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)

Funding Opportunity Title
Drug Development Collaboratory (UG3/UH3 Clinical Trial Required)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type


Related Notices
  • NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
  • October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
  • September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
  • August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169
  • August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
  • April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity


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


Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support intramural-extramural collaborations on late-stage translational science projects between NCATS Therapeutic Development Branch (TDB) and extramural researchers, for therapeutic development of small molecules, biologics, or gene therapies. The UG3 phase will provide support for late stage pre-clinical work and clinical trial planning that is conducted at applicant institutions. The goal of any collaboration with TDB is to enable an IND application by the end of the UG3 phase. If UG3 milestones are met and an IND is cleared, support may be provided for an early stage clinical trials in the UH3 phase that will be conducted at the applicant institutions.

Key Dates

Posted Date
September 18, 2020
Open Date (Earliest Submission Date)
January 09, 2021
Letter of Intent Due Date(s)

January 9, 2021

Application Due Date(s)

February 9, 2021; June 9, 2021; February 9, 2022; June 9, 2022; February 9, 2023; June 9, 2023


All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

June 2021, November 2021, June 2022, November 2022, June 2023, November 2023

Advisory Council Review

October 2021, January 2022, October 2022, January 2023, October 2023, January 2024

Earliest Start Date

January 2022

Expiration Date
June 10, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

  3. Use Workspace to prepare and submit your application and eRA Commons to track your application.

  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description


The National Center for Advancing Translational Sciences (NCATS) was established to transform the translational science process so that new treatments and cures for disease can be delivered to patients faster. The Drug Development Collaboratory is designed to enhance latent synergies across NCATS’ laboratories (intramural) and applicant institutions (extramural) programs to build a more comprehensive therapeutic development path than either arm of NCATS can provide alone. It represents a collaboration across multiple programs and divisions with shared interests to advance therapeutics for both common and rare diseases into clinical testing.

NCATS Therapeutic Development Branch

This FOA requires partnerships with intramural investigators at NCATS Therapeutic Development Branch (TDB) ( The goal is to catalyze translational research by offering prospective applicants the opportunity to collaborate with NCATS TDB scientists to develop new therapies. The NCATS intramural program contains a breadth of scientific capabilities and is agnostic to the therapeutic indications that may be proposed for collaboration. NCATS TDB can de-risk therapeutic candidates through the optimization and pre-clinical testing of therapies. TDB has expertise including in medicinal chemistry, evaluation of functional activity, toxicity, potency, pharmacokinetics, pharmacodynamics, efficacy, biomarker development, dose optimization, and scheduling for in vivo activity. TDB expertise that may be pertinent to applications submitted to this FOA includes, but is not limited to, optimizing drug delivery strategies, optimizing formulation, designing late-stage pre-clinical studies for regulatory approval, developing milestones, and planning the clinical trial design.

Proposed studies should focus on addressing any regulatory requirements for safety, toxicity, and drug dosing in the patient population before conducting a clinical trial. Specifically, projects submitted in response to this FOA should be designed to generate data of sufficient quality to support successful Investigational New Drug (IND) applications to the Food and Drug Administration (FDA). Of note, TDB has expertise in conducting studies needed for filing an IND application with the FDA. At minimum, the selected therapeutic candidate for a project must have data showing clear efficacy in a relevant animal model(s), promising drug metabolism and pharmacokinetic properties, and initial non-Good Laboratory Practice safety studies demonstrating no gross toxicities. In addition, applicants will provide disease-specific knowledge and expertise, access to models/assays, and access to patient populations.

Leveraging Existing Research Resources:

Applicants are strongly encouraged to leverage existing NCATS clinical trial infrastructure, whenever possible. Learn more at the Rare Disease Clinical Research Network (RDCRN) or Clinical and Translational Science Award (CTSA) websites. NCATS support may be provided to optimize pre-clinical testing of therapies with the goal of generating quality data to support IND applications.

Prior Consultation

 Potential applicants are required to discuss their proposed projects with the NCATS Therapeutic Development Branch ( and include in their application a letter of support from the Scientific Director of NCATS Division of Preclinical Innovation (DPI) that documents agreement to participate in the proposed collaboration.

Applicants are strongly encouraged to consult with NCATS Extramural Program Staff early on in the planning of an application. This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope of the project and intent of this FOA.

Research Scope

This funding opportunity seeks to encourage late-stage translational science project collaborations with NCATS Therapeutic Development Branch (TDB), including therapeutic development of small molecules, biologics, or gene therapies.

