Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Advancing Translational Sciences (NCATS)

National Institute of Dental and Craniofacial Research (NIDCR)

Funding Opportunity Title

Limited Competition for NIH-Industry Program: Discovering Pediatric New Therapeutic Uses for Existing Molecules (UG3/UH3)

Activity Code

UG3/UH3 Exploratory/Developmental Phased Innovation Awards Cooperative Agreement  

Announcement Type

Reissue

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-TR-17-003

Companion Funding Opportunity

RFA-TR-17-001 X02 Pre-application 

RFA-TR-17-002  UG3/UH3 Phase Innovation Awards Cooperative Agreement

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

93.350, 93.121

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits applications that support testing new therapeutic uses for experimental drugs or biologics (Assets) across a broad range of human diseases unique to pediatric populations. This innovative program allows investigators to propose new therapeutic uses for Assets from pharmaceutical company partners. Strong applications will include scientific evidence that modulation of an Asset’s target will have a positive impact on the disease/condition.

An X02 pre-application is the first step in the application process for RFA-TR-17-002 and RFA-TR-17-003. X02 pre-applications will be evaluated by outside experts. Investigators whose X02 pre-applications are judged to be the most meritorious and relevant to NIH program priorities will be notified of the opportunity to submit a UG3/UH3 application under this FOA. The initial UG3 award will support the development of rigorous, pre-clinical efficacy studies and clinical trial planning activities.  If UG3 pre-clinical milestones are met, the UH3 award may be made to support clinical trials.   

Key Dates
Posted Date

February 16, 2017

Open Date (Earliest Submission Date)

August 15, 2017

Letter of Intent Due Date(s)

August 15, 2017

Application Due Date(s)

September 15, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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.

No Late applications will be accepted for this FOA.

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

December, 2017

Advisory Council Review

January 2018

Earliest Start Date

February 2018

Expiration Date

September 16, 2017

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 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.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners.

  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. Go to Grants.gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.gov; and track your application in eRA Commons.
Learn more about the various submission options.

Table of Contents

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

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) solicits applications that support testing new therapeutic uses for experimental drugs or biologics (Assets) across a broad range of human diseases unique to pediatric populations. This innovative program allows investigators to propose new therapeutic uses for Assets from pharmaceutical company partners. Strong applications will include scientific evidence that modulation of an Asset’s target will have a positive impact on the disease/condition. The initial UG3 award will support the development of rigorous, pre-clinical efficacy studies and clinical trial planning activities.  If UG3 pre-clinical milestones are met, the UH3 award may be made to support Phase I and II clinical trials.

An X02 pre-application is the first step in the application process for RFA-TR-17-002 and RFA-TR-17-003. X02 pre-applications will be evaluated by outside experts. Investigators whose X02 pre-applications are judged to be the most meritorious and relevant to NIH program priorities will be notified of the opportunity to submit an UG3/UH3 application under this FOA.

Background

Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) is a collaborative program designed to develop partnerships between pharmaceutical companies and the biomedical research community to advance therapeutics development. This innovative program matches researchers with a selection of pharmaceutical industry Assets to test ideas for new therapeutic uses, of those Assets, with the ultimate goal of identifying promising new treatments for patients. The program was designed to enable efficient 3-way drug repurposing partnerships between academic, government, and pharmaceutical partners. Strategies used to accomplish this include posting limited confidential information about investigational Assets [new molecular entities (NMEs) and biologics] offered by pharmaceutical companies to a public website. This facilitates crowdsourcing of ideas for new therapeutic uses from academic medical centers or companies in the form of grant applications to NCATS. The program has shortened the time needed to establish collaborations to 3 to 4 months (from the typical 9 months to a year), by publicly posting template collaborative research agreements (CRAs) and template confidential disclosure agreements (CDAs) that are executed between the applicant institution and the pharmaceutical company that provides the Asset for testing a new therapeutic use.

