Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)
U.S. Food and Drug Administration  (FDA)

Components of Participating Organizations

National Center for Advancing Translational Sciences (NCATS)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title

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

Activity Code

UH3 Exploratory/Developmental Cooperative Agreement

Announcement Type

Reissue of RFA-TR-12-005

Related Notices

NOT-TR-14-001

  • June 3, 2014 - this Notice is to inform potential applicants that the National Cancer Institute (NCI) and the National Heart, Lung, and Blood Institute (NHLBI) are participating, effective immediately, in PAR-14-211. See Notice NOT-TR-14-006.
Funding Opportunity Announcement (FOA) Number

PAR-14-211

Companion Funding Opportunity

PAR-14-213 X02 Pre-application;

PAR-14-212 UH2/UH3 Phase Innovation Awards;

PAR-14-211 UH2/UH3 Phase Innovation Awards

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

93.350, 93.867, 93.866, 93.273, 93.865, 93.279, 93.173, 93.121, 93.242, 93.853, 93.103, 93.395, 93.837, 93.838, 93.839 

Funding Opportunity Purpose

The National Center for Advancing Translational Sciences (NCATS) seeks to expand the therapeutics discovery program piloted in 2012, to explore new therapeutic uses for proprietary drug candidates (Agents) across a broad range of human diseases. This innovative program allows investigators to propose new therapeutic uses for Agents from pharmaceutical company partners. A strong application will be supported by scientific evidence that modulation of the Agent’s target will have a positive impact on the disease/condition.

PAR-14-213 encourages X02 pre-applications for the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules.  The X02 pre-application is the first step in the application process for PAR-14-212, PAR-14-210, and PAR-14-211; applicants must read all of the companion FOAs.  The X02 pre-applications will be evaluated by outside experts.

Investigators whose X02 pre-applications are judged to be the most meritorious will be notified of the opportunity to submit a UH3 application under this FOA or a UH2/UH3 under PAR-14-212 or a UH2/UH3 application under PAR-14-210 in the case of a pediatric indication.

The UH3 will support milestone-driven Phase 2a trials to demonstrate that the Agent, 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 disease population.

Key Dates
Posted Date

May 12, 2014

Open Date (Earliest Submission Date)

December 16, 2014

Letter of Intent Due Date(s)

None

Application Due Date(s)

January 16, 2015, by 5:00 PM local time of applicant organization.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2015

Advisory Council Review

May 2015

Earliest Start Date

July 2015

Expiration Date

January 17, 2015

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


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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

In June 2012, NCATS issued its first Funding Opportunity Announcements (FOAs) which were for an NIH-Industry Pilot Program: Discovering New Therapeutic Uses for Existing Molecules. The pilot was designed to increase engagement and partnerships between academia and industry in drug repurposing and to enhance the success of these efforts. These objectives were met using several innovative strategies.  When the FOAs were published, information about investigational Agents (new molecular entities (NMEs) and biologics) from pharmaceutical companies was made publicly available. Also made publicly available were template collaborative research agreements (CRAs) and template confidential disclosure agreements (CDAs) that would be executed between the NIH applicant and the pharmaceutical company providing the Agent. The use of the template CDAs and CRAs in the pilot program led to rapid establishment of pharmaceutical-academic collaborations. The increased awareness and availability of these Agents to the research community resulted in submissions to NIH of almost 160 pre-applications for a wide array of diseases.    

This robust response from both the pharmaceutical industry and from the research community was a strong indicator of a high level of enthusiasm for the pilot.  Based on these indicators as well as feedback obtained through a Request for Information (RFI; http://grants.nih.gov/grants/guide/notice-files/NOT-RM-13-021.html), and surveys of awardees, the pharmaceutical companies, and NIH Components, NCATS is issuing this new round of Funding Opportunity Announcements (FOAs).

