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 Screening with Biofabricated 3-D Skin Disease Tissue Models  (U18 Clinical Trial Not Allowed)

Activity Code

U18 Research Demonstration – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-TR-19-020

Companion Funding Opportunity

 None

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

93.350 

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to build upon the work that has begun under previous FOA RFA-TR-17-007 “NCATS Pilot Program for Collaborative Drug Discovery Research Using Bioprinted Skin Tissue” and utilize physiologically relevant and validated 3-D biofabricated skin disease tissue models in multi-well drug screening platforms. The FOA will support intramural- extramural collaborations to implement the use of 3-D biofabricated skin tissue models and provide evidence of success for 3-D drug screening platforms.

Key Dates

 

Posted Date

May 21, 2019

Open Date (Earliest Submission Date)

July 1, 2019

Letter of Intent Due Date(s)

July 1, 2019

Application Due Date(s)

July 31, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

November 2019

Advisory Council Review

January 2020

Earliest Start Date

March 2020

Expiration Date

August 1, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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


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

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

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

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information


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

    Purpose

    The purpose of this FOA is to promote partnerships between intramural investigators at the National Center for Advancing Translational Sciences (NCATS) Three-dimensional (3-D) Tissue Bioprinting Laboratory and extramural researchers to utilize physiologically relevant 3-D biofabricated tissues and enhance drug screening and discovery process. This FOA is to leverage the capabilities of the NCATS 3-D Tissue Bioprinting Program through collaborations with extramural investigators in the basic and clinical research communities who provide the disease and tissue physiology expertise necessary to develop and validate 3-D biofabricated tissues platforms for drug screening. Through these partnerships, the process of discovery and development of new medicines can be greatly advanced by developing new assay models that better predict the effects of drugs in humans. 3-D tissue models that mimic characteristics of live human tissues are produced on microplates to test effectiveness and toxicity of small molecules or other therapeutics.

    Based on NIH funding appropriations, funds from the National Institutes of Health (NIH) will be made available through the U18 cooperative agreement award mechanism. While the previous FOA, RFA-TR-17-007 primarily focused on development of 3-D biofabricated skin disease models that can be utilized in a drug screening format, this FOA will support the implementation of drug screening with already developed and validated biofabricated 3-D skin disease tissue models. Intramural scientists at the NCATS 3-D Tissue Bioprinting Laboratory will adapt existing and validated low-throughput (at least 6-well plate) assays with biofabricated 3-D skin disease equivalents to medium- (24-well) and high-(96-well) throughput screening (HTS) platforms and implement drug screening to identify novel compounds. Extramural scientists will provide expertise, materials and protocols necessary to adapt biofabricated 3-D skin disease models and associated assays for HTS at NCATS, and will subsequently validate the activity of compounds identified in the screens.

    Background

    More than 90% of the drugs being developed fail due to toxicity or lack of efficacy, often because of the use of overly simplistic pre-clinical in vitro cell assays and/or in vivo mouse models that have limited success in predicting outcome of the later stages of drug development. 3-D biofabrication of tissue models using human primary cells, allogeneic or autologous human induced pluripotent stem cells (iPSC)-derived cells that faithfully recapitulate native tissues can provide more clinically relevant physiological and pharmacological data. Recent advances in the fields of engineering, biomaterials science, stem cell biology, physics and medicine have enabled the field of 3-D biofabrication of living tissues. Living cells and scaffolding materials can now be combined into complex 3-D functional tissues produced on microplates (tissue-in-a-well), which are used in pre-clinical drug testing. These tissues are created using either iPSCs or primary cells taken directly from living tissue. The goal of creating 3-D biofabricated human-like tissues in microplate format for screening is to provide physiological and pharmacological data that predict the effects of drugs better than data from traditional studies using 2-D models. In addition, these models will have an immediate and long-lasting impact on reducing the cost of drug discovery as well as shortening the time it takes to bring new medicines to more patients.

    Leveraging Existing Research Resources:

    Applicants are strongly encouraged to leverage existing research resources for their studies whenever possible. Applicants are required to utilize the state-of-the-art high-throughput drug screening model and assay development, as well as drug screening capabilities at the NCATS. In addition, leveraging the resources and support from patient advocacy groups, private research foundations, academic institutions, for-profit organizations and other government agencies and the NIH Intramural program is also encouraged.