Research Objectives and Scope

This funding opportunity announcement (FOA) intends to support the testing of innovative ideas for the discovery of new therapeutic uses of existing Assets in previously unexplored diseases unique to pediatric populations. In general, pediatric populations to be considered for this FOA refer to disease populations for which there is no adult equivalent and therefore, there is no adult population in which the drug could be tested prior to testing in children. However, trials in pediatric or juvenile populations for indications that also have an adult population (e.g., type 2 diabetes, autism, osteoarthritis) may be considered if there is a strong scientific rationale that justifies why Phase II trials in the pediatric population are required even though an adult patient population exists (e.g., the target in the pediatric population may differ from that in the adult, or treatment of children may reduce progression or severity of the disease). Assets pharmaceutical companies will consider for use in pediatric populations are listed in the Table of Assets for Pediatric Indications. Applicants need to refer to the "Additional Characteristics" row of the more detailed Asset information chart for the Asset of interest to determine the type(s) of pediatric diseases the pharmaceutical company will consider (e.g., only trials in pediatric populations for which there is no adult population; or trials for diseases/conditions that have a pediatric and adult population, if the trials in a pediatric population are scientifically justified). Applicants exploring therapies for diseases that occur in both children and adults should consider applying to the companion FOA focusing on adult populations RFA-TR-17-002.

Some of the compounds in the Table of Assets will be more amenable to exploration/use in pediatric populations than others based on the Biopharmaceutical Classification System (BCS), adult safety data, expected palatability issues, bioavailability and other criteria. A pediatric oral formulation will need to be an 1) oral solution/suspension, which is recommended for children ages 6 to 11, or 2) a small tablet/capsule, which should be considered for ages 12 to 18 years. An extemporaneous formulation of an Asset that could be prepared immediately prior to dosing is another option. Those Assets that have the potential to be used in a pediatric disease are indicated in the Table of Assets for Pediatric Indications.

This FOA is for a Feasibility/Implementation Cooperative Agreement (UG3/UH3) that allows two years of support in the UG3 feasibility stage (compared to the companion FOA RFA-TR-17-002 for adult indications that allows one year). The extra year of support [for a total of two years of support for the UG3 (for pediatric indications only)] is for required juvenile toxicity testing. Proposed human trials can include: 1) use of an Asset as a stand-alone intervention, or 2) as an adjunctive intervention with existing standard of care (if there is no evidence of drug-drug interactions with the proposed standard of care treatment). Strategies to inform the selection of patients for proposed new uses of the Assets are of interest.

For this FOA, Phase I trials are defined as initial studies in healthy adult volunteer subjects or the pediatric rare disease subjects; or other initial studies (using the proposed pediatric formulation) to determine the metabolic and pharmacological actions and the side effects (including those associated with increasing drug doses, or drug-drug interactions in cases where the assets will be tested as adjunctive treatment), as required by the FDA. A Phase I pediatric trial includes studies conducted in the target pediatric patient population to establish feasibility [e.g., target engagement, pharmacokinetic/pharmacodynamic (PK/PD), initial dosing of the Asset] prior to a Phase II trial. Phase II clinical trials provide data on the relationship of dosing and response for the particular intended use (including trials on the impact of dose ranging on safety, biomarkers, and proof of concept), in a small number of the targeted pediatric-patient population. In addition to clinical benefit, Phase II trials also include assessments of safety, tolerability, and PK/PD response of the Asset.

Proposed human trials can include: 1) use of an Asset as a stand-alone intervention, or 2) as an adjunctive intervention with existing standard of care (if there is no evidence of drug-drug interactions with the proposed standard of care treatment). Strategies to inform the selection of patients for proposed new uses of the Assets are of interest.

FDA's Guidance on Nonclinical Safety Evaluation of Pediatric Drug Products should be considered in designing pre-clinical toxicity studies (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079247.pdf).

UH3 implementation objectives

The duration of the UH3 project period is up to three years and will begin after the UG3 milestones and feasibility requirements are met. NIH approval for transition of the project to the UH3 stage will be contingent on reaching the UG3 milestones and feasibility requirements specified in the Notice of Award, and NIH receipt of clinical trial documents: clinical trial protocol, consent forms, detailed data and safety monitoring plan, data quality management plan, etc.

UH3 implementation objectives (Phase I clinical trial)

Phase I clinical trials using the selected Asset should be designed to accomplish the following: identify a safe dose range, drug exposure at the target site in the pediatric patient group if possible, inform patient selection criteria, and evaluate safety, tolerability, and side effects prior to conducting a Phase II clinical trial in a larger population. Investigators should consider the use of pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers to assess the selection of doses and exposure of the Asset at the target site of action, binding at the target, and expression of functional pharmacological activity of the Asset at the target site of action.

Transition from the Phase I to Phase II clinical trial is dependent on meeting Phase I milestones, listed in the Notice of Grant Award. Progress from the dose-finding safety and tolerability clinical trial to the Phase II efficacy signal trial is generally assessed at the transition from year 3 to year 4 of the award.