FOA

Type of research supported

Period of support (maximum)

X02

Requisite pre-application (no research supported)

N/A

UH3

Phase 2a Clinical Trial

2 years

UH2/UH3

UH2: Pre-clinical and/or Phase 1b; UH3: Phase 2a Clinical Trial

1 year for UH2 and 2 years for UH3

UH2/UH3 Pediatrics*

UH2: Pre-clinical, Phase 1a Clinical Trial, pediatric toxicology, and Phase 1b; UH3: Phase 2a Clinical Trial

2  years for UH2 and 2 years for UH3

* 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 2a trials in the pediatric population are required even though an adult patient population exists. 

Research Objectives

This funding opportunity announcement (FOA) intends to support innovative ideas from the biomedical research community for the discovery of potential therapeutic uses of those Agents in previously unexplored diseases. Proposed human trials can include: 1) use of an Agent 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 Agents are of interest.

For this FOA, Phase 1b, and Phase 2a trials are defined as follows: Phase 1b trials are defined as studies usually conducted in the target patient population to establish feasibility (e.g., target engagement, pharmacodynamics/pharmacokinetics (PD/PK), initial dosing of the Agent) prior to a Phase 2a trial. Phase 2a 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), typically 150 subjects or less for trials in adults.

UH3 objectives

The UH3 activities will include exploratory, milestone-driven Phase 2a trials designed to demonstrate that the Agent modulates the target and has the potential to yield the desired clinical outcome in the proposed disease population and assess its potential for further clinical development. 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 Agent; or the use of molecular markers of disease, pharmacogenomics, or other biomarkers as patient selection strategies. The duration of the UH3 project period is up to two years.

In cases where the Phase 2a 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 Agent for the new therapeutic use, including requisite Phase 3 clinical trials, ultimately commercializing the novel therapeutic intervention for the new disease indication whenever feasible. 

Research Areas of Interest

National Center for Advancing Translational Sciences (NCATS)

NCATS will consider co-funding projects that address a disease for which there is no or inadequate treatment and for which there is strong scientific rationale.  NCATS is particularly interested in rare diseases.  

National Eye Institute (NEI)

NEI will consider funding projects to treat eye diseases, as well as those projects aimed at interventions to preserve vision.

National Institute on Aging (NIA)

NIA will consider funding projects consistent with its mission of reducing the burden of diseases and conditions associated with aging.

National Institute of Alcohol Abuse and Alcoholism (NIAAA)

Currently, there are only a few FDA-approved drugs to treat alcohol use disorder (AUD).  Given the heterogeneity of this disorder, the modest effect size of approved medications, and the numerous targets involved with AUDs, development of new, effective medications to treat AUD is a top priority for NIAAA.  NIAAA will consider funding projects to investigate the use of existing molecules to treat AUD.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NICHD will consider funding projects with a pediatric focus, particularly pediatric rare and neglected diseases.

National Institute on Drug Abuse (NIDA)

Currently, there are no FDA-approved medications to treat substance use disorders (SUDs) involving stimulants (cocaine and methamphetamine), although there are approved medications for SUDs involving opiates.  The development of medications to treat SUDs is a top priority for NIDA.  NIDA will consider funding projects to investigate the use of existing molecules to treat SUDs involving cocaine, methamphetamine, cannabis, nicotine, or opiates.

National Institute on Deafness and Other Communication Disorders (NIDCD)

NIDCD will consider funding projects focused on communication disorders of hearing (including tinnitus), balance, taste, smell, voice, speech and language, including biomedical and behavioral problems associated with people who have these communication impairments or disorders. 

National Institute of Dental and Craniofacial Research (NIDCR)

NIDCR will consider funding projects to treat conditions affecting the oral cavity or that improve dental and craniofacial health.

National Institute of Mental Health (NIMH)

NIMH will consider funding projects that focus on the treatment and prevention of psychiatric disorders in adults and children and are consistent with the NIMH’s emphasis on the experimental therapeutic approach. Consistent with the Research Domain Criteria (RDoC), NIMH is particularly interested in testing novel interventions that focus on operationally defined, empirically-supported functional domains or symptom(s) of psychiatric disorders in subjects that share the same underlying disease processes.