    NCATS 3-D Bioprinting Laboratory

    This FOA requires partnerships with intramural investigators at NCATS 3-D Bioprinting Laboratory (https://ncats.nih.gov/bioprinting). The objective of the 3-D Tissue Bioprinting Laboratory at NCATS is to produce 3-D tissue models in multi-well plate platforms as disease relevant assays for drug screening. 3-D tissue models are biofabricated using tissue engineering and 3-D bioprinting technologies with human primary and iPSC derived cells, and undergo morphological and physiological validation. Relevant disease phenotypic detection endpoints are developed that are compatible with HTS capabilities at NCATS for drug screening. 

    NCATS has unique libraries of pharmacological agents, including approved drugs and mechanistically annotated compounds, which will be used to pharmacologically benchmark the 3-D biofabricated tissue models, as well as to repurpose existing drugs and/or understand the pharmacology underlying diseases (https://ncats.nih.gov/preclinical/core/compound). 

    For projects supported under this FOA, the external research community will provide expertise in specific skin disease models and disease-relevant assays that are already established and validated in low-throughput format. The NCATS 3-D Bioprinting Laboratory will provide expertise in integrating 3-D biofabrication technologies such as tissue engineering, 3-D bioprinters and biocompatible polymers and hydrogels, with phenotypic assays that are compatible with HTS platforms at NCATS to enable the use of 3-D tissue models for drug screening. In addition, NCATS 3-D Bioprinting Laboratory will provide drug screening expertise and implement drug screening on the model. Once promising compounds are identified, they will be provided to extramural collaborator(s) for subsequent validation studies.

    Prior Consultation

    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.

    Potential applicants are required to discuss their proposed projects with the Director of the NCATS Bioprinting Laboratory (https://ncats.nih.gov/bioprinting) 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.  See Letters of Support below.

    Research Objectives

    Research Scope

    For this FOA, the focus is to develop 3-D tissue models for drug discovery and development of new therapeutics.  Extramural investigators will collaborate with the NCATS 3-D Bioprinting Laboratory to adapt low-throughput (at least 6-well plate) biofabricated 3-D functional skin disease tissues that are already developed in the PD/PIs laboratory to a medium- and high-throughput multi-well plate format together with relevant HTS-compatible detection endpoints. Bioprinting as well as other tissue engineering techniques can be utilized/combined to establish the models. The constructs must be developed using human cells, including primary cells and/or cells derived from iPSCs.  Specifically, this FOA is seeking collaborations that leverage both the NCATS biofabrication and screening capabilities and the collaborators’ own internal capabilities for:

    • Biofabricating morphologically and physiologically validated low-throughput 3-D skin disease tissues model to a medium- and high-throughput format;
    • Scaling up production of iPSC-derived relevant cells needed to prepare the high-throughput 3-D skin disease tissue models for screening;
    • Developing protocols for fast, medium and high throughput quantitative measurements from the biofabricated 3-D skin disease tissues including fluorescence and luminescence cell imaging, and other HTS compatible assay endpoints. Examples of HTS compatible assay readouts include high content imaging with cellular reporters or immunostaining, cytokine secretion, cell viability and transepithelial/transendothelial electrical resistance (TEER) measurements;
    • Screening compound libraries using the biofabricated 3-D skin disease tissue models in a multi-well plate format; and
    • Validation of hits identified in screens.

    Prior to submitting an application, applicants are expected to have already completed the following activities relevant to the project:

    • Developed morphologically and physiologically validated skin disease tissue models in a multi-well platform (at least 6-well plate), including thorough validated normal and disease tissue equivalents using established techniques such as histology; cell imaging in order to demonstrate appropriate overall architecture; cell composition; tissue markers; disease markers; and utilized known modulators of relevant pathways or targets to demonstrate correct tissue physiology and appropriate pharmacological responses.
    • Established robust and reproducible protocols for the production of primary or iPSC-derived cells needed for the biofabrication of skin disease tissue constructs.
    • Developed and established robust disease-relevant endpoint readout(s) that are HTS compatible.
    • Established reproducibility and robustness of the endpoint assays developed with the 3-D skin disease tissue model. 