The Research Objective of this FOA is to support translation partnerships between therapeutic development scientists who work within NCATS laboratories (intramural) and applicant institutions (extramural). Partnerships that receive support for this FOA will be a bridge between intramural capabilities in NCATS Therapeutic Development Branch with support for early-stage clinical trials at applicant institutions that comes from NCATS Drug Development Partnership Programs. This allows continuity of support for early-stage clinical trials once an IND has been approved by the FDA.

Investigators or companies who have identified a promising candidate can form joint project teams with NCATS’ TDB staff — including Bridging Interventional Development Gaps (BrIDGs) and Therapeutics for Rare and Neglected Diseases (TRND) scientists — to develop IND-ready therapies for consideration by the FDA for clinical testing. The overall combination of partners may assist in developing approaches for optimal drug delivery method, formulation, regulatory strategy, milestone development, and clinical trial planning and site-readiness.

Applications for this initiative must be submitted by the extramural applicant institution, with the NCATS intramural scientist(s) integrated into the application as described in the Collaboration Plan. Participation of the NCATS intramural investigator(s) is limited to the UG3 phase of research only. This intramural-extramural collaboration will be described in a required Collaboration Plan.

Entry Criteria

Projects must meet the following requirements prior to applying:

  • The applicant must have rigorous and sufficient efficacy data in the most relevant disease models before requesting a partnership with NCATS intramural scientists.

Preparatory Activities for the UG3 Phase

  • Partnering Request: the applicant must initiate a Partnering Request to the NCATS Therapeutic Development Branch (TDB) at least 16 weeks prior to preparing an application to learn more about the intramural partnering process ( The request to TDB must include a 2-page project summary. Refer to the section labelled “Partnering Request with NCATS Intramural” in this funding opportunity announcement for more information. Both a Collaboration Plan and a Letter of Support from the NCATS Scientific Director must be included for the application to be complete.
  • Collaboration Plan: the applicant must describe the partnership with NCATS TDB in a Collaboration Plan that will be included in the application.
  • Letter of Support: the applicant must obtain a Letter of Support signed by the NCATS Scientific Director that will be included in the application.
  • For Phase III Clinical Trial or Equivalent for a Rare or Neglected Disease: Consultation with NCATS extramural program official at least 10 weeks prior to the application due date is strongly encouraged (for both new and resubmission applications). If a project proposes the equivalent of a phase III clinical trial for a rare disease, a letter must be obtained from the NCATS program official, confirming whether the indication meets the definition of a rare and neglected disease.

NCATS places a priority on projects with the potential to address system-wide bottlenecks in the translational science research process, or projects that use or seek to develop broader platform technologies that could subsequently be applied to benefit other disease areas.

UG3/UH3 Phases of Research

All projects will have two phases. The UG3 phase, for up to 3 years, is designed to support a project with specific milestones to be accomplished by the end of the period. The UH3 phase is to provide funding for up to 4 additional years following successful completion of the UG3. UG3 projects that meet their milestones will be administratively considered by NCATS and prioritized for transition to the UH3 phase. Investigators submitting to this FOA must address both UG3 and UH3 phases.

This funding opportunity includes activities in both intramural and extramural laboratories.

The UG3 Phase

The initial UG3 phase will provide support for late stage pre-clinical work and clinical trial planning that is conducted at applicant institutions. The scope of the UG3 phase collaboration with intramural includes novel drug delivery strategies, optimal formulation, regulatory strategy, and optimal clinical trial design. Supported partnerships will generate data and materials necessary for the filing of an IND application. The goal of any collaboration with TDB is to enable an IND application by the end of the UG3 phase.

Activities for the UG3 phase may include:

    • Planning or conducting IND-enabling data collection and providing assistance for other regulatory materials, as outlined in the Collaboration Plan. [Note that the NCATS TDB will not conduct initial animal efficacy studies; however, the data provided may be validated before additional data are collected.]
  • Applicant Institution(s):
    • Providing disease-specific knowledge and access to animal models, as needed. The applicant site may conduct some pre-clinical research, as needed, including efficacy validation studies, if novel drug delivery or formulation studies are part of the Collaboration Plan.
    • Conducting all clinical trial planning and site-readiness activities needed to enroll patients before conducting a clinical trial, including collection of feasibility data and complete planning, design, and preparation of the documentation necessary for implementation of an early stage clinical trial.

Grant applications should provide clear, measurable milestones to be accomplished at the end of the UG3.