National Institute of Neurologic Disease and Stroke (NINDS)

NINDS will consider funding projects consistent with its mission of reducing the burden of neurologic disease.

Food and Drug Administration (FDA)

FDA will consider co-funding projects that meet rare disease criteria per the Orphan Drug Act.

Application Process

The submission of an X02 pre-application is a necessary first step in applying for an award under this FOA or the companion FOAs. Applicants must also read the companion FOAs prior to submitting an X02 pre-application. Pre-applications submitted to PAR-14-213 will be evaluated by outside experts. X02 applicants will receive feedback on the scientific merit, technical feasibility, administration and management plans, and overall potential for impact of the science proposed in the pre-application. Investigators of  X02 pre-applications, which are identified as being highly meritorious and relevant to NIH program priorities, will be provided contact information for the appropriate pharmaceutical company based on the Agent or mechanism of action identified in their X02 pre-application. The X02 applicants and pharmaceutical company partner will jointly decide whether a UH3 application should be submitted.

X02 applicants put in contact with the pharmaceutical company partner for the Agent that was selected for studies in the X02 pre-application, are expected to execute an appropriate Confidential Disclosure Agreement (see template CDAs). Under the CDA, the applicant and pharmaceutical company partner will exchange confidential information (e.g., additional information on the Agent and studies to test the proposed new therapeutic use of the Agent), as deemed necessary, to initiate discussions. Through the CDA X02 applicants will have access to the additional information and data on the Agent, but will not have access to the Agent itself. Subsequently, it is anticipated that a Collaborative Research Agreement (CRA) between the applicant and the pharmaceutical company partner will be the vehicle through which the applicant obtains permission to work with the Agent on the research project plan for the UH3 application if an award is made. The applicant must provide the NIH with documentation of access to the Agent and associated data needed for filing an investigator-sponsored Investigational New Drug (IND) Application and for conducting the proposed clinical trial (e.g., an executed CRA).

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 Agents 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 should 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 Agent prior to submitting a UH3 application. A complete UH3 application will be contingent on the applicant’s ability to provide the NIH with documentation of access to the selected Agent and associated data needed for filing an investigator-sponsored IND in order to conduct the proposed clinical trials (e.g., an executed CRA or letter from the pharmaceutical partner).   

Agents Available for the Program

The list of Agents and non-confidential information can be found at

http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/directory2014.html 

Timeline for the Program

June 15, 2014

X02 Letters of Intent (LOIs) due

July 15, 2014

Due date for X02 pre-application

August 2014

Evaluation of pre-application by outside experts

Late September/Early October 2014

Notification of opportunity to submit a full UH3 application

January 16 2015

Due date for UH3 applications

February/March 2015

Scientific merit review for UH3 applications

May 2015

Advisory Councils for review of applications

July 2015

Earliest possible start date for awarded grants

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 award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

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

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are not limited, but need to reflect the actual needs of the proposed project.

Award Project Period

The duration of the UH3 project period may not exceed two years.

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

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:

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government 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 PAR-14-213 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 UH3 application should be submitted.

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.
  • 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 PAR-14-213 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 UH3 application should be submitted.

For these UH3 applications, the PD/PI must be the same PD/PI listed on the X02 pre-application. For UH3 applications proposing multiple PD(s)/PI(s), the contact PD/PI must 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 UH3 application.

NIH Intramural Research Program (IRP) investigators are eligible to apply for the UH3 FOA, subject to the availability of intramural funds to support the project. IRP investigators can apply as PD(s)/PI(s), as multiple PD/PIs in conjunction with extramural investigators (http://grants.nih.gov/grants/multi_pi/index.htm), or as collaborators with extramural academic or biotechnology company investigators.

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.

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

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

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

Page Limitations

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

Required and Optional Components

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

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.

Project Summary/Abstract: To ensure protection of intellectual property, applicants should discuss with the pharmaceutical company and the institutional technology transfer office the appropriate level of detail to be provided in the UH3 application title and Project Summary/Abstract since that information will be publicly available for awarded projects

Other Attachments: Attach Agent information for the Agent selected for use in the project, available at http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/directory2014.html, and title it "Agent Information".