    Tissue-in-a-chip devices in a microtiter plate format can be included if they have open access to 3-D bioprinters for tissue bioprinting and are commercially available and amenable to detection endpoints commonly used at NCATS for HTS (https://ncats.nih.gov/bioprinting).  These approaches should be discussed with the investigators at the NCATS 3-D Bioprinting Laboratory before submission.

    This funding opportunity includes activities in both intramural and extramural laboratories. Initially, the extramural scientist will provide expertise in skin disease-specific 3-D biofabricated constructs and relevant assays, transferring the protocols and materials to NCATS for a timely adaption to a high-throughput format. NCATS intramural scientists will work towards the adaptation of the biofabricated 3-D skin disease tissue models and endpoint readouts to a drug screening platform and implementation of screens of up to 1000 compounds.

    Activities supported include, but are not limited to:

    • Adapting 3-D skin disease tissue model biofabrication and the corresponding detection assay protocols to NCATS 3-D biofabrication and screening capabilities at the 3-D Tissue Bioprinting Laboratory.
    • Screening libraries of compounds and cheminformatics analysis of the results at NCATS.
    • Validating screening results by extramural investigator(s). Following completion of screening, NCATS will provide compounds to extramural investigator(s) for additional validation studies.

    The goal of this U18 is to be able to screen up to 1000 compounds at one compound dose per assay to pharmacologically validate the biofabricated 3-D skin disease tissue models (establish effect of known modulators), and to identify compounds that modulate the relevant skin disease phenotypes.  Compounds for screening will be selected following close consultations among PD/PIs and the NCATS 3-D Tissue Bioprinting Laboratory and depend on the type of assay, biology and scope of the project. NCATS has the capability to select and assemble customized libraries of compounds for screening. The libraries screened will include compounds with annotated target and mechanism of action and approved drugs for drug repurposing screening (https://ncats.nih.gov/preclinical/core/compound). 

    Technical readiness of the 3-D disease tissue model assays.  It is expected that biofabricated 3-D skin disease tissue models and associated assay(s) will have been configured and characterized in a multi-well plate format (at least 6-well plate) by extramural investigator(s) and can be rapidly adapted to the biofabrication and screening capabilities at the NCATS. Technical readiness of the biofabricated 3-D skin disease tissue models and detection readouts for drug screening will be demonstrated by:

    • Morphological and physiological validation of the tissues using established techniques such as histology (to demonstrate appropriate overall architecture, cell composition, tissue markers, disease markers), and other technologies to demonstrate correct tissue physiology.
    • A disease phenotype endpoint readout that is compatible with a multi-well-based (24-  or higher well density) plate format that is amenable for use with HTS liquid handlers and readers and is sufficiently robust for compound screening in that it meets the established HTS robustness criteria like Z-factor, a calculated parameter that is commonly used to quantify assay performance, and that accounts for both the signal-to-background and the amount of variability in the assay between the control and disease states.  Examples of HTS compatible assay readouts include high content imaging with cellular reporters or immunostaining, cytokine secretion, cell viability and transepithelial/transendothelial electrical resistance (TEER) measurements.

    Assays that require manual tissue processing and transfer to a different platform for assaying (e.g. histology) most likely will not be HTS compatible but should be discussed with the investigators at the NCATS 3-D Bioprinting Laboratory before submission for alternative options. Clearing protocols for high content screening are acceptable if needed and should also be discussed with the investigators at the NCATS 3-D Bioprinting Laboratory before submission.

    Additional Considerations

    Cells. The availability and use of human primary cells, or pluripotent stem cells such as iPSCs, is strongly encouraged. Multipotent or unipotent stem cells also may be utilized where appropriate. The current NIH guidance on stem cell usage can be found at http://stemcells.nih.gov/policy/pages/2009guidelines.aspx. All normal and pathologically-relevant, as well as any reporter iPSC lines required for the project must be established and validated prior to submission.  For primary cells, the extramural investigators will have to demonstrate availability of the cells in sufficiently large quantities for subsequent utilization in drug screening platforms. 

    Collaboration Plan.  Applications for this program will be submitted by the extramural institution with the NCATS intramural scientist(s) integrated into the application as described in the Collaboration Plan.  Please see below.

    IMPORTANT: Potential applicants are required to consult with the Director of the 3-D Tissue Bioprinting Laboratory at NCATS https://ncats.nih.gov/bioprinting. Early contact provides an opportunity for NCATS staff to discuss the program scope and goals, and to provide information and guidance.