If UG3 milestones are met and an IND is cleared, support may be provided in the UH3 phase for an early stage clinical trial for a rare or common disease that will be conducted at the applicant institution(s).

The UH3 Phase

Funding for the UH3 phase is contingent on successfully meeting the milestones in the UG3 phase (see Section VI. Award Administration Information, 1. Award Notices for further information). The UH3 phase supports the next step in the development of the intervention. The application is expected to provide quantifiable milestones to determine success of the UH3.

In the UH3 phase of the project, NCATS may support clinical trial activities through the end of Phase II for all diseases or conditions, and through the end of Phase III for a rare disease or condition. NCATS strongly encourages applicants to involve patients or their representatives in the planning of the trial, as appropriate.

Activities for the UH3 may include:

  • Phase I clinical studies: Studies conducted in the target patient population and with healthy volunteers, where the purpose is to evaluate safety, determine a safe dose range, and identify side effects prior to conducting a Phase II clinical trial.
  • Phase II clinical studies: Studies conducted in a larger patient population, which typically enroll 150 subjects or fewer for trials in adults. The purpose of the Phase II clinical study is to demonstrate efficacy in the target population.
  • Clinical trials for Rare Disease: Due to small numbers of available patients, the terms Phase I, II, and III clinical trials may not always be appropriate. Therefore, well-controlled studies in a rare disease population may be proposed. The purpose is to demonstrate substantial evidence of efficacy in treating or preventing the condition, and to establish evidence of safety for that use (see NOT-TR-18-025 “NCATS Policy for Support of Phase III Clinical Trial Activities for a Rare Disease or Condition”). Evidence of efficacy for a rare disease may be established in one or more adequate and well-controlled clinical trials in the identified population (see Rare Disease: Common Issues in Drug Development Guidance for Industry for more information:

Research Areas of Interest

Key priorities of this FOA are as follows:

  • Projects with the potential to address system-wide bottlenecks in the translational science research process.
  • Projects that use or seek to develop broader platform technologies that could subsequently be applied to benefit other disease areas.
  • Drug repurposing or repositioning studies.
  • Projects testing novel drug delivery strategies and testing optimal formulation strategies of commercially available assets that have been publicly posted on open innovation websites.
  • Clinical trials that test more than one related disorder at the same time. Patient population selection strategies that are similar to the basket approaches being tried in cancer research are of interest for rare and neglected disease studies when shared pathways are involved in the disease progression and the endpoints are the same or similar.

Activities Considered Outside of Scope of this FOA

Examples of activities that are non-responsive to this FOA and will not proceed to peer review:

  • Projects that do not already have efficacy data for the indication or that do not document evidence that efficacy data are not required for regulatory approval.
  • Projects that have not identified the lead candidate for IND-directed development, or that would require additional medicinal chemistry optimization.
  • Projects that seek to make only incremental improvements upon the characteristics of an existing therapy (e.g., improved pharmacokinetics) or that would be a follow-on to current effective standard(s) of care.
  • Projects that do not include in their application a Collaboration Plan that outlines the work to be planned or executed at NCATS intramural.
  • Projects that propose testing the effectiveness of a dietary supplement.
  • Applications that propose Phase III clinical trial activities for a common disease or condition.

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 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

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?
Required: Only accepting applications that propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

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 project period is limited to 3 years for the UG3 phase and 4 years for the UH3 phase.

The maximum project period is 7 years.

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

  • U.S. Territory or Possession


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

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

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

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

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • – Applicants must have an active DUNS number and SAM registration in order to complete the registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to: 

Rani Khan, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Phone: 301-594-7319

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.

For applications that propose a Phase III clinical trial or its equivalent for a rare or neglected disease only:

The applicant must provide documentation that the application meets the criteria for Phase III rare disease or condition clinical trial. The NCATS program official may provide a letter confirming that the indication meets the definition of a rare and neglected disease. NCATS will not provide support for a Phase III trial for a disease that affects more than 200,000 people in the U.S.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Budget Justification:

Because of the anticipated complexity of the budget information and the need to clearly delineate costs for the extramural awardee, applicants must submit a detailed R&R budget. Submission of a Modular Budget is NOT allowed for this FOA.

The budget request for this FOA must distinguish between extramural costs and the NIH intramural investigator costs. Extramural costs are associated with the extramural investigator and the applicant organization. NIH intramural investigator costs are those required by the intramural investigator for carrying out the proposed work and which are specifically identified with the project.