SF424(R&R) Senior/Key Person Profile

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

The PD/PI on the UH3 application must be the same PD/PI for the X02 pre-application.

R&R Budget

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

If the applicant institution is an NIH Institute or Center, funds may not be requested for an extramural component/collaborator in the application.  

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: Define the aims of the Phase 2a clinical trial.

a. The aims should address target modulation and efficacy.

b. The clinical data resulting from the UH3 should provide sufficient evidence that the drug candidate is safe and well-tolerated for sustained administration in the proposed dose range, modulates the target/mechanism and a biomarker of PD effect, and has the potential to yield the desired clinical outcome in the disease population.

Research Strategy: Within the Research Strategy, provide the following information:

1. Background & Significance

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

b. State the biological rationale or hypothesis for the new therapeutic use of the Agent.

c. Indicate the disease, clinical population, and public health need that will be addressed by the proposed new use of the Agent.

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

2. Preliminary Studies

a. The Preliminary Studies will 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 disease pathology.

2). Data to support the selection and relevance of the Agent/mechanism of action in the new disease area (e.g., choice of assays, outcome or endpoints selected).

3). Data to support the selection of dose and exposure of the Agent based on available PD/PK biomarkers or functional pharmacological activity.

4). Information on the risk/benefit of the Agent to patients and the operational feasibility of conducting clinical trials to address the specific aims.

3. Approach

a. Describe and justify the design of the Phase 2a clinical trial to assess activity of the Agent to change the disease state in the proposed patient group.

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

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

3). Specify dose range and PD parameters used to perform dose ranging, using the company-specified route of administration and formulation (new formulations and changes in route are not allowed).

4). Discuss plans and resources available for timely filing of an IND and rapid Institutional Review Board (IRB) approval.

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

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 2a study (based on the proposed outcome measures and the appropriateness of the statistical methods).

1). The sample size and duration of the Phase 2a clinical trial should be justified for the specific disease population.

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

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.

4. 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 Agent.

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

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

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

b. Explain the proposed contribution of each of the administrative components to achieving the objectives of the program.

c. Describe relevant experience and knowledge of public-private partnerships.

d. Describe the team's experience in the methods and approaches for design and implementation of human clinical trials and readiness to test the hypothesis.

e. Describe the team's requisite competencies and experience with clinical trials recruitment and execution and ability to recruit and enroll patients in the target disease population.

5. Milestones and Timeline 

Include clearly-specified, well-defined milestones, go/no go decision points, and timelines for assessing progress.

a. The application must:

1). Assess operational feasibility and resources needed: human subjects protection approval and monitoring necessary to complete the work of the UH3 (e.g., IND, IRB approval, Data and Safety Monitoring Plan approval), access to and number of patients, patient selection criteria, availability of the Agent, and formulation.

2). Provide a clear timeline, interim milestones and go/no decision points for the clinical trial.

3) Provide enrollment rate (e.g., number of subjects meeting eligibility criteria for enrollment per month, criteria for terminating the study if minimum recruitment milestones are not met by the mid-point of the study).

4). Describe decision points for terminating the trial (e.g., safety, tolerability, patient acceptability issues). See regular reporting as specified in the Terms and Conditions.

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

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

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

6. Future Plans

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

Protection of Human Subjects: Address Human Subjects protections for any clinical research anticipated in the period of the grant, as described in the SF 424 (R&R) application instructions. Human subjects protection should be detailed for the proposed Phase 2a clinical trial. Describe in detail known information and possible contingencies regarding potential risks and benefits to participation, and plans to obtain informed consent. Include anticipated plans for data and safety monitoring commensurate with potential risks inherent in Phase 2a clinical trials.  

Inclusion of Women and Minorities, Inclusion of Children: Provide description of plans for adequate inclusion of minorities and women in the clinical sample, or justify any exclusion(s). Include a targeted/planned enrollment table for each of the planned studies involving human subjects. Provide description of plans for adequate inclusion of children in the clinical sample, or justify any exclusions. Inclusion plans should be provided separately for each stage of the award.

