Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)

Funding Opportunity Title

Genetic Engineering Technologies for HIV Cure Research (U19 Clinical Trial Optional)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-AI-18-058

Companion Funding Opportunity

None

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

93.855, 93.242  

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to apply genetic engineering technologies to HIV-1 cure research.  Gene- and/or cell-based approaches are sought that can achieve long-term remission of HIV-1 in the absence of antiretroviral treatment or complete elimination of HIV-1Applications are expected to include basic science/preclinical research as well as translational activities such as test-of-concept studies in animal models or human subjects and must be designed as collaborative efforts between academia and the private sector.

Key Dates

 

Posted Date

November 29, 2018

Open Date (Earliest Submission Date)

February 11, 2019

Letter of Intent Due Date(s)

February 11, 2019

Application Due Date(s)

Only accepting applications for the AIDS Application Due Dates listed below.

AIDS Application Due Date(s)

March 11, 2019, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on 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.

Scientific Merit Review

 July 2019

Advisory Council Review

 October 2019

Earliest Start Date

 December 2019

Expiration Date

March 12, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) 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. 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 Funding Opportunity Announcement (FOA) is to apply genetic engineering technologies to HIV-1 cure research.  Gene- and/or cell-based approaches are sought that can achieve long-term remission of HIV-1 in the absence of antiretroviral treatment or complete elimination of HIV-1.  Applications are expected to include basic science/preclinical research as well as translational activities such as test-of-concept studies in animal models or human subjects and must be designed as collaborative efforts between academia and the private sector.

     
    Background

    Thirty years of HIV-1 drug discovery and development have yielded potent combination antiretroviral drug regimens that successfully target viral enzymes and entry.  Improvements with respect to pill burden, toxicities, and drug half-life continue to be made.  However, HIV-1 is suppressed rather than eliminated by current small molecule inhibitors.  Suppression does not eliminate underlying features of the infection such as inflammation and leaves the infected person vulnerable to virus rebound if treatment is interrupted.

    Much has been learned about the virus and its interactions with the host since the beginning of the epidemic.  New viral and host targets have been identified that can serve as the basis for genetic interventions to suppress HIV-1 replication and reduce the size of the reservoir of latently infected cells.  In addition, some genetic engineering approaches harness the power of the immune system and offer the possibilities of specific delivery and even surveillance.

    There are challenges to be addressed by research before the new field of genetic engineering can contribute successfully to the treatment or cure of the wide variety of diseases amenable to gene-based interventions.  Examples of challenges for the field include:  low efficiency of in vivo delivery, specificity of targeting, immunogenicity of viral vectors and transgenes, the regulation of transgene expression, animal models that predict side effects and efficacy in humans, and development of resistance.  For HIV-1 approaches, there are additional challenges, including:  the heterogeneity of target HIV-1 sequences, particularly for nuclease-based technologies; the wide distribution of latently infected cells in the body; and a low frequency of target cells in drug suppressed animal models or human subjects.

    Research Objective and Scope

    The goal of this FOA is to support multiple research projects that when integrated sustain a single unifying research strategy using genetic engineering technologies to achieve long-term HIV-1 remission in the absence of antiretroviral treatment or elimination of HIV-1.  Ex vivo and in vivo gene modification approaches are allowed.

    Examples of research of interest include, but are not limited to:

    • Elimination or inactivation of HIV-1 provirus using genome- or epigenome-editing technologies.
    • Gene modification to render cells resistant to infection and/or better able to eliminate HIV- infected cells.  Examples of cell sources include but are not limited to:  T cells, NK cells, blood stem or progenitor cells, and novel cell sources such as induced pluripotent stem cells (iPSCs).
    • Delivery strategies, using viral or non-viral vectors or physical delivery methods to target modified cells, editing moieties, or therapeutic moieties to HIV-infected cells or tissues where persistently or latently infected cells reside.
    • Combination studies that include one required cell or gene therapy modality plus a drug, biologic, or other gene therapy modality.  Examples of drugs or biologics that could be combined with a cell or gene therapy include:  cytokines, monoclonal antibodies, a novel conditioning agent, an immunosuppressant, a latency reversing agent.
    • Methods to enhance transplantation and engraftment, or minimize rejection, of modified cells as part of an HIV-targeted transplantation strategy.  For example, this could include strategies to improve in vivo expansion, selection, persistence, or distribution of modified cells.
    • Test-of-concept studies in animals.  These studies could include efficacy studies in small animals on suppressive antiretroviral therapy, assessment of safety, immunogenicity, and resistance development.  Animal studies could use conventional or humanized mice or non-human primates.
    • Small scale test-of-concept clinical trials (feasibility or safety; ≤30 subjects):  optional.