UH3 implementation objectives (Phase II clinical trial)

Phase II clinical trial activities will include exploratory, milestone-driven studies that are designed to detect a preliminary signal of efficacy in the proposed pediatric disease population to inform a decision on progressing to a larger trial. In cases where the Phase II clinical trials are successful, it is anticipated that the pharmaceutical company partner will have first right of refusal to pursue further clinical development of the Asset for the new therapeutic use. This includes requisite Phase III clinical trials that are needed to commercialize the novel therapeutic intervention for the new disease indication, whenever feasible.

The inclusion of biomarkers in the design of the study is encouraged, when appropriate: e.g., the inclusion of PK/PD biomarkers to assess target engagement, exposure and functional pharmacological activity of the Asset; or the use of molecular markers of disease, pharmacogenomics, or other biomarkers as patient selection strategies. The duration of the Phase II clinical trial is up to two years and is expected to begin as soon as the UH3 Phase I trial milestones and feasibility requirements are met. NIH approval for transition of the project to the UH3 Phase II clinical trial will be contingent on reaching the milestones and feasibility requirements specified in the Notice of Award for successful completion of the work proposed in the Phase II clinical trial, and NIH review of updated IND information, a human subjects protection plan, and a data and safety monitoring plan. In cases where the Phase II clinical trials are successful, it is anticipated that the pharmaceutical company partner will have first right of refusal to pursue further clinical development of the Asset for the new therapeutic use, including requisite Phase III clinical trials, ultimately commercializing the novel therapeutic intervention for the new disease indication whenever feasible.

Partnership Information

A key aspect of this FOA is the formation of collaborative partnerships between the biomedical research community and industry partners. NCATS has executed a Memorandum of Understanding (MOU) with each of the pharmaceutical company partners to provide a framework under which specific proprietary Assets will be provided by these partners to the program awardees. Template agreements have been developed for this program: Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) between the pharmaceutical company partner and the applicant. These template agreements have been developed to streamline interactions among the parties for the Program, and it is anticipated that applicants will use the agreements. Investigators must work with their institutional technology transfer or sponsored research office to finalize the terms and conditions of the CDA and CRA with the pharmaceutical company partner for the selected Asset, prior to submitting a UG3/UH3 application.

This initiative invites ideas for new therapeutic uses of existing molecules (Assets) from pharmaceutical company partners.  Through this program, applicants will not have access to the Assets unless an award is made. However, applicants have been provided information on the Asset through a CDA with the pharmaceutical partner.

Assets Available for the Program

The list of Assets and non-confidential information can be found at https://ncats.nih.gov/ntu/Assets/current

The following will be considered non-responsive to this FOA and will not be reviewed:

  • Applications that propose to test a drug or biologic that is not on the list of Assets for the current funding opportunity.

UG3/UH3 Phase Innovation Awards 

Applicants must plan for both a UG3 and UH3 phase in their application.  The UG3 phase must include milestone-driven pre-clinical work to determine if a clinical trial is justified.  Projects should have clear, testable hypotheses; and the research plan should use quantifiable measures for making a go/no-go decision to progress to clinical trials. Support for the UG3 may be requested for one to two years. UG3 projects that have met the scientific milestones and feasibility requirements will be eligible for rapid transition to the UH3, after NIH administrative review.  All milestones for the project will be negotiated with NIH and finalized before an award is made. The UH3 can be used for clinical trials using the selected company Asset in its existing formulation/route of administration to identify the dose or exposure of the Asset in the proposed pediatric patient group, and inform patient selection.  The project period for Phase I clinical studies is up to one year. The UH3 Phase II clinical trial is for milestone-driven trials to demonstrate that the Asset, made available for this program by the pharmaceutical partners, modulates the target and has the potential to yield the desired clinical outcome in the proposed patient population. The project period for Phase II clinical trials is up to two years.  The total project period for the UH3 may not exceed a total of three years.

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

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after an award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

New

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

Funds Available and Anticipated Number of Awards

NCATS intends to commit $6,000,000 in FY 2018 to fund 6-10 UG3/UH3 awards in response to this FOA. The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets need to reflect the actual needs of the proposed project but must not exceed $300,000 in direct costs for each year of the UG3 phase and $500,000 (direct costs) for each year of the UH3 phase.

Award Project Period

The total duration of the UG3/UH3 project period must not exceed five years. The duration of the UG3 project period is anticipated to vary in time based on the needs of the project before transitioning to a clinical trial in the UH3 stage. The UG3 project period is limited to one two years, but it may be completed sooner if the project does not require a full year the full period for the proposed UG3 studies. Applications requesting support only for document preparation during the UG3 are expected to request less than one year of support.   Funding of the UH3 award will be determined by successful completion of UG3 scientific milestones as determined by the NIH. Subsequent years of funding will be contingent on satisfactory progress on negotiated milestones.