Letters of Support: Applicants must include a letter of support from the pharmaceutical company partner documenting: access to the Agent and associated data needed for conducting the proposed pre-clinical studies and for filing an investigator-sponsored IND for the Agent 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.).

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

For Intramural Scientists, an official letter from the Scientific Director, which indicates approval of the intramural scientist's role as PD/PI or as collaborator in the project, must be included as a letter of support in the UH2/UH3 application. The letter must specify the Scientific Director's commitment of intramural research funds to support the intramural investigator's proposed UH2/UH3 project or project component.

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

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Positive or negative data from NIH supported clinical trials should be made available to the research community through ClinicalTrials.gov, publications, or public website, consistent with achieving the goals of the Program. The applicant should address a plan and timeline for sharing clinical trial data.

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.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. 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.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

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

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff 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.

Data and Safety Monitoring

All NIH supported clinical trials, including Phase I trials, require monitoring (NIH Guidance on Data and Safety Monitoring for Phase 1 and Phase 2 Trials NOT-OD-00-038). Although a general DSMP may be appropriate for the initial grant application, NIH staff must review and approve a detailed DSMP with required supporting material prior to the start of any trial. Early discussions with NIH staff are encouraged to prevent delays. The proposed level of monitoring should be commensurate with risk. For many studies, the grantee manages data and safety monitoring. In specific cases, NIH may establish and manage independent data and safety monitoring boards (DSMBs) for trials that utilize NIH grant resources. For Phase 2a trials, this level of monitoring may be appropriate if the studies have multiple clinical sites, are blinded (masked), or employ particularly high-risk interventions or vulnerable populations. In these cases, NIH establishes a charter, appoints members and an executive secretary, provides conflict of interest vetting, and supports the activities of the DSMB. The NIH is responsible for continuing oversight even if monitoring is delegated to the grantee. All other NIH Policies related to clinical research, including trials, will also apply to the UH3 award.

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.  The intramural scientist may submit a separate request for intramural funding as described above.

If selected, NIH intramural scientists, in conjunction with their respective technology transfer representative, will need to contact the pharmaceutical company partner providing the selected Agent 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 NOT-OD-13-030.

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.

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

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? 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? Does the proposed project have the potential for influence with regard to a new therapeutic use for the Agent 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? What are the qualifications, experience, and commitment of the personnel involved in the proposed therapeutics discovery 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? 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? Although the Agent itself was not accessible to the PD/PI, what is the evidence for the biological hypothesis for the proposed new use of the Agent (its pharmacologic mechanism of action or target) and relevance of the biology to therapeutic intervention in the proposed disease? Does the evidence adequately support the hypothesis? Are procedures in place for quality control and quality assessment of the clinical study implementation? Are data management and support procedures developed sufficiently to allow tracking of clinical trial data? Have the PD(s)/PI(s) provided an operational plan for managing the necessary collaborations between and among clinical investigators and the pharmaceutical company partner? Have the PD(s)/PI(s) discussed a plan for regulatory guidance in writing and timely submission of an IND application for the clinical trials, IRB review and approval, and timely patient recruitment? Is there a plan to incorporate relevant Patient Advocacy Groups (PAGs)? If PAGs are not included, is there rationale to support their exclusion? What is the likelihood of the proposed project in meeting the goals under the compressed timelines of the FOA? Has the PD/PI provided evidence that the proposed number of eligible subjects can be recruited in the requested timeframe? Does the applicant have the ability to complete the proposed phase 2a clinical trial within the 2-year project period of the UH3?

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? 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.

Milestones and Timeline

Are appropriate, evaluative milestones clearly defined? Are the UH3 milestones feasible, well developed and quantifiable with regard to the specific aims?  Are the go/no go decision points, recruitment goals, and timelines appropriate for the Phase 2a clinical trial in the UH3?

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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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) Genome Wide Association Studies (GWAS).

