Department of Health and Human Services

Participating Organization(s)
National Institutes of Health (NIH)
Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title
Early-Stage Preclinical Validation of Therapeutic Leads for Diseases of Interest to the NIDDK (R01 Clinical Trial Not Allowed)
Activity Code
R01 Research Project Grant
Announcement Type

Reissue of PAR-16-121

Related Notices
None
Funding Opportunity Announcement (FOA) Number
PAR-19-294
Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.847

Funding Opportunity Purpose

The goal of this Funding Opportunity Announcement (FOA) is to support translational research that provides strong justification for later-phase therapeutics discovery and development efforts in health-related outcomes relevant to the National Institute of Diabetes and Digestive and Kidney Diseases. This includes outcomes relevant to obesity, diabetes and related aspects of endocrinology and metabolism, digestive diseases, liver diseases, nutrition, kidney and urological diseases, and hematology. Additional information concerning programmatic areas at NIDDK is available at www.niddk.nih.gov/research-funding/research-programs/Pages/default.aspx and applicants are strongly encouraged to discuss research priorities with the Scientific Contact.

The objective of this FOA is to stimulate early-stage preclinical validation of therapeutic leads (that need not be finalized therapeutics, henceforth called "therapeutic leads") such as small molecules or non-viral biologics that are not currently a focus within the biotechnology and pharmaceutical industries. It is expected that there is significant novelty in the target, small molecule, or non-viral biologic and in how the resulting therapeutic would differentiate from existing therapies. This must be articulated clearly in the application. It is not intended to support research focused on understanding normal biology, disease processes, generating lists of putative new targets, or identifying new therapeutic uses for existing compounds.

At the end of the project period, a successful project will have provided a significant contribution to the data supporting the validity around a therapeutic such that it can advance further through other funding mechanisms, such as the small business program (https://sbir.nih.gov/niddk/index).

Posted Date

June 6, 2019

Open Date (Earliest Submission Date)
October 12, 2019
Letter of Intent Due Date(s)

Oct 12, 2019, June 14, 2020, Oct 12, 2020, June 14, 2021, and Oct 12, 2021

Application Due Date(s)

Nov 12, 2019, July 14, 2020, Nov 12, 2020, July 14, 2021, and Nov 12, 2021, by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Nov 12, 2019, July 14, 2020, Nov 12, 2020, July 14, 2021, and Nov 12, 2021, by 5:00 PM local time of applicant organization.

All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Scientific Merit Review

Feb/Mar 2020, Oct/Nov 2020, Feb/Mar 2021, Oct/Nov 2021, and Feb/Mar 2022

Advisory Council Review

May 2020, Jan 2021, May 2021, Jan 2022, and May 2022

Earliest Start Date

July 2020, Apr 2021, July 2021, Apr 2022, and July 2022

Expiration Date
November 13, 2021
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

Background

Recent significant advances in genetics, physiology, and the pathogenesis of disease coupled with technological advances 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 this, there are numerous failures of potential therapeutics for reasons related to human safety or efficacy, or the inability of a promising preclinical therapeutic to differentiate from those used in current standard clinical care. It is necessary to develop better strategies to validate and prioritize therapeutic leads based on their likelihood of success to safely improve upon current standard of clinical care.

Research Goals and Objectives

This FOA is intended to support projects that extend the 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. Submitted applications should focus on a therapeutic lead that will modulate a health-related outcome of interest to the NIDDK and improve upon current standard of clinical care. Funding priority will be given for projects that have the potential to significantly improve upon or differentiate from existing clinical care (e.g., an anti-diabetic agent that improves glycemia and protects the kidney would be a priority over one that only improves glycemia; a novel mechanism would be given priority over a heavily mined pathway). Prior to submitting an application, investigators are strongly encouraged to contact the Scientific Contact for this FOA to discuss the appropriateness and funding priority of the proposed research. 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.

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

  • Engineering of a therapeutic lead protein and its use in proof of concept studies in animal and/or human tissue-based models of disease;
  • 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;
  • 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.

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);
  • Applications that propose new therapeutic uses (i.e., repurposing for a therapeutic that is either currently approved for use in humans or that is being supported by private companies for another indication);
  • 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;
  • Mechanistic research on understanding normal biology or disease processes;
  • Projects in which the focus is medicinal chemistry or protein engineering without an integrated plan to evaluate the validity of the therapeutic for a health-related outcome within the mission of the NIDDK;
  • Applications focused primarily 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, if appropriate, 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 projects may include mechanistic studies related to evaluating efficacy and safety. If applicable, applicants should describe the necessity of mechanistic studies for informing further preclinical or clinical development of the therapeutic lead.

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 and generating preliminary evidence that they may significantly impact a disease process. (Not appropriate for this FOA and may be better suited for other programs.)