    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

    New

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

    Clinical Trial?

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

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NCATS intends to fund an estimate of two awards, corresponding to a total of up to $1,500,000 for fiscal year 2020. Future year amounts will depend on annual appropriations.

    Award Budget

    The direct cost is limited to $400,000 (exclusive of any contract/consortium F&A) per year.

    Award Project Period

    The scope of the proposed project should determine the project period. 

    The proposed project period must not exceed two 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:

    o   Hispanic-serving Institutions

    o   Historically Black Colleges and Universities (HBCUs)

    o   Tribally Controlled Colleges and Universities (TCCUs)

    o   Alaska Native and Native Hawaiian Serving Institutions

    o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

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

    For-Profit Organizations

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

    Governments

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

    Other

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

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are  eligible to apply.
    Non-domestic (non-U.S.) components of U.S. Organizations are  eligible to apply.
    Foreign components, as defined in the NIH Grants Policy Statement, are  allowed.

    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.
    • o   NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.  Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

    Eligible Individuals (Program Director/Principal Investigator)

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

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

    This program requires the full collaboration of the extramural PD/PI of the applicant institution and the intramural investigator(s).  The multiple PD/PI model is allowed, but not required; however, applications must include at least one NCATS intramural scientist as a collaborator. 

    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, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the 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:

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

    Page Limitations

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

    Instructions for Application Submission

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

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

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

    SF424(R&R) Other Project Information

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

    Other Attachments: 

    The following attachments must be included, as applicable.

    Collaboration Plan:

    Applications must include a Collaboration Plan, describing how the proposed collaboration will be maintained throughout the duration of the award. 

    The following areas should be addressed:

    • Organizational structure
    • Management plan detailing how existing resources, including the 3-D Bioprinting Laboratory at NCATS will be utilized
    • Planned interactions and responsibilities of key personnel
    • Clear and well described advantage to bringing the intramural and extramural investigators together in a collaborative partnership
    • Description of how research teams will communicate (e.g., videocast, web meeting, etc.)
    • Description of any pre-existing intellectual property

    The filename "Collaboration Plan-PI-NAME.pdf" should be used, must not exceed 50 characters, and will be reflected in the final image bookmarking for easy access by reviewers.  The Collaboration Plan is limited to 5 pages. Applications that do not include the Collaboration Plan will be considered incomplete and will not be reviewed.

    Milestone Plan

    Applications must include a Milestone Plan. The Milestone plan should:

    • Provide detailed quantitative criteria by which milestone achievement will be assessed.
    • Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
    • Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.
    • A timeline (Gantt chart) including milestones is required for all studies. Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success.

    The filename "Milestone Plan-PI-NAME.pdf" should be used, must not exceed 50 characters, and will be reflected in the final image bookmarking for easy access by reviewers.  The Milestone Plan is limited to 3 pages.  Applications that do not include the Milestone Plan will be considered incomplete and will not be reviewed.

    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 Grantee Costs

    Extramural costs may include such items as salary support for the extramural PD/PI and staff at the applicant organization, supplies, laboratory animals, data analysis, and other allowable costs for work performed at the (extramural) applicant organization, as well as travel costs for the extramural investigator(s). 

    • 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 Investigator Costs

    The requests by NIH intramural scientists will be limited to the incremental costs required for participation.  Intramural investigator costs may include salary for contract staff to be specifically hired under a temporary appointment for the project, consultant costs, supplies, and other items typically listed under Other Expenses.  Budget requests from the NIH intramural program may 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 costs).  Although the budget request may not include salary support for such individuals, it should indicate person months for any key personnel.  Resources required need to be determined before the research protocol can be approved by the respective NIH Institute/Center.  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 intramural investigator's 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.

    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.

    Additional Guidance on Budget Preparation

    The project will initially focus on transfer of protocols for biofabrication of skin disease tissue constructs and corresponding assays to NCATS, and for development of high-density screening platforms on microplates seeded with the skin disease tissue constructs. This work will be primarily performed at the NCATS 3-D Bioprinting Laboratory. Once the screen is completed and hits are identified, extramural investigators will be provided with the compounds and perform validation of hits identified in the screen in their laboratories. 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:

    Letters of Support: 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 3-D Bioprinting Laboratory will be able to accommodate the proposed research and that the NCATS intramural scientist will be able to collaborate on the project. Applications submitted without this letter of support will be considered incomplete and will not be reviewed.