    IND-enabling studies in animals (safety and/or toxicology) will not be supported under this FOA.

    NIMH will co-fund applications which contain projects or cores of interest to their mission.  Examples of areas of interest to the NIMH include, but are not limited to, the following:

    • Targeting of gene- or cell-based therapies to compartments of the CNS that harbor latent or persistent HIV;
    • Efficacy and/or toxicity of gene- or cell-based therapies in CNS compartments, as explored in test-of-concept studies in animals or humans.

    Applications proposing research in the areas listed below will be considered non-responsive and will not be reviewed:

    • Vaccines.
    • CCR5 as the sole target.
    • Transplantation research that is not an integral part of the HIV cure approach being developed under the FOA.
    • Clinical trials that are ready for implementation at the time of award without further basic or preclinical research.
    • Test-of-concept clinical trials conducted at international sites and/or not meeting the definition of size specified in this FOA.
    • Applications that focus exclusively on neuroAIDS.
    • Applications that fall exclusively within the mission of NIMH.

    Applications not designed as collaborative partnerships between academia and the private sector will be considered non-responsive and will not be reviewed.

    Applications proposing less than three or more than four Research Projects will be considered non-responsive and will not be reviewed.

    Partnerships

    Applications must include a collaborative partnership between academia and the private sector.  The term “private sector” comprises large and small organizations, domestic and foreign organizations, nonprofit and for-profit organizations.  Examples of private sector partners appropriate to this FOA include, but are not limited to, biotechnology, pharmaceutical, bioengineering, stem cell, and chemical companies.  The private sector partner must: propose a research plan that contributes intellectually to the overall goals and objectives of the program, contribute expertise and/or resources not generally available in academia, and have a record of past successes moving concepts to practical applications. 

    Translational studies

    This FOA will support test-of-concept studies in animals and/or human subjects.  Such studies must be directly linked to the basic research and/or preclinical development performed under the award.  If proposed, clinical trials must be conducted within the United States (U.S.), may not exceed 30 subjects, and must be carried out under an IND unless not required by the FDA.  Applicants are responsible for naming the party/institution who will serve as the IND holder; the NIH funding component(s) will not hold the IND.  If proposed, clinical trials must be initiated by the fourth year of the award.

    Translational studies are not expected to provide definitive, powered statistical assessments of the concept or strategy being evaluated, but should provide an early indication of whether the concept is safe and worthy of being pursued further on a larger scale.

    Program Structure

    Each application should include the following components:

    Administrative Core

    This core will provide the management, coordination, and supervision of both the scientific and fiscal aspects of the overall program.

    Research Projects

    Each application must include a minimum of three interrelated individual Research Projects. At least one Research Project Lead must be from the private sector, and at least one Research Project Lead must be from academia.  If proposed, clinical trials must be located within a project, not a core.  Research plan(s) for private sector Research Projects may be applied in nature rather than hypothesis-driven.

    Science Cores (Optional)

    An application may include development and maintenance of one or more Science Core(s) as resources and/or facilities that are essential for the activities of two or more Research Projects. Science Cores are intended to only serve the needs of project researchers.

    Additional Information

    Awardees will be asked to participate in a mid-year teleconference and an annual face-to-face meeting with NIH staff and a Scientific Advisory Board (SAB).  The purpose of the call and meeting is to review progress, plan and design research activities, and establish priorities. 