Extramural Costs

Extramural costs may include such items as salary support for the extramural PD/PI and staff at the applicant organization, supplies, data analysis, and other allowable costs for work performed at the (extramural) applicant organization, as well as travel costs for the extramural investigator(s). Extramural costs may also include travel costs for any patients not already at the clinical study site. The PD/PI and up to one other key personnel with complementary expertise are required to attend semi-annual program meetings. The meetings will alternate between NCATS, Rockville, MD and extramural site(s). Funds to attend these meetings should be budgeted in the application. Extramural costs should also include travel costs for in-person meetings with NCATS intramural collaborators.

F&A (Indirect) Costs: Applicant organizations are reminded that Facilities and Administrative (F&A) or “indirect costs” are allowable for only the allowable extramural costs of the project.

Intramural Costs

The requests by NIH intramural scientists will be limited to the incremental costs required for participation specifically identified within the Collaboration Plan, and detailed below under Section IV.7. Resources required need to be determined before the research protocol can be approved by the NCATS. Prospective applicants are strongly encouraged to contact NCATS staff to discuss intramural investigator costs. Once the intramural investigator costs are known, the extramural applicant will enter this amount as a "subaward" budget in the application, and attach appropriate justification and documentation, including any spreadsheets as appropriate. The NCATS TDB’s costs and intramural investigators’ costs will not be included in the award paid to the grantee. Support for intramural participation will be provided by a budget allocation within the NIH. Any IND-enabling work, regulatory assistance, or other work conducted in NCATS intramural laboratories will be supported by the NCATS intramural research program, and it will not come from the applicant institution’s budget (extramural funds).

Peer reviewers will evaluate the appropriateness of the IRP staff and budget request for the work proposed and will therefore need to know the level of effort being proposed to conduct the work.

The Budget should include:

  • Resources for conduct and completion of the clinical trial, including funding for orderly close-out of clinical sites, and preparation of a final study report.
  • Site assessment and protocol training as part of the UG3, prior to initiation of a clinical trial.

Additional Guidance on Budget Preparation

The application budget should reflect actual needs of the proposed project and align with the distribution of the work during the project. The budget requests for this FOA are more complex and will require more coordination than those of other programs. Therefore, extramural investigators are encouraged to begin discussions about logistics and budget issues with their intramural collaborators and with NIH staff in the early phases of application preparation.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy


  • Significance of the proposed work to the patient population:
  • why the specific therapy addresses an unmet medical need, global burden of disease;
  • which patients will benefit;
  • how patients will benefit;
  • the potential public health impact if the proposed research successfully translates to the clinic.
  • Significance of the indication:
  • How many patients are impacted by the indication;
  • Which patients benefit if the therapeutic is successfully translated to the clinic;
  • How is the proposed therapeutic superior to an existing standard of care or superior to other experimental therapies?
  • Significance of the therapeutic:
  • The novelty of the target class for the proposed indication, or how the mechanism of action of the therapeutic has been understudied for the indication; and
  • If the same target/mechanism of action has been studied in the proposed patient population, discuss the value added for the proposed studies.


  • How this project shifts translational science paradigms: Address any ways that the project will generally improve the success or efficiency of translational science. Discuss the ways in which any learnings from the current therapeutic development campaign could be applied to other translational science efforts.


Applicants should delineate the research strategy by work that will be conducted in each year of the UG3 and UH3.

Overall Strategy and Analyses:

Projects should have clear, testable hypotheses and the research plan should use quantifiable measures for making a go/no-go decision. A statistician should be consulted to make sure all experiments have adequate power and statistical rigor. Justification and statistical calculation for the proposed number of animals for applicable in vivo models should be included.

UG3 Phase Pre-clinical Studies:

The intent of the pre-clinical studies is to collect data needed to inform the clinical trial design and to collect data needed in an IND application. Experimental studies to support such a decision should be well designed, of sufficient power and statistical rigor, and include the appropriate controls. Applicants should describe how they will achieve unbiased results when describing the experimental design of the proposed studies. If any non-clinical safety studies are necessary, please follow the following guidance:

For Pediatric Indications:

Juvenile animal studies to assess the potential drug toxicity in one or more species may be needed for pediatric indications. Describe proposed pre-clinical juvenile toxicity studies to support clinical trials in children, if these have not been completed. Investigators should consider the FDA's “Guidance on Nonclinical Safety Evaluation of Pediatric Drug Products” in designing pre-clinical toxicity studies. (

Dosing Information:

Describe studies to determine the right dose, duration, time of treatment, or patients to treat.