    This collaborative translational research between NCATS intramural scientists and extramural investigators will involve either a Cooperative Research and Development Agreement (CRADA) or a Research Collaboration Agreement (RCA), which will need to be executed for projects deemed scientifically meritorious by peer review. NCATS will provide CRADA or RCA template documents to help streamline the interaction between NCATS intramural scientists and extramural investigators. These template agreements can be found on https://ncats.nih.gov/alliances/forms.  Questions regarding any of these agreements can be referred to the NCATS Office of Strategic Alliances at NCATSPartnerships@mail.nih.gov.  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 or RCA will need to be executed after the application has been identified for funding. While the CRADA or RCA 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/RCA should be included in the application. Failure to include this statement could result in delays should the application be identified for funding.

    Finally, letter(s) 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, with the following modification:

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

    Appendix:

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

    PHS Human Subjects and Clinical Trials Information

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    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. 

    Foreign Institutions

    Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

    3. Unique Entity Identifier and System for Award Management (SAM)

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

    4. Submission Dates and Times

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

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

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

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

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

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

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

    7. Other Submission Requirements and Information

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

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

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

    Important reminders:

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

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

    See more tips for avoiding common errors.

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

    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.

    For this particular announcement, note the following:

    This U18 grant supports development of novel biofabricated 3-D skin disease tissue models for drug screening that have the potential to provide evidence of success for utilization of biofabricated 3-D models for drug screening. The U18 grant application need not have substantial preliminary data in support of a fully-developed 3-D biofabricated skin disease model and corresponding assay(s) in a minim 6-well format. Accordingly, reviewers will emphasize the readiness of the model for adaption to a high throughput drug screening platform, the level of innovation, and the potential to significantly advance development of therapies for a particular skin disease.

     
    Overall Impact

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

    Scored Review Criteria

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

    Significance

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

    Specific to this FOA:

    • ·    Are the proposed model and associated assay of high physiological and pharmacological relevance to the problem that is to be addressed?
    • ·    What is the likelihood that the proposed approaches will have relevance for and/or inform development of novel 3-D bio fabricated models and drug screening platforms beyond the primary disease focus of this application?
    Investigator(s)

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

    Specific to this FOA:

    • ·    Has the PD/PI or investigative team previously demonstrated the ability to successfully participate in, or lead one or more complex projects?
    • ·    Does the PD/PI have experience in working collaboratively with multi-disciplinary teams?
    Innovation

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

    Specific to this FOA:

    • ·    Will the proposed strategy/strategies improve the ability to adequately model disease in vitro and utilize the model to advance discovery and development on novel treatments?
    Approach

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

    Specific to this FOA:

    • ·    Are the proposed approaches state-of-the-art and scientifically justified?
    • ·    Are all the cell lines that will be utilized established and well-characterized?
    • ·    If control, patient-derived or genetically engineered differentiated iPSC will be used, are all the differentiation protocols already established and tested for robustness and reproducibility?
    • ·    Can the protocols be readily scaled up to produce larger amounts of cells for HTS?
    • ·    Is the proposed assay for the screen physiologically relevant and HTS-compatible?
    • ·    Is (are) there a secondary assay(s) that will facilitate validation of hits following HTS?
    • ·    Does the application identify major technical risks, and are the proposed efforts to mitigate or address the risks clearly defined and feasible?
    • ·    Is the Collaboration Plan well defined with identifiable responsibilities for the NIH intramural investigator and the extramural applicant?
    • ·    Is a plan for management of the collaboration clearly presented, with well-defined descriptions of what each participant proposes to provide to the collaborative partnership?
    • ·    Is there a clear and well described advantage to bringing the intramural and extramural investigators together in a collaborative partnership?
    • ·    Are the listed milestones appropriate for the overall goals of the project?
    • ·    How well do the milestones address the specific aims of the project?
    • ·    Are the milestones feasible, well developed, and quantifiable with regard to the specific aims?
    • ·    Are quantifiable go/no go criteria included?
    • ·    Are the critical decision points and timelines appropriate?