    In securing services and common resources to support the needs of the program, it is expected that

    applicants will leverage existing government-funded resources and/or programs whenever possible.  Examples include, but are not limited to:

    • Centers for AIDS Research (CFAR, NIAID);
    • Production Assistance for Cellular Therapies (PACT, NHLBI);
    • Clinical and Translational Science Awards (CTSA, NCATS);
    • Blood and Marrow Transplant Clinical Trials Network (BMT CTN, NHLBI/NCI) and the AIDS Clinical Trials Group (ACTG, NIAID).

    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?

    Optional: Accepting applications that either propose or do not propose clinical trial(s)

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIAID and partner component intend to commit an estimated total of $5 million to fund 2 awards.

    Award Budget

    Application budgets are limited to $1.75 million in direct costs per year. Budgets should reflect the actual needs of the proposed project.

    Award Project Period

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

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

    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
    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.
    • 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.

    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 or an institutional system-to-system solution. A button to apply using ASSIST is 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

    Bruce Sundstrom, Ph.D.
    Telephone: 240-669-5045
    Email: sundstromj@niaid.nih.gov

    Page Limitations

    Available Component Types

    Research Strategy/Program Plan Page Limits

    Overall

    12 pages

    Admin Core (Use for Administrative Core)

    6 pages

    Core (Use for all Science Cores)

    6 pages each

    Project (Use for Research Projects)

    12 pages each

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

    Instructions for the Submission of Multi-Component Applications

    The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

    The application should consist of the following components:

    • Overall:  required
    • Administrative Core:  1 required
    • Science Cores:  optional
    • Research Projects:  3 required, maximum 4
    Overall Component

    When preparing your application, use Component Type ‘Overall’.

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

    SF424 (R&R) Cover (Overall)

    Complete entire form.

    PHS 398 Cover Page Supplement  (Overall)

    Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

    Research & Related Other Project Information (Overall)

    Follow standard instructions.

    Project/Performance Site Location(s) (Overall)

    Enter primary site only.

    A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

    Research & Related Senior/Key Person Profile (Overall)

    Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

    A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

    Budget (Overall)

    The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.  

    A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

    PHS 398 Research Plan (Overall)

    Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed overall program.  Concisely describe the concept or concepts to be tested.   

    Research Strategy:   The overall application should be composed of scientifically meritorious individual projects related to a common theme, with each project proposing research that addresses an aspect of the overall program.  Projects should be well integrated into the overall program and form a synergistic, scientifically compelling whole.  The research strategy section provides the PD/PI with an opportunity to demonstrate the conceptual wholeness of the overall program by stating the general problem area and laying out a broad strategy and timeline for addressing the research goals.

    Include a discussion of how the proposed gene- and/or cell-based strategy represents an improvement over current antiretroviral drug treatments for HIV-1 and how it meets the definition of a cure strategy, i.e., a strategy that can achieve either long-term remission in the absence of antiretroviral treatment or elimination of HIV-1.  If the strategy is designed to effect long-term remission, discuss the possible duration of virus suppression expected and how often (months, years?) the treatment would need to be given.  If combination studies are proposed, provide a rationale for choosing the modality(ies) to be combined with the gene- and/or cell-based therapy.

    Briefly discuss each individual research project and core with respect to its place in the scheme of the overall research program.  Include a graphic illustrating the relationship of the various projects to one another and their place in the overall program.  Describe the private sector involvement, the unique expertise and resources it provides, and how it will be integrated into and benefit the proposed program.  While hard milestones are not required, the application should identify significant research outcomes, with timelines, to allow assessment of the program's progress toward its stated goals throughout the program lifetime.

    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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Overall)

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    This FOA will only accept delayed onset studies for all proposed potential clinical trials.

    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 (Overall)

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

    Administrative Core

    When preparing your application, use Component Type ‘Admin Core.’

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

    SF424 (R&R) Cover (Administrative Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Administrative Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Administrative Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Administrative Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Administrative Core)
    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    • For institutions/organizations proposing a single PD/PI, the PD/PI must serve as the Administrative Core Lead. For institutions/organizations proposing multiple PD(s)/PI(s), the contact PD/PI must serve as the Administrative Core Lead.  Include the following information in the biographical sketch of the PD/PI to highlight previous experience in the following areas: providing leadership and guidance to scientific teams, creating an infrastructure that promotes cross-discipline interactions, and providing oversight and governance over fiscal and resource management.   
    Budget (Administrative Core)

    Budget forms appropriate for the specific component will be included in the application package.