Reviewers will also evaluate and comment on the plan and timeline for sharing positive or negative clinical trials data (e.g., through ClinicalTrials.gov, publications, or public website).

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.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.
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

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

Milestones and Timeline

Prior to funding an application, the Program Official will contact the applicant to discuss the proposed UH3 milestones and potential changes suggested by NIH staff or the NIH review panel. The Program Official and the applicant will negotiate and agree on a final set of approved UH3 milestones. Interim milestones in the UH3 stage will be the basis for judging progress towards and completion of the UH3 milestones.

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.

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, drafting 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; 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.
  • 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:

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 weekly project update meetings with the PD/PI.

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 for the project. 
  • 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 UH3 project for any of the following reasons: (1) inadequate progress in meeting the pre-negotiated milestones and timelines; (2) risk to subject safety; (3) slow accrual; (4) data from a futility analysis; or (5) 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.  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 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. Applicants should consider holding at least one in person meeting annually in the Washington, D.C. area to allow attendance of NIH staff.
  • 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 Phase 2 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.

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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. 

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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Christine Colvis, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone:   301-451-3903
Email: therapeuticsdiscover@mail.nih.gov

George McKie, Ph.D.
National Eye Institute (NEI)
Telephone: 301-435-8152
Email: george.mckie@nih.gov

Linda Brady, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3563
Email: lbrady@mail.nih.gov

Jill Heemskerk, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-0081
Email: heemskej@mail.nih.gov

Janet Cyr, Ph.D.
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-402-3458
Email:  cyrj@nidcd.nih.gov

Ivan Montoya M.P.H., MD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-8639
Email: imontoya@nih.gov

Larry Refolo, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-594-7576
Email: refolol@mail.nih.gov

Fertig, Joanne, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0635
Email: jfertig@mail.nih.gov

Patricia Walicke, M.D., Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: Patricia.Walicke@nih.gov

Anne Zajicek, M.D., Pharm.D.
National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6865
Email: zajiceka@mail.nih.gov

R. Dwayne Lunsford, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-2421
Email: lunsfordr@mail.nih.gov

Katherine Needleman, Ph.D.
U.S. Food and Drug Administration (FDA)
Telephone: 301-796-8664
Email: Katherine.Needleman@fda.hhs.gov

Barbara Mroczkowski, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-496-4291
Email: mroczkowskib@mail.nih.gov

John W Thomas, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: thomasj@nhlbi.nih.gov

Patricia J. Noel, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: noelp@nhlbi.nih.gov

Simhan Danthi, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-451-5170
Email: ndanthi@mail.nih.gov

FAQs:
http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/therapeutics-faq.html

For questions related to proposed new therapeutic uses of the Agents in specific disease areas, Institute or Center contacts can be found at

http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/contacts.html

Peer Review Contact(s)

Sheri Hild, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0811
Email: NCATSTDReview@mail.nih.gov

Financial/Grants Management Contact(s)

Jenelle Wiggins
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0843
Email: JWiggins@mail.nih.gov

William Darby
National Eye Institute (NEI)
Telephone: 301-435-2020
Email: darbyw@mail.nih.gov

Rebecca Claycamp
National Institute of Mental Health (NIMH)
Telephone: 301-443-2811
Email: rclaycam@mail.nih.gov

Chris Myers
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-435-0713
Email: myersc@nidcd.nih.gov

Ericka Wells
National Institute on Drug Abuse (NIDA)
Telephone: 410-254-1853
Email: wellse2@mail.nih.gov

Jillian Morris
National Institute on Aging (NIA)
Telephone: 301-496-8986
Email: morrisjil@mail.nih.gov

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@mail.nih.gov

Tijuanna DeCoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

Bryan Clark
National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: Clarkb1@mail.nih.gov

Diana Rutberg
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: dr258t@nih.gov

Garcia Nelson
National Cancer Institute (NCI)
Telephone: 240-276-5613
Email: garcian@efdb.nci.nih.gov

Kimberly Stanton
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
Email: Kimberly.stanton@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 Parts 74 and 92.

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