    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?  

    Environment

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

    Additional Review Criteria

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

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the  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.

    Biohazards

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

    Resubmissions

    Not Applicable.

    Renewals

    Not Applicable.

    Revisions

    Not Applicable.

    Additional Review Considerations

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

    Applications from Foreign Organizations

    Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

    Select Agent Research

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

    Resource Sharing Plans

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

    Authentication of Key Biological and/or Chemical Resources:

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

    Budget and Period of Support

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

    2. Review and Selection Process

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

    As part of the scientific peer review, all applications:

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

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

    Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NCATS Advisory Council 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.
    • Compliance with resource sharing policies.
    • Likelihood of effective collaboration between the PD(s)/PI(s) of the applicant institution(s) and the NIH intramural investigators(s).
    • Utilization of unique opportunities available at the NCATS.
    3. Anticipated Announcement and Award Dates

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

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

    Section VI. Award Administration Information
    1. Award Notices

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

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

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

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

    2. Administrative and National Policy Requirements

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

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

    For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    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. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.      

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

    • Defining objectives and approaches, and planning, conducting, analyzing and publishing results, interpretations, and conclusions of their studies.
    • Identifying specific milestones that will be achieved during the project period.
    • Participating in the overall coordination of research efforts, including collaboration and consultation with NIH investigators, and the sharing of information, data, and research materials.

    Publications

    The Program Director/Principal Investigator (PD/PI) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD/PI and Project Leaders are requested to submit manuscripts to the NIH Project Scientist within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the Principal Investigator and appropriate Project Leaders and will require appropriate acknowledgement of NIH support. Timely publication of major findings is expected.

    Intellectual Property

    The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.

    Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project. The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act). Awardees will retain custody of and have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

    NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    The NIH intramural scientist is expected to have primary responsibility for a substantial portion of the proposed research and provide advice and technical assistance as needed.  The NIH intramural scientist will also participate 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.  The NIH intramural scientist is subject to the same publication/authorship policies as the official NIH publication policy.

    The NIH Program Officer will have substantial involvement in the study and will be responsible for the normal scientific and programmatic stewardship of the award.  The Program Officer will have decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees.

    The NIH reserves the right to phase out or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable protocol, (b) substantial shortfall in subject recruitment, consortium participation and collaboration with other awardees, (c) substantive changes in the agreed-upon methodologies and tools with which NIH cannot concur, (d) human subject ethical issues that may dictate a premature termination, or (e) results that substantially diminish the scientific value of study continuation.

    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. Awardees will participate in monthly calls with the NIH and semi-annual meetings. 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 3-D Bioprinting Laboratory unique resources were utilized and the new intramural-extramural partnerships that developed.  This will be evaluated by the program official/IC program director.

    Performance Requirements:

    • Meeting yearly milestones as defined by extramural and intramural investigators and NIH program at the time of award.
    • Working with, cooperatively interacting with, and actively seeking input from NIH.
    • Sharing data and biological specimens with the broader scientific community, using established data sharing guidelines.
    • Attending semi-annual in-person meetings.

    Dispute Resolution:

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the awardee, and 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.

    T&C Inclusions and Modifications

    The Terms and Conditions of Award will include references to the currently approved versions of the Collaboration Plan and the Sharing Plans for Resources and Data.  Before the initial award is made, NIH and the awardees may negotiate changes or additions to the versions of these plans in the application.  Future changes or additions to these plans may be developed by the NIH and the PD(s)/PI(s) and negotiated with the awardee.  Changes will be documented by an exchange of correspondence and the updated plans will become part of the Terms and Conditions of a revised Notice of Award.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

    A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

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

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Dobrila D. Rudnicki, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-594-2080
    Email: dobrila.rudnicki@nih.gov

    Danilo A. Tagle, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-594-8064
    Email: danilo.tagle@nih.gov

    Intramural Contacts:

    Anton Simeonov, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-217-5721
    Email: asimeono@mail.nih.gov

    Marc Ferrer, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-217-5722
    Email: marc.ferrer@nih.gov

    Peer Review Contact(s)

    Carol Lambert, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-435-0814
    Email: lambert@mail.nih.gov

    Financial/Grants Management Contact(s)

    Sarisa Kowl
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-594-1921
    Email: kowls@mail.nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

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

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.