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.

Section III. Eligibility Information
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:

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government including NIH Intramural Research Program
  • 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

This FOA is a limited competition for applicants whose X02 pre-applications submitted in response to RFA-TR-17-001 were identified as being meritorious and relevant to NIH program priorities. 

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) (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.
  • o    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.

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.

This FOA is a limited competition for applicants whose X02 pre-applications submitted in response to RFA-TR-17-001  were identified as being highly meritorious and relevant to NIH program priorities; X02 applicants will have contacted the appropriate pharmaceutical company to exchange data under a CDA and both parties will have decided that a UG3/UH3 application should be submitted.

It is strongly encouraged for UG3 applications/, the PD/PI not be changed from that listed on the X02 pre-application. For UG3/UH3 applications proposing multiple PD(s)/PI(s), it is strongly encouraged the contact PD/PI be the same PD/PI listed as the contact on the X02 pre-application. The contact PD/PI is strongly encouraged to continue the multiple PD(s)/PI(s) leadership identified in the X02 pre-application, if notified of the opportunity to submit a UG3/UH3 application.

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

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

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

Buttons to access the online ASSIST system or to download application forms 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 Research (R) 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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Carol Lambert, Ph.D.
Telephone: 301-435-0814
Fax: 301-480-3660
Email: Lambert@mail.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.

SF424(R&R) Senior/Key Person Profile

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

Describe institutional and/or project personnel experience with FDA regulatory processes.

It will be important for the PD/PI to describe experience in meeting milestones.

Describe relevant experience and knowledge of public-private partnerships.

It is strongly encouraged that the PD/PI on the UG3/UH3 application be the same as the individual named on the X02 pre-application.

R&R Budget

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: 

Specific Aims: UG3 should include Aims delineated for the (pre-clinical, pediatric toxicology, and clinical trial planning) and UH3 (Phase I and Phase II clinical trial):

1. UG3: Pre-clinical, pediatric toxicology, and clinical trial planning

a. Juvenile animal studies to assess the potential drug toxicity in one or more species.

b. Milestone-driven pre-clinical studies for making a go/no-go decision to progress to clinical trials.

c. Document preparation and approvals (clinical trial protocol, manual of operations, consent forms, IND, detailed data and safety monitoring plan, data quality management plan, etc.).

2. UH3 (Phase I clinical trial) can be used for clinical trials using the selected company Asset in a formulation/route of administration appropriate for the pediatric patient population to identify the dose or exposure of the Asset in the proposed patient group, and to inform patient selection. 

a. Define the aims of the Phase I dosing, safety and tolerability clinical trial, if such a trial is proposed.

3. UH3 (Phase II trial)

a. Define the aims of the Phase II preliminary signal of efficacy clinical trial.

1) The aims should demonstrate that the Asset, made available for the program by the pharmaceutical partners modulates the target and has potential to yield the desired clinical outcome/effectiveness in the pediatric population. 

Research Strategy: Provide the following information for the UG3 and UH3 segments.

1. Background & Significance (Overall)

a. Identify the Asset, its known pharmacologic mechanism of action or target, and route of administration.

b. State the biological rationale or hypothesis for the therapeutic potential of modulating the Asset’s target or mechanism of action.

c. Indicate the disease that is unique to the pediatric population, clinical population, and public health need that will be addressed by the proposed new use of the Asset. If the disease/condition exists in both children and adults, include strong scientific justification for testing the Asset in a pediatric patient population instead of testing in an adult patient population (e.g., the target in the pediatric population may differ from that in the adult or treatment of children may reduce progression or severity of the disease).

d. Address the global burden of disease, which patients will benefit, how they will benefit, how use of the Asset will be superior to current therapy options, and potential public health impact.

2. Preliminary Studies

a. Include Preliminary Studies that contain, but are not limited to, data and information that validate the feasibility of conducting studies to address the specific aims.

1). Evidence that the target or specific pathway is involved in the pediatric disease pathology.

2). If pre-clinical studies are proposed, data to support the selection and relevance of the proposed models to assess the efficacy of the Asset in the new pediatric disease area (e.g., choice of assays, models, species, outcome or endpoints selected).

3). Any additional relevant information on the Asset (e.g., availability of pharmacokinetics (PK) and pharmacodynamics (PD) markers, any exclusions or restrictions in the Asset's use) supporting dose and dose schedule for the Asset in the proposed new pediatric disease area.