    • Include expenses for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications related to the program, and communication expenses.
    • Include expenses related to the travel of external experts [Scientific Advisory Board (SAB) members] and the Administrative Core Lead to the annual meeting of the awardees in the Administrative Core budget.  Assume travel for 2 unnamed SAB members and the Core Lead or their representative(s) to attend a 1-day meeting per annum in Rockville MD.

    Note:  No additional travel funds may be requested for attendance of scientific meetings or conferences other than the mandatory annual program meeting.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Administrative Core)

    Specific Aims: List in priority order the broad, long-range objectives and goals of the core.   

    Research Strategy: Discuss how this core will function as an administrative resource to the grant, providing for the management, coordination, and supervision of both the scientific and fiscal aspects of the overall program.  Provide an administrative plan that describes how the following will be managed by the core:  internal data dissemination, including the tools that are available to facilitate communication and coordination among members of the team and program; presentation and publication policy for data generated by the overall and individual projects; tracking of project and core progress; meeting NIH reporting requirements related to research and clinical trials (if applicable); and internal dispute resolution.  When applicable, describe how existing government-funded resources and/or programs will be leveraged to secure the services and common resources needed to support the program.

    Describe how the Administrative Core will establish and maintain a strong collaborative environment. Address institutional support for intellectual property management and a contingency plan for replacing the PD/PI(s), if needed.  

    Describe the internal procedures that will be developed for evaluating and responding to recommendations from the Scientific Advisory Board (SAB).  The SAB will be constituted post award from recommendations put forward from grantees awarded under this FOA.  Do not name or contact potential SAB members.   

    Letters of Support:  In furtherance of successfully achieving the overall program goals, PD(s)/PI(s) are encouraged to provide letters of support documenting consensus with any potential partners regarding intellectual property, data sharing, and other legal matters that may arise during the period of the award. Do not request letters of support from potential SAB members.

    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 items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Administrative Core)

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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

    Science Core (Optional)

    When preparing your application, use Component Type ‘Core.’

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

    SF424 (R&R) Cover (Science Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Science Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Science Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Facilities & Other Resources:  Include an attachment entitled "Facilities & Other Resources" to provide information on resources available for the Science Core(s).  If there are multiple performance sites, describe the resources available at each site.

    Equipment:  Include an attachment entitled "Equipment" to provide information on equipment available for the Science Core(s).  If there are multiple performance sites, describe equipment available at each site.  Describe any special equipment available to be used for working with biohazards or other potentially dangerous substances.

    Project /Performance Site Location(s) (Science Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Science Core)
    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   
    Budget (Science Core)

    Budget forms appropriate for the specific component will be included in the application package.

    • Include expenses related to participation of Science Core personnel in the annual meeting of the awardees in the budget of the respective Science Core.  Assume a 1-day meeting in Rockville, MD for the Core Lead or a representative per annum.

    Note:  No additional travel funds may be requested for attendance of scientific meetings or conferences other than the mandatory annual program meeting.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Science Core)

    Specific Aims:  List in priority order, the broad, long-range activities and services to be provided by the Science Core(s).  

    Research Strategy:  Use this section to describe how the proposed core activities will contribute to meeting the goals and objectives of the research proposed in the application and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims.

    Clearly describe the skills, techniques, resources, and quality control process(es) for the services the core will provide.  Each Science Core must serve at least two individual Research Projects; indicate the specific Research Projects to be served and how they will be served by each Science Core.  In addition, indicate the relevance of the Science Core to the primary theme of the application.  Explain how requests for services will be prioritized and coordinated.  In a clearly labeled section provide timelines for the proposed core services.  

    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 items are allowed in the Appendix.  Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Science Core)

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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.

    Research Project

    When preparing your application, use Component Type ‘Project.’

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

    SF424 (R&R) Cover (Research Project)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Research Project)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Research Project)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Facilities & Other Resources:  For each individual Research Project, include an attachment entitled "Facilities & Other Resources" to provide information on resources available for that project.  If there are multiple performance sites, describe the resources available at each site.