  • Specify dose range of the therapeutic. For pediatric indications, specify dose range for the therapeutic and proposed route of administration, and discuss any known or expected issues with oral formulations (solubility/permeability, taste/bitterness).
  • If the doses and/or dosing schedule(s) available in the pre-clinical safety data are insufficient to support a subsequent clinical trial for the new indication, describe the design of additional pre-clinical safety study or studies that will be required to support the clinical trial. Include the type of animal species, the therapeutic doses and dosing schedule to be used, and provide the justification for each.
  • State the duration of studies, based on any safety data available for the proposed therapeutic, and whether the new use of the proposed therapeutic is for treatment of an acute or chronic disease.
  • Detail brain penetrance studies (for neurological indications) when such data is not available.

UG3 Phase Clinical Trial Planning:

The clinical trial planning period is intended for time and financial support to collect feasibility data, complete all planning, design, and documentation that is necessary before starting a clinical trial. The clinical trial planning section must include plans for collecting feasibility data. This data collection should use existing datasets and resources (e.g., databases), whenever possible. Depending on the project, it may be helpful to assess feasibility using patient samples (e.g., estimate the prevalence of a genotype that affects drug metabolism). The applicant should demonstrate that there is an appropriate and interested patient population by conducting interviews, surveys, focus groups or prior performance at the site. The feasibility data collection will provide the following types of information:

  • Identify availability of individuals with the disease or condition being tested at the study site.
  • Identify whether the distribution by age, sex/gender, race, and ethnicity is representative for the disease/condition being tested.
  • Identify the feasibility of inclusion/exclusion criteria.
  • Determine if drug-drug interactions exclude too many subjects with the condition for the experimental therapy to be feasible to use in the proposed study population, based on existing literature and data.
  • Estimate how many study sites will be needed to complete the study within a reasonable timeframe.

In addition to the feasibility data collection, the clinical trial research planning period during the UG3 should state how the planning period will be used and specify the timing of the activities to be carried out during the planning period, including participants in the planning process and their roles. These activities may include the following:

  • Detail how the clinical trial documents will be developed; and describe how the trial will be organized and managed.
  • Prepare a statistical analysis plan.
  • Prepare a recruitment and retention plan. Model the feasibility of an outcome or intervention in the field. Estimate available populations, attrition rate, or response rate. Determine if adequate adherence to treatment is achievable.
  • Develop a plan to address potential delays and alternatives for conducting the study in the face of adverse outcomes or problems. This plan should inform the likelihood of accomplishing the trial in the time frame proposed for a subsequent application for funding of the Phase I and Phase II clinical trial or rare disease clinical trial.
  • Develop informed consent(s) and/or assent forms (if applicable).
  • Write the clinical trial protocol, including a data management plan, data safety and monitoring plan, and a plan for collecting adverse events and reporting these events to regulatory authorities and NIH.
  • Develop a manual of operations with quality control and assurance procedures. A data quality management plan should be developed for all sites to ensure the quality of the data collected.
  • Adapt and test existing survey instruments or protocols for a new population. For example, determine if the enrollment goals can be achieved; determine if the patients are interested in the therapy; and determine if patients would be interested in participating in the protocol.
  • Prepare a data sharing plan.
  • Request a pre-IND meeting to obtain guidance for designing the clinical trial and obtaining clearance of the IND. The NCATS extramural program official should be copied on any communication with FDA.
  • Prepare FDA and regulatory documents for an IND package submission.
  • Obtain Office of Human Research Protection (OHRP) assurances (if not already in place) and initiate Institutional Review Board (IRB) approval using a single, central IRB.
  • Develop a detailed project timeline and appropriately resourced budget for conducting and completing the clinical trial, including funding for orderly close-out of clinical sites, and preparation of a final study report.
  • Develop a budget for site assessment and protocol training.
  • Plan for centralized site monitoring (when appropriate) if multiple sites are involved. Learn more:

UH3 Phase I Clinical Trial:

If a Phase I clinical trial is needed, provide an overall plan to assess the validity of the biological hypothesis. Include the following:

  • Specify dose range of the therapeutic.
  • Describe the approach and personnel resources available for clinical trial document preparation and timely filing of an IND and rapid Institutional Review Board (IRB) approval. If a multisite trial is proposed, a single or central IRB must be used per 45 CFR 46.114
  • Describe the use of PK and PD biomarkers, when available, to assess dose and exposure of the therapeutic at the target site of action; binding at the target; and expression of functional pharmacological activity of the therapeutic at the target site of action.