3. UG3 Approach

UG3: Pre-clinical, pediatric toxicology, and clinical trial planning

a. Provide an overall plan to assess the validity of the biological hypothesis for use of the Asset in the new disease area.

1). Describe and justify the selection of the approach(es) to demonstrate Asset activity (e.g., pre-clinical disease models, disease assays, or patient-derived samples).

2). Consider the duration of studies, based on safety data available for the Asset, and whether the new use of the Asset is for treatment of an acute or chronic disease.  Provide/describe juvenile toxicity data results, if available. Describe proposed pre-clinical juvenile toxicity studies to support clinical trials in children, if these have not been completed. Investigators should consider FDA's Guidance on Nonclinical Safety Evaluation of Pediatric Drug Products in designing pre-clinical toxicity studies (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079247.pdf).

3). Specify dose range of the Asset and proposed route of administration. Discuss any known or expected issues with oral formulations (solubility/permeability, taste/bitterness).

4). Describe the approach and personnel resources available for timely filing of an IND and rapid Institutional Review Board (IRB) approval.

5). Applicants are strongly encouraged to consider requesting a pre-IND meeting with FDA (Type B meeting) prior to submitting their UG3/UH3 application. Guidance on FDA meetings is located at this link: http://www.fda.gov/downloads/Drugs/Guidances/ucm153222.pdf.  

6). Pre-clinical animal safety studies should be tied to a go/no go decision to test the Asset in the proposed pediatric-patient group.

4. UG3 Milestones and Timeline:

The application must include clearly-specified, well-defined milestones, go/no go decision points, and timelines for assessing progress in both the UG3 and UH3 stages (including specific milestones and timeline for progressing from the UG3 to the UH3 Phase I clinical trial and from the UH3 Phase I to the UH3 Phase II clinical trial. Milestones and the timeline for each stage must be provided in a separate heading at the end of the Approach section for each UG3 and UH3 stage.

UG3 Milestones and criteria for UG3/UH3 transition must:

a. Identify and justify the scientific milestones, go/no go decisions, and the timeline to advance studies of the Asset to the UH3 Phase I clinical trial.

1) Discuss how data generated in the UG3 studies will be assessed to determine the risk/benefit of the Asset to patients: safety, tolerability, bioavailability, PK/PD (duration of action, relationship between dose/exposure and PD).

2) Indicate plans and timing for submission of clinical trial protocol, consent forms, detailed data and safety monitoring plan, and data quality management plan for review by NIH prior to the start of the UH3 Phase I clinical trial. 

5. UH3 Approach

UH3 Phase I clinical trial          

a. Provide a plan for Phase I safety studies in healthy volunteers and to determine appropriate dosing for the proposed pediatric-patient group.

1). Describe the design to assess the safety, dosing, and tolerability including palatability of the Asset (if oral) in the proposed pediatric-patient population.

Identify the inclusion of any clinical endpoints or outcome measures.

Identify the length of the study (dosing schedule and time to obtain data endpoints), number of subjects, plans for patient recruitment, clinical monitoring and oversight, and data management.

2). Describe the use of PK and PD biomarkers, when available, to assess: dose and exposure of the Asset at the target site of action; binding at the target; and expression of functional pharmacological activity of the Asset at the target site of action.

3). Identify the inclusion of any clinical endpoints or outcome measures.

4). Identify the length of the study (dosing schedule and time to obtain data endpoints), number of subjects, plans for patient recruitment, clinical monitoring and oversight, and data management.

5). Provide an estimate for the amount of Asset needed and the formulation.

6.) Describe plans for clinical data management.

UH3 (Phase II clinical trial)

a. Provide an overall plan for the preliminary signal of efficacy Phase II clinical trial.

1). Specify the duration of studies, based on safety data available for the Asset, and whether the new use of the Asset is for treatment of an acute or chronic disease.

2). Specify dose range, PD parameters used to perform dose ranging, route of administration and dosage form, and amount of Asset needed.

b. Define the patient selection strategy.

1). Describe a plan for the involvement of Patient Advocacy Groups (PAGs) in the project. If PAGs are not included, provide a rationale for their exclusion.

2). Consider the use of molecular markers of disease, pharmacogenomics, or other biomarkers, when applicable.

c. Define the primary end points, and justify the number of patients chosen for the Phase II study (based on the proposed outcome measures and the appropriateness of the statistical methods).

1). The sample size and duration of the Phase II clinical trials should be justified for the specific pediatric disease population.