    Equipment:  For each individual Research Project, include an attachment entitled "Equipment" to provide information on equipment available for that project.  If there are multiple performance sites, describe equipment available at each site.  Describe any special equipment available to be used for working with biohazards or other potentially dangerous substances.

    Project /Performance Site Location(s) (Research Project)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Research Project)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   
    Budget (Research Project)

    Budget forms appropriate for the specific component will be included in the application package.

    • Include expenses related to participation of project personnel in the annual meeting in the budget of the respective individual research project.  Assume a 1-day meeting in Rockville MD for the Project Lead or a representative per annum.
    • If a clinical trial is proposed, include all budget amounts for conducting the trial, including full regulatory support, and site monitoring.

    Note:  Private partner-led Research Projects may budget in the same categories as academic-led Research Projects.

    Note:  No additional travel funds may be requested for attendance of scientific meetings or conferences other than the mandatory annual program meeting.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Research Project)

    Specific Aims:  List specific aims in priority order.  

    Research Strategy: 

    Academic partner-led Research Project(s):

    Use this section to describe how the research of the individual Research Project will contribute to the overall goals and objectives of the proposed program and how the individual Research Project relates to the other projects and cores within the application.  Concisely describe the hypothesis or hypotheses to be tested.  Describe the research design, methodologies, and analyses to be used to carry out the specific aims.  Describe any novel concepts, approaches, or tools to be utilized.

    Private partner-led Research Project(s):

    Use this section to describe the unique nature and strengths to be provided by the private sector partner(s).  Indicate how the private sector project(s) contributes materially and intellectually to the program.  Include a description of the partner's past successes moving concepts forward to practical applications.  Describe the research design, methodologies, and analyses to be used to carry out the specific aims.  Describe any novel concepts, approaches, or tools to be utilized.

    Test-of-concept studies in animals or human subjects:  include a brief description of the study, including elements such as study design, endpoints, and rationale for choice of the animal model or study population.  Since only small test-of-concept clinical trials will be permitted (≤30 subjects) and are expected to be based on research results that cannot be anticipated at the time of application submission, only delayed onset study records will be accepted.  Do not submit a detailed clinical trial study record.

    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 items are allowed in the Appendix.  Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Research Project )

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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 modification:

    This FOA will only accept delayed onset studies for all proposed potential clinical trials.

    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.

    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) using ASSIST or other electronic submission systems. 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.

    For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

    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) and component Project Leads 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.

    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 (SAM). 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.

    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 - Overall

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the program 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 program proposed).

    Review Criteria - Overall

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

    Specific to this FOA

    • Is the overall program scientifically compelling? 
    • Does the proposed strategy have the potential to lead to a HIV-1 cure?
    • Is the proposed strategy an improvement over current antiretroviral therapy and does it meet the definition of a cure strategy?
    • Did the applicant address the length of time their approach might be effective if less than permanent?
    • If proposed, are combination studies scientifically sound and is the rationale for choosing the modality(ies) to be combined with the gene- and/or cell-based therapy appropriately justified?
    • Is the potential for synergy among the program components apparent?
    • Has a multidisciplinary team with the appropriate and complementary expertise required to accomplish the proposed research program been assembled? 
    • Do/does the PD(s)/PI(s) have the leadership and scientific capabilities to develop an integrated and focused research program?  Will the PD(s)/PI(s) devote adequate time and effort to the program?
    • Is each project and core well-integrated into the scheme of the overall program?
    • Are significant research outcomes, with timelines, identified against which progress can be measured?
    Overall Impact - Research Project  

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

    Scored Review Criteria - Research Project

    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?

    In addition, for applications involving clinical trials

    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?

    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

    Will the individual Project Lead devote adequate time and effort to the project?

    In addition, for applications involving clinical trials

    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?

    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?

    In addition, for applications involving clinical trials

    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?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have 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?

    In addition, for applications involving clinical trials

    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?

    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?

    In addition, for applications involving clinical trials

    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?