UH3 Phase II Clinical Trial:

Provide an overall plan for the preliminary efficacy signal Phase II clinical trial. Include the following:

  • Describe the clinical trial design, based on available safety data for the therapeutic.
  • Define the patient selection strategy.
  • Consider the use of molecular markers of disease, pharmacogenomics, or other biomarkers, when applicable.
  • Describe a plan for the involvement of Patient Advocacy Groups (PAGs) in the protocol design and recruitment strategy. If PAGs are not included, provide a rationale for their exclusion.
  • Specify dose range, PD parameters used to perform dose ranging, route of administration, and amount of therapeutic needed.
  • Justify the number of patients chosen for the Phase II trial (based on the proposed outcome measures and the appropriateness of the statistical methods).
  • Justify the sample size and duration of the Phase II clinical trial for the specific disease population.
  • Provide assurance that the proposed study can be completed within its budget and within the time limits stated in this FOA.

UH3 Rare Disease Clinical Trial:

  • Include the following:
  • Provide a well-controlled clinical trial plan that is designed to show substantial evidence that there is safety and efficacy, and the benefits to patients significantly outweigh any risks.
  • Define the study duration and choice of subpopulations (when relevant), and number of subjects. Additionally, study design may include the following:
  • Describe clinically meaningful patient assessment tools and endpoints.
  • Detail outcome measures that are more specific or sensitive to changes in manifestations of the disease or can more quickly demonstrate safety or efficacy than existing measures.
  • Identify new or optimized biomarkers that may provide proof-of-concept, guide dose selection, allow early identification of safety concerns, or provide supportive evidence of efficacy.

Data Elements: Describe which disease manifestations are likely to develop, and when; which are likely to persist; and which disease signs predict development of the most important disease manifestations.

Future Plans: Describe the commercial potential of the therapeutic as a development candidate and potential challenges for commercialization of the therapeutic for the new disease indication

Preliminary Studies:

Preliminary studies include any data and information that validate feasibility for studies that address the Specific Aims.

  • Models: Provide an overview of any in vitro or in vivo models used, or data from any prior clinical experience.
  • Measurements: Provide an overview of any methods used to monitor therapeutic efficacy, and whether the method is acceptable for regulatory approval.
  • Pre-clinical data: Applicants must describe animal efficacy studies or explain why efficacy studies are not needed for regulatory approval of a new indication for an existing therapeutic. This should address the following:
  • Evidence that the target or specific pathway is involved in the disease pathology.
  • Animal efficacy data, drug metabolism and pharmacokinetic properties (when available), and initial non-Good Laboratory Practice safety studies supporting the rationale for further IND-directed development of the candidate.
  • How translatable the proposed models are to humans.
  • Clinical trial planning data:
  • If available, provide a brief background on human dosing, safety, and tolerability from prior studies supporting dose and dose schedule for the therapeutic in the proposed new disease area, including any exclusions or restrictions for use of the therapeutic.
  • Include data that supports the selection of clinical trial endpoints for assessing drug or biologic activity, or clinical outcome assessments that measure patient symptoms, overall mental state, or effects of a disease or condition on how the patient functions. Learn more:

Partnering Request with NCATS Intramural:

The applicant institution must initiate a Partnering Request with the Therapeutic Development Branch (TDB) at least 16 weeks prior to preparing an application for funding. Prior to contacting NCATS intramural, applicants should develop a brief, structured summary of the proposed project, not to exceed two pages. This summary should describe the therapeutic agent, the disease, the goals for improved therapies, the available efficacy and safety data in the disease-relevant models, and the particular NCATS resources necessary to advance the project to a successful regulatory filing stage. The narrative should not include proprietary, confidential information or trade secrets, but should be generally informative to persons working in related fields. Learn more:

  • During this initial engagement, NCATS intramural will:
    1. determine if the project is a strategic fit with NCATS intramural mission;
    2. determine whether the intramural program has the capacity and bandwidth to collaborate on the specific project goals;
    3. begin working on a Collaboration Plan that will be included in a complete application for support, outlining the expectations and contributions of each party. The Collaboration Plan will outline what experiments will be conducted at NCATS and what experiments will be conducted by the applicant for which UG3 and UH3 support may be requested.
  • As part of this initial engagement, applicants with projects within the strategic fit for NCATS intramural will be expected to provide a more detailed project description, expanding on the content of the primary non-confidential summary. This description may require provision of non-public information and if so, applicants will be expected to sign a two-way Confidential Disclosure Agreement (CDA). Learn more:

Letters of Support:

1. Letter of Support from NCATS Intramural:

Applications submitted in response to this FOA must include a current (i.e., within 2 months of application due date) letter from the Scientific Director of the NCATS Division of Preclinical Innovation to confirm that the NCATS Therapeutic Development Branch Laboratory will be able to accommodate the proposed research and that the NCATS intramural scientist(s) will be able to collaborate on the project, as delineated in the required Collaboration Plan. Applications submitted without this letter of support will be considered incomplete and will not be reviewed.

2. Letter of Support from Applicant Institution on CRADA:

This collaborative translational research between NCATS intramural scientists and extramural investigators will involve a Cooperative Research and Development Agreement (CRADA), which will need to be executed for projects deemed scientifically meritorious by peer review. NCATS will provide CRADA template documents to help streamline the interaction between NCATS intramural scientists and extramural investigators. These template agreements can be found on Questions regarding any of these agreements can be referred to the NCATS Office of Strategic Alliances at Applicants should review this document and consult with their institutions about their willingness to agree to the conditions well in advance of submitting an application to this FOA. The CRADA will need to be executed after the application has been identified for funding. While the CRADA may not be in place before the award is made, a statement from the applicant’s Sponsored Research Office (or equivalent) that they agree, in principle, to the conditions of the CRADA should be included in the application. Failure to include this statement could result in delays should the application be identified for funding.

3. Letter of Support from the Therapeutic Provider:

For projects that obtain a non-commercially available therapeutic (asset) from a pharmaceutical partner only, the application must include a letter documenting access to the asset and associated data needed for filing an investigator-sponsored IND application to conduct the proposed clinical trials (e.g., a letter indicating that a Collaborative Research Agreement is being executed, and the PD/PI has the right to cross-reference specific sections of the pharmaceutical company partner's IND/Drug Master File, etc.). The letter of support should indicate the timeframe for expected delivery of the asset and how long the partner is committed to provide manufacturing and technical support.

In many cases pharmaceutical companies may publicly offer commercially owned assets on an Open Innovation website that invites applicants to test new therapeutic uses or to provide ideas for novel drug delivery or formulation, for which partial support could be provided by the intramural program. It is appropriate for applicants to include open innovation collaborations with external asset providers. NCATS encourages the use of existing template legal agreements for such collaborations, when they are already publicly available (see or

Please note that Resubmissions need an updated letter of support from the participating pharmaceutical partner (i.e., within 2 months of the resubmission application due date), who is under no obligation to make an asset available for longer than one application cycle.

4. Letter(s) of Support from Collaborator(s):

Letters from other collaborators/consultants confirming participation should also be included.

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

The following modifications also apply:

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

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Collaboration Plan

Applications must include a proposed Collaboration Plan, describing how the collaboration with NCATS intramural will be maintained throughout the duration of the award. The filename "Collaboration Plan-PI-NAME.pdf" should be used and will be reflected in the final image bookmarking for easy access by reviewers. The Collaboration Plan is limited to 2 pages.

Suggested areas to address include:

  • Organizational structure;
  • Specific NCATS Therapeutic Development Branch Program resources needed to advance the project;
  • Planned interaction and responsibilities of key personnel;
  • Description of how research teams will communicate (e.g., videocast, web meeting, etc.);
  • Description of any pre-existing intellectual property;
  • A plan for handing scientific differences of opinion/conflicts that may arise between NCATS scientists and the extramural investigator; and
  • While the CRADA may not be in place before the award is made, a statement from the Sponsored Research Office agreeing in principle to the terms of the template CRADA must be included.
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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 (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 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 on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

 Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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 a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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


Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?


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

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA: Does the Collaboration Plan adequately cover the roles and responsibilities of the intramural and extramural partners?


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

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this FOA: Does this application include an adequate partnership with NCATS intramural for optimal drug delivery strategy, optimal formulation, design of regulatory studies, milestone development, or clinical trial planning?


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

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

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA: Is an IND likely to be cleared by the end of the UG3? Are the milestones at the end of the UG3 phase appropriate and feasible? Does the application include any element that can improve the success or efficiency of translational science? Are there any aspects of the study design that can be applied to future therapeutic development studies to improve the efficiency of getting new therapies to patients?


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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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


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


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


Not Applicable.