2). Discuss alternative statistical methods to show efficacy in Phase II clinical trials with small sample sizes.

3). Provide evidence that the proposed number of eligible subjects can be recruited in the requested timeframe.

4). Provide assurance that the proposed study can be completed within its budget and within the time limits stated in this FOA.

5.) Describe plans for clinical data management.

d. Specify dose range, PD parameters used to perform dose ranging, route of administration (new formulations and changes in route are not allowed), and amount of Asset needed.

6. Administration and Management

a. Provide an operational plan for managing the pre-clinical studies and clinical trials necessary to fully develop a new use for the Asset.

1). Explain the proposed contribution of each of the key participants in achieving the objectives of the project. 

2). Describe how the team's collective experience in the methods and approaches for design and implementation of clinical trials and readiness to test the hypothesis will provide synergy that promotes successful completion of the project.

3) Describe how the team's collective requisite competencies and experience with clinical trials recruitment and execution and ability to recruit and enroll patients in the target disease population will provide synergy that promotes successful completion of the project.

4) Describe the experience of the project manager and study coordinator(s).

7. UH3 (Phase I and Phase II clinical trial) Milestones and Timeline

The application must include clearly-specified, well-defined milestones, go/no go decision points, and timelines for assessing progress in both the UG3 and UH3 stages, including specific milestones and timeline for progressing from the UG3 stage to the UH3 Phase I clinical trial. Include also milestones and timeline for progress between the UH3 Phase I clinical trial (when applicable) and Phase II clinical trial. Milestones and the timeline for each stage must be provided in a separate heading at the end of the Approach section for each UG3 and UH3 stage.

The UH3 milestones must:

a. Provide a clear timeline, interim milestones, and go/no go decision points for the clinical trial, including decision points for proceeding from a Phase I dosing and tolerability trial to a Phase II efficacy signal clinical trial, if a dosing trial is proposed.

1). Enrollment rate (e.g., number of subjects meeting eligibility criteria for enrollment per month, criteria for conducting a futility analysis if minimum recruitment milestones are not met by the mid-point of the study).

2). Decision points for terminating the trial (e.g., safety, tolerability, patient acceptability issues), including palatability and the ability to swallow the dosage form).

3). See regular reporting as specified in the Terms and Conditions.

b. Identify any impediments that could require an addendum to the research strategy, milestones, or timeline with a discussion of alternative approaches.

c. Provide detailed quantitative criteria by which milestone achievement will be assessed.

d. Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.

8. Future Plans

Describe the commercial potential of the Asset as a development candidate and potential challenges for commercialization of the Asset for the new disease indication.

Data Safety Monitoring Plan:

NCATS is committed to supporting high quality clinical trials and will work with investigators to establish a monitoring plan that is tailored to the risk and complexity of the study. Early discussions with NIH staff are encouraged to prevent delays.

Letters of Support:

If multiple institutions are involved in an application, a letter of support must be included from each institution.

Applicants must include a letter of support from the pharmaceutical company partner documenting: access to the Asset and associated data needed for conducting the proposed pre-clinical studies and for filing an investigator-sponsored IND for the Asset to conduct the proposed clinical trials (e.g., a letter indicating that a CRA has been executed, and the PD/PI has the right to cross-reference specific sections of the pharmaceutical company partner's IND/Drug Master File, etc.).

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. Intramural Scientists should include an official letter from the Scientific Director, which indicates approval of the intramural scientist's role as PD/PI or as collaborator in the UG3/UH3 application. The letter must specify the Scientific Director's commitment of intramural research funds to support the intramural investigator's proposed UG3/UH3 project or project component.  Applications must include a letter from the pharmaceutical partner documenting access to the selected Asset and associated data needed for conducting the proposed pre-clinical studies and for filing an investigator-sponsored IND in order to conduct the proposed clinical trials.  Applications lacking this letter will not progress to review.

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.

PHS Inclusion Enrollment Report

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

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 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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.   As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses.  Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. 

If selected, appropriate funding will be provided by the NIH Intramural Program.  NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA.  Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights. 

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. 

If selected, NIH intramural scientists, in conjunction with their respective technology transfer representative, will need to contact the pharmaceutical company partner providing the selected Asset made available through this FOA to: execute a CDA to exchange confidential information, and negotiate a PHS Cooperative Research and Development Agreement (CRADA), Clinical Trials CRADA, or other similar type of agreement, to incorporate, as appropriate, the terms of the CRA.      

