.coh.org), or the GenitoUrinary Development Molecular Anatomy Project (www.gudmap.org).

Additional opportunities for those who have not yet identified prototype therapeutics, require additional assistance in pre-clinical development, or are considering commercialization of products should explore the NIDDK website on Translational Research for Therapeutic Discovery and Development (www.niddk.nih.gov/research-funding/process/translational-research-therapeutic-discovery-development/Pages/default.aspx).

Applicants are also encouraged to take advantage of the resources provided by the National Center for Advancing Translational Sciences' Clinical Translational Science Awards (CTSAs) program, (www.ncats.nih.gov/ctsa) to leverage resources for therapeutic discovery in areas described in this FOA. CTSA resources include, for example, core facilities, super computer centers, biostatistics, bioinformatics, community engagement network, tissue repositories, and animal models. For more information about resources available at individual CTSAs, please see the list of CTSA Hubs (www.ncats.nih.gov/ctsa/about/hubs).

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Aaron Pawlyk
Division of Diabetes, Endocrinology, and Metabolic Diseases
6707 Democracy Boulevard, Room 7207
Bethesda, MD 20892
Telephone: 301-451-7299
Email: [email protected]

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

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

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

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

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

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

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, with the following additional instructions:

Research Strategy. Fit for the NIDDK and Intellectual Property Landscape

Applications must include a strong justification for the selection and appropriateness to the mission of the NIDDK of both the small molecule or non-viral biologic.

As part of the justification of novelty of the therapeutic, applications must also include a discussion of the relevant prior art, intellectual property, and competitive landscape.

Technique Prerequisites

Applications must include detailed descriptions of their prototype therapeutics, assays, and, when appropriate, co-development of new technologies. Assays should be presented within the context of a therapeutic lead testing flow diagram, demonstrating sufficient throughput to support testing based on their position in the flow diagram. If proposing co-development of new assays or other technologies, applicants must include a section discussing why the development of these technologies is necessary to advance therapeutic lead validation for a disease relevant to the mission of the NIDDK and provide preliminary data that the approach is feasible.

Milestones and Timeline

Applicants are required to include project performance and timeline objectives, including:

• A clear description of all interim objectives to be achieved during the course of the project and how they relate to the overall goal of extending therapeutic lead validation;
• A detailed schedule or timeline for the anticipated attainment of each milestone and the objective of extending therapeutic lead validation;
• When applicable, an explanation of how iterative rounds of therapeutic lead generation and testing will be used to assess the validity of the therapeutic lead for disease treatment throughout the project period;
• Plans for the future pre-clinical development of the resulting therapeutic agent.

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

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

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.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: 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.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

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

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

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

Important reminders:

All PD(s)/PI(s) 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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? Is there a valid scientific and therapeutic need for additional therapeutic agent discovery and development within the proposed NIDDK-relevant disease area?

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? Do the team members possess the scientific expertise to effectively pursue therapeutic lead optimization/evaluation with the goal of translating the knowledge gained to disease relevant applications?

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? Does the project pursue a target, small molecule, or biologic that is not already the subject of significant translatable efforts in the biotechnology or pharmaceutical industry towards an NIDDK-relevant disease, as described in the Purpose section of the FOA? If appropriate, does the application address the intellectual property and competitive landscapes? If co-development of a new animal model or other technology is proposed, will it address a clear need and significantly advance therapeutics discovery efforts in the field?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? Does the approach propose research that will initiate, continue, or enable the translation of basic research towards strong validation of a target, small molecules, or non-viral biologic? Have the investigators proposed realistic and achievable milestones and timeline for the proposed work? Have they included a realistic plan for future development of therapeutic agents?

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

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Does the scientific environment provide the necessary resources to effectively pursue preclinical validation of therapeutic leads with the goal of translating the knowledge gained to a disease relevant application?

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

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

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

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

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

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

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

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

Not Applicable

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

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.

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

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

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

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

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

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.
• Relevance of the therapeutic indication to the mission of the NIDDK.

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

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

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

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

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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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 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 Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Aaron C. Pawlyk, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-7299
Email:[email protected]

Elaine Sierra-Rivera, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1043
Email: [email protected]

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

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

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