Not 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 will receive a written critique.

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
  • Availability of intramural research program resources to complete the portfolio of IND-enabling studies that are being recommended for support.

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.


Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the Protocol Registration and Results System Information Website ( NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see and

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.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at or call 1-800-368-1019 or TDD 1-800-537-7697.

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 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities.

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

  • 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.
  • Ensure timely submission of Phase I and Phase II clinical trial data to
  • 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 clinical trial oversight committee (CTOC) as needed, in consultation with the NIH Program Official, NIH Project Scientist, and pharmaceutical company partner (if applicable).
  • The PD(s)/PI(s) will chair the CTOC; 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.
  • Hold teleconferences with NIH to address operational issues on a monthly basis or as dictated by the needs of the study.
  • Adhering to relevant 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.
  • Hold teleconferences with NIH to address operational issues on a quarterly basis or as dictated by the needs of the study. Providing monthly written reports to the CTOC summarizing: the progress of the project; obstacles encountered and solutions; and monthly recruitment updates. The reports should be provided in a format decided upon by the CTOC.
  • Providing a progress report, due 60 days prior to completion of the budget period 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.
  • Addressing all study design, operational, logistical, 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 a revised NoA is received. Ensuring timely publication of abstracts and scientific articles to make results of projects and inventions available, including negative data.

NCATS Intramural will be responsible for:

  • Providing project management and drug development operational support during the UG3 phase as described in the project milestones.
  • Carrying out IND-enabling studies as described in the project milestones.
  • Assisting with planning of clinical trials, regulatory support to increase the likelihood of satisfying Food and Drug Administration requirements, and IND filing support as described in the project milestones.
  • Participating in the analysis, interpretation, and reporting of findings in the scientific literature, to the community at large and to the public policy community within the Federal government through various media, as appropriate.

NIH extramural 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 and 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 CTOC activities, including conference calls.
  • 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 DSMB or another monitoring body.
  • Participate in 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 project update meetings and conference calls.
  • Monitor recruitment status of the trial on an ongoing basis.
  • Monitor performance through consideration of quarterly meetings of the CTOC, annual reports, and compliance with NIH procedures.
  • Approve modifications to the research plan and/or study protocol(s), in consultation with the CTOC, based on emerging data and/or other issues that impact progress of the project.
  • Reserve the right to obtain periodic external review and select reviewers for an assessment of progress and achievement of milestones.
  • Reserve the right to terminate or curtail a project for any of the following reasons: (1) inadequate progress in meeting the pre-negotiated milestones and timelines; (2) risk(s) to subject’s safety; (3) slow accrual; (4) data from a futility analysis; or (5) failure to comply with the Terms and Conditions of Award.
  • Review progress on the UG3 milestones and determine if the project will continue to the UH3 phase.

Areas of Joint Responsibility include:

Since the purpose of this FOA is to establish and/or further develop collaborative arrangements between extramural and intramural investigators, many responsibilities are shared between awardees and NIH staff and will require close coordination. Responsibilities will be divided between awardees and NIH staff, as described above.

Annual progress reports will be prepared and submitted by the extramural institutions, with the participation and input of the intramural investigator(s) and should include the project findings, publications, impact of the project, a description of what NCATS intramural resources were utilized and the new intramural-extramural partnerships that developed. This will be evaluated by the program official or program director.

The Collaboration Plan will cover how the following activities will be shared during the UG3 phase between NCATS intramural and the applicant institution: 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.

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 or progress on the milestones.

Clinical Trial Oversight Committee (CTOC):

Each awardee's project will have a CTOC. The CTOC will include: the PD(s)/PI(s), key personnel, the NIH Project Scientist (voting), the NIH Program Official (ex officio), and any external scientist(s) that the PI invites.

The CTOC will:

  • Recommend changes to the experimental design, clinical trial plan, to address obstacles encountered and solutions and compliance with relevant policies and regulations.
  • 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 member chosen by the individual awardee, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. 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. Follow 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 RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at 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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: (preferred method of contact)
Telephone: 301-637-3015 Customer Support (Questions regarding registration and Workspace)
Contact Center Telephone: 800-518-4726

Scientific/Research Contact(s)

Extramural Program Official 
Steven Pittenger, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-5810

Intramural Partnering Requests 
Donald C. Lo, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301.827.1844

Peer Review Contact(s)

Rani Khan, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Phone: 301-594-7319

Financial/Grants Management Contact(s)

Gloria Velez
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0875

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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