Post Submission Materials

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

Section V. Application Review Information
1. Criteria

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.

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.

Significance

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?

Specific to this FOA: Does the proposed project have the potential for influence with regard to a new therapeutic use for the Asset in a disease or disorder for which there is no current treatment or clinical outcome, or for which the current standard of care has considerable disadvantages or very limited utility? Is there a strong biological rationale for the indicated therapeutic use?    

Investigator(s)

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

Specific to this FOA: What are the qualifications, experience, and commitment of the personnel involved in the proposed new therapeutic uses project? Do the PD(s)/PI(s) have the scientific and organizational vision and experience to serve effectively as the Director(s) of the project? Is there evidence of sufficient management capabilities that include fiscal administration, personnel management, planning, and budgeting? Does the investigative team have the requisite competencies and experience with drug development, clinical trials planning, recruitment and execution? Does the investigative team have an experienced individual/office/organization to effectively manage regulatory aspects of the project? Do the PD(s)/PI(s) demonstrate relevant experience and knowledge of the public-private partnerships?     

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators 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 Do the milestones clearly-specify and well-defined the go/no go decision points, and timelines for assessing progress in both the UG3 and UH3 stages (including specific milestones and timeline for progressing from the UG3 to the UH3 Phase I clinical trial)?

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?  

Environment

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

Specific to this FOA: Are facilities adequate to implement the goals of the program, and for the overall functions of the project, including regulatory submissions, rapid IRB approval, and safety monitoring? Is there evidence for institutional commitment to the program, including provision of space, and other measures of institutional commitment? Are the research environment and resources, including equipment and facilities, adequate? Does the scientific environment indicate the potential for a multi-disciplinary approach involving teams of investigators? Is a team in place to rapidly implement the proposed studies?    

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.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

When the proposed project involves 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.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned 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 NCATS Advisory Council. The following will be considered in making funding decisions:

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

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

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

Section VI. Award Administration Information
1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

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

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

  • Determining the experimental research approaches, designing protocols, setting project milestones and go/no go decision points, and conducting the project within the guidelines of the FOA.
  • Submitting an investigator-sponsored IND, assuming responsibility for the development, assembly, and submission of all required regulatory documents, and providing all required information to NIH staff. This includes but is not limited to all communications with the Food and Drug Administration (FDA)/or other regulatory authority and the IRB.
  • Complying with all federal regulations and NIH policies, including those related to clinical research and clinical trials. Adhering to NIH requirements for clinical trial monitoring, including oversight by an independent NIH Data and Safety Monitoring Board (DSMB) if required by NIH.
  • Ensuring the timely submission of the clinical trial protocol, consent form, and periodic reports for the project to the NIH, as required.
  • Ensuring timely submission of all information and documents required by NIH, for oversight of the project and data and safety monitoring.
  • Submitting required documents, including adverse events or unanticipated problems, to the FDA or Office of Human Research Protections (OHRP) in a timely manner as required by regulation, and submitting these reports to NIH staff at the time of submission to the appropriate agency.
  • Inviting external scientist(s) to serve as advisors on the Steering Committee as needed, in consultation with the NIH Program Official, NIH Project Scientist, and pharmaceutical company partner.
  • The PD(s)/PI(s) will chair the Steering Committee, organize and circulate a written agenda in advance of conference calls and meetings, and prepare and circulate minutes that delineate decisions and action items resulting from the calls or meetings.
  • Adhering to Steering Committee policies and accepting the participation and assistance of NIH staff in accordance with the guidelines described in the NIH staff responsibilities in the Terms and Conditions of Award.
  • Providing periodic reports to the Steering Committee summarizing: the progress of the project in the UG3 and UH3 stages; obstacles encountered and solutions; monthly recruitment updates; and quarterly progress on milestones or milestone updates. The reports should be provided in a format decided upon by the Steering Committee.
  • Providing an interim report, due 60 days prior to completion of the UG3 milestones to the NIH, as specified in the Notice of Award.
  • Retaining custody of and having primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies, consistent with the terms of the CRA.
  • NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
  • Addressing all study design, operational and logistical issues, and safety, regulatory, ethical, and conflict of interest concerns raised by NCATS staff.
  • Complying with the clinical terms of award as articulated in the Notice of Award (NoA), such that no funds may be drawn down from the payment management system and no obligations may be made against federal funds for any research involving human subjects until the Program Official notifies the awardee that the identified issues have been resolved and a revised NoA is received.