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. (Appropriate for this FOA)

Preclinical development: Activities undertaken to prepare a potential clinical candidate for an IND or BLA filing such as GMP manufacturing, extensive GLP IND-enabling toxicology, scale-up synthesis, etc. (Not appropriate for this FOA and may be better suited for other programs.)

Clinical development and 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. (Not appropriate for this FOA and may be better suited for other programs.)

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, preclinical development, or clinical development and validation. It is expected that later stage therapeutics discovery and development efforts would 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.

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 derivatives. 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, but not limited to

  • 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 tissue chips or human organoid systems) may occur alongside  benchmarking with more established assays.

Utilization of Related Resources

Applications may propose interaction with NIDDK-supported 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 Kidney Precision Medicine Project (kpmp.org), the Type 2 Diabetes Knowledge Portal (www.type2diabetesgenetics.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), or the Illuminating the Druggable Genome program (druggablegenome.net). Additional NIDDK-supported resources can be found at the NIDDK Information Network (dknet.org).

Additional opportunities for those who have not yet identified prototype therapeutics, require additional assistance in preclinical 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).

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

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIH intends to fund an estimate of 3-4 awards, corresponding to a total of $1.5 million total costs, for fiscal years 2019, 2020, and 2022. Future year amounts will depend on annual appropriations.

Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

1. Eligible Applicants

Eligible Organizations

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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

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

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.
  • 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.

Eligible Individuals (Program Director/Principal Investigator)

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

 

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)

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.

 

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:

Aaron Pawlyk, Ph.D
Email:aaron.pawlyk@nih.gov

Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed
Instructions for Application Submission
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.
SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

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

With the following additional instructions:

Facilities & Other Resources: This section should contain sufficient information to assess if the scientific environment provides the necessary resources to effectively pursue preclinical validation of therapeutic leads with the goal of translating the knowledge gained to a disease relevant application.

SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.

With the following additional instructions:

Biographical Sketch: The Personal Statement of each Biographical Sketch should indicate how the key/senior personnel's scientific expertise will be applied towards advancing therapeutic lead optimization and/or evaluation with the goal of translating the knowledge gained to disease relevant applications.

 

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

R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: The applicants should describe how the proposed research approach will initiate, continue, or enable the translation of basic research towards strong validation of a therapeutic small molecule or non-viral biologic.

Additionally, the Research Strategy must include labeled components, described below, addressing the ‘Fit for the NIDDK and Intellectual Property Landscape’ and detailing the project's proposed ‘Milestones and Timelines'. Applications lacking either of these sections will be considered incomplete.

Fit for the NIDDK, Intellectual Property, and Competitive Landscape

Applications must include a strong justification for the selection and appropriateness to the mission of the NIDDK of the therapeutic lead.This must include a discussion of the scientific and therapeutic need for the additional therapeutic agent and how the therapeutic would improve upon the existing standard of clinical care in a non-incremental manner. 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. Any significant translatable efforts in the biotechnology or pharmaceutical industry related to the therapeutic and its target (if known) must be described.

Milestones and Timeline

Applicants are required to include project performance milestone 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 after a single funding period.
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.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving NIH-defined human subjects research, clinical research, and/or 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.

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.

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, 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.

Use of Common Data Elements in NIH-funded Research
Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials
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.

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.

Overall Impact

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).

Scored Review Criteria

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 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: Is there a valid scientific and therapeutic need for additional therapeutic agent discovery and development within the proposed NIDDK-relevant disease area? Will the proposed therapeutic offer new treatment paradigms and be a significant, non-incremental advance?

 

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?

Specific to this FOA: 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?

Specific to this FOA: 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? Does the application address intellectual property and competitive landscapes? Will the proposed therapeutic significantly improve upon or differentiate from existing clinical care?

 

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 approach propose research that will initiate, continue, or enable the translation of basic research towards strong validation of a therapeutic small molecule or non-viral biologic? Have the investigators proposed realistic and achievable milestones and timeline for the proposed work? Have they included realistic plans for future pre-clinical development?

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?

 

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?

Specific to this FOA: 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?

Additional Review Criteria
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 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.

 

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.

 

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.

 

Not Applicable

 

Not Appicable

Additional Review Considerations

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

 

Not Applicable

 

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

 

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), 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 on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board.

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.

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.

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.

Cooperative Agreement Terms and Conditions of Award
Not Applicable

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.

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

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: GrantsInfo@nih.gov (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: support@grants.gov

Scientific/Research Contact(s)

Aaron C. Pawlyk, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-7299
Email:pawlykac@mail.nih.gov

Peer Review Contact(s)

Elaine Sierra-Rivera, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1043
Email:riverase@csr.nih.gov

Financial/Grants Management Contact(s)

Christina Coriz
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8848
Email:corizc@niddk.nih.gov

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

Authority and Regulations
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.


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