    Overall Impact – Administrative Core, Science Core(s)

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core 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 core proposed).

    Review Criteria – Administrative Core, Science Core(s)

    Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and will give an overall impact score for each Core but will not give separate scores for these items.

    Administrative Core
    • Is the administrative and organizational structure clearly defined and is it appropriate and adequate to accomplish the objectives of the overall program?
    • Is the management plan for fiscal accountability and communication appropriate to facilitate attainment of the objectives of the proposed overall program?
    • Are plans to leverage existing Government funded resources included for the benefit of the overall program?
    • Are the experience, level of commitment, and availability of the Administrative Core Lead adequate to manage the overall program?
    • Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the overall program appropriate?
     
    Science Core(s) (if applicable)
    • Is (Are) the proposed Science Core(s) justified and relevant to the theme of the overall program?
    • Is adequate justification provided that each Science Core will support at least two individual Research Projects?
    • Are the proposed personnel appropriate to lead and staff the core?  Are the experience, level of commitment, and availability of the Core Lead adequate?
    • Are the relevant facilities and/or services provided appropriate for the activities proposed (including procedures, techniques, quality control), and are the criteria for prioritizing requests for services appropriate?
    Additional Review Criteria - Overall, Research Projects, and Cores

    As applicable for the project/core 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.

    • Did the private sector partner propose a research plan that contributes materially and intellectually to the overall goals and objectives of the program, have the potential to contribute expertise/resources not generally available in academia, and have a record of past successes moving concepts to practical applications? 

    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.

    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 - Overall, Research Projects and Cores

    As applicable for the project/core 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 .


    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 National Institute of Allergy and Infectious Diseases 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 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. 

    ClinicalTrials.gov: 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 ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov/). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/  

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as 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 http://grants.nih.gov/grants/policy/hs/data_safety.htm 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 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 Part 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 for:

    • Planning, directing, and executing the proposed program in accordance with the proposed timeline;
    • Integrating and implementing the recommendations of the Scientific Advisory Board (SAB) into the activities of the program;
    • Prior to implementation of any clinical trial, demonstrating readiness with regard to the preclinical support for the study, the availability of funds to carry out the study, compliance with all applicable Federal, State, and Local regulatory requirements and with all applicable DHHS, NIH, and Institute/Center (IC)-specific policies and procedures for the conduct of clinical research; and a timeline consistent with completion of the study within the term of the award.
    • Submitting protocols for clinical trials, if any, for review and approval by the appropriate IC protocol review group. The review will include assessment of the scientific objectives, design, safety, ethics, and feasibility of proposed research protocols.
    • Communication with the NIH Project Scientist regarding the status of ongoing research, particularly in the case of clinical activity (enrollment, adverse events, interactions with the FDA, problems and resolution of same, changes in personnel, protocol amendments, etc.).

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

    • Participating in the design of activities;
    • Facilitating access to resources and information that otherwise might not be available to the awardee;
    • Advising on the management of the projects and technical performance;
    • Facilitating interactions between the awardee and other groups of importance to the awardee, for example, IC clinical trials networks, the FDA, pharmaceutical and/or biotechnology companies;
    • Providing guidance and oversight on compliance with Federal regulations related to human subjects research and IC policy on clinical research, and communicating in a timely manner information that might affect the safety of subjects in grant supported studies.

    Note:  an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

    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 PD(s)/PI(s) chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the 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)

    Sandra Bridges Gurgo, Ph.D.
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone: 301-496-8198
    Email: sbridges@mail.nih.gov

    Jeymohan Joseph, Ph.D.
    National Institute of Mental Health (NIMH)
    Telephone: 240-627-3869
    Email: jjeymoha@mail.nih.gov

    Peer Review Contact(s)

    Bruce Sundstrom, Ph.D.
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone: 240-669-5045
    Email: sundstromj@niaid.nih.gov

    Financial/Grants Management Contact(s)

    Raul Hernandez
    National Institute of Allergy and Infectious Diseases (NIAID)
    Telephone: 240-669-2957
    Email: raul.hernandez@nih.gov

    Rita Sisco
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-2805
    Email: siscor@mail.nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

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

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