The Project Scientists will:

  • Have substantial scientific/programmatic involvement during conduct of this cooperative agreement, through technical assistance, advice, and coordination above and beyond normal program stewardship of grants.
  • Coordinate with the awardees in monitoring issues relating to: design of the activities, recruitment, adherence to protocols, adjustment of study protocols, and management and technical performance.
  • Participate in all Steering Committee activities, including conference calls, subcommittees and special committees as a voting member; however, NIH voting membership will not exceed one-third of the total committee membership.
  • Participate in the review of clinical research protocols and clinical monitoring plans, and depending on their level of complexity and risk, recommend further review by the NIH DSMB or another monitoring body.
  • Participate in project update meetings with the PD/PI.
  • Request that the awardee provide the following documents for Program information and assessment prior to any subject accrual or enrollment:
  • IRB-approved clinical trial protocol conforming to Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance (ICH GCP E6), identified by protocol title, version number and date, and including details of study design, proposed interventions, subject eligibility criteria and plans for assessing, managing and reporting adverse events and unanticipated problems.
  • Documentation of IRB approval
  • IRB approved consent form, identified by version number, date or both
  • Plans for data and safety monitoring
  • Appropriate clinical trial participant risk information (the most current version of the Investigator’s Brochure).
  • Communication plan, including schedule of calls and reports to keep NIH appraised of study progress.
  • Provide comments to the awardee within three weeks of receipt of the above package of information.
  • NCATS staff comments will be forwarded to the awardee within three weeks of receipt of the above package of information.

The Program Official will:

  • Be responsible for the normal scientific and programmatic stewardship of the award.
  • Participate in all Steering Committee meetings and conference calls.
  • Monitor recruitment status of the trial on an ongoing basis.
  • Monitor performance through consideration of quarterly meetings of the Steering Committee and annual reports, site visits, and compliance with NIH procedures.
  • Approve modifications to the research plan and/or study protocol(s), in consultation with the Steering Committee, based on emerging data and/or other issues that impact progress of the project.
  • Determine if the awardee has met/achieved milestones throughout the UG3 and/or UH3 stages of the project.
  • Determine if the awardee has met the milestones and feasibility requirements for transition of the project from the UG3 to the UH3 stage.
  • Reserve the right to obtain periodic external peer review and recommend reviewers for an assessment of progress and achievement of milestones.
  • Ensure timely registration of Phase I and Phase II trials in ClinicalTrials.gov.
  • Reserve the right to terminate or curtail a UG3 or UH3 project for any of the following reasons: (1) inadequate progress in meeting the pre-negotiated milestones and timelines; (2) failure to meet the go/no go milestone(s) for transition from the UG3 to UH3; (3) risk(s) to subject’s safety; (4) slow accrual; (5) data from a futility analysis; or (6) failure to comply with the Terms and Conditions of Award.

Areas of Joint Responsibility include:

Steering Committee:

Each awardee's project will have a Steering Committee. The Steering Committee will serve as the operational governing board for each awardee’s project. The Steering Committee will include: the PD(s)/PI(s), key personnel, the pharmaceutical company collaborator or consultant as an ex officio member, the NIH Project Scientist (voting), the NIH Program Official (ex officio), and external scientist(s).

The Steering Committee will:

  • Participate in monitoring scientific progress of the UG3 and UH3 research project plan, assessing recruitment and progress of the go/no go milestones.
  • Convene quarterly meetings (in person or by video or audio teleconference) to monitor progress on the research project plan and to address issues or activities that impact the project.
  • Hold teleconferences to address operational issues on a monthly basis, or as dictated by the needs of the study.
  • Establish workgroups for specific tasks as the Steering Committee deems appropriate. The workgroups will make recommendations to the Steering Committee.
  • Ensure timely publication of abstracts and scientific articles to make results of projects and inventions available, including negative data regarding new therapeutic uses.
  • Ensure timely submission of Phase I and Phase II data to ClinicalTrials.gov.
  • Participate in monitoring of intellectual property arising from the project.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16. following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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 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.

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

Scientific/Research Contact(s)

Bobbie Ann Austin, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0824
Email: NewTherapeuticUses@mail.nih.gov

R. Dwayne Lunsford, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4635
Em ail: lunsfordr@nidcr.nih.gov

FAQs:
http://ncats.nih.gov/ntu/funding/TR17001-3-faq

Peer Review Contact(s)

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-3660
Email: Lambert@mail.nih.gov

Financial/Grants Management Contact(s)

Julia Shriner
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-0853
Email: julia.shriner@nih.gov

Diana Rutberg
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Section VIII. Other Information

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

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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