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

Pilot Clinical Trials to Eliminate the Latent HIV Reservoir (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of RFA-AI-13-055

Related Notices

  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)

Funding Opportunity Announcement (FOA) Number

RFA-AI-16-012

Companion Funding Opportunity

None

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

93.855, 93.856, 93.242

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support pilot clinical trials that test intervention(s) aimed at eliminating cells that are latently-infected with HIV.  Trials supported by this FOA should include full integration with laboratory approaches to detect and measure the elimination of latently-infected cells in blood, cerebral spinal fluid, if appropriate, and tissue.

Key Dates
Posted Date

March 10, 2016

Open Date (Earliest Submission Date)

June 26 2016

Letter of Intent Due Date(s)

June 26, 2016

Application Due Date(s)

July 26, 2016, 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.

AIDS Application Due Date(s)

July 26, 2016, 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 these dates.

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

November 2016

Advisory Council Review

January 2017

Earliest Start Date

March 2017

Expiration Date

July 27, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

The purpose of this Funding Opportunity Announcement (FOA) is to support pilot clinical trials that test intervention(s) aimed at eliminating cells that are latently infected with HIV.  Trials supported by this FOA should include full integration with laboratory approaches to detect and measure the elimination of latently-infected cells in blood, cerebral spinal fluid, if appropriate, and tissue. 

Background

HIV infection can be effectively treated with modern medical management but individuals require lifelong therapy. Early in the course of HIV infection a pool of latently infected cells is established, some of which are extremely long-lived.  These cells contain integrated proviral DNA, some of which is replication competent. Integrated HIV provirus persists in latently infected cells and discontinuation of antiretroviral therapy leads to rapid virological rebound.  Several patients have been described with prolonged remission of HIV in the absence of antiretroviral therapy and this has sparked renewed interest in understanding the events involved in HIV latency and persistence with the goal of eliminating the latent reservoir. Prior efforts have focused on the reversal of latency; it was hoped that the reversal of latency would cause the death of the latently infected cells by either cytopathic effects of HIV itself or by immune-mediated clearance. It is now clear that reversal of latency is not sufficient to destroy all the cells containing the virus. 

A growing understanding of HIV persistence has identified new mechanisms that might be employed to reduce or eliminate the latent reservoir. For example, it has been suggested that markers of immune exhaustion might identify cells that are latently infected with HIV. These cells might be targets of further intervention.  In addition, intracellular signaling processes involved in various steps of the viral life cycle may have utility in reducing the latent HIV reservoir. The understanding that some latently infected T cells, perhaps predominantly from a specific compartment of central memory T cells, undergo clonal expansion might offer an additional pathway to explore. Immunological approaches, including the use of both cell and antibody-based therapeutics, as well as processes involving regulatory T cells have advanced enough so that novel interventions can now be investigated. 

Significant questions include, but are not limited to:   

  • What are the best interventions to enhance innate and adaptive immune responses with the goal of eliminating latently-infected cells?
  • Is an activation step required for elimination of the HIV reservoir, or can latently-infected cells be targeted directly? 
  • Are there steps in the pathway to maintaining latency and persistence that can be targeted, resulting in the death of latently-infected cells? 
  • Does interruption of mechanisms that allow HIV in latently-infected cells to escape immune recognition lead to increased elimination of these cells?
Research Objectives and Examples of Research Strategies

This FOA solicits applications to specifically propose interventions that will eliminate latently- infected cells containing replication competent HIV provirus. Interventions might include drugs, biologics, vaccines and/or other interventions. An activation step may or may not be required; some approaches might directly target cells that do not express HIV proteins and are therefore immunologically silent.  The objective of this FOA is to facilitate the translation of basic research findings into novel approaches and mechanistic clinical studies that will enhance the elimination of cells containing replication competent HIV in HIV-infected adults on effective long-term suppressive therapy. These trials may inform understanding of the cell types, location, and numbers of latently infected cells; however applications that deal only with the detection and measurement of latently infected cells would not be responsive. 

The field still lacks a consensus on the best methods to reliably detect and quantify the amount of replication-competent HIV provirus inside host/reservoir cells. This field is rapidly evolving, and applicants must incorporate state-of-the-art measurements in response to this FOA. Novel methodologies and assays designed to assess the effects of specific interventions are encouraged but must be used in parallel with other laboratory approach(es) that measure elimination of latently infected cells. All responsive applications must contain preliminary data demonstrating that latently infected cells can be eliminated by the proposed approach(es). 

Specific Areas of Research Interest

Novel therapeutic vaccines and other immunological approaches that harness and enhance the patient’s immune response are of interest, including, but not limited to:

  • Interventions that target intracellular mechanisms that maintain latency or promote apoptosis of cells containing latent HIV
  • Immunological mechanisms employing broadly neutralizing or non-neutralizing antibody to boost antibody-dependent cytotoxicity or antibody-dependent cellular phagocytosis
  • Gene editing or genetic engineering approaches, either with or without an activation step
  • Strategies that interrupt latency or promote clearance of latently-infected cells. 
  • Cell-based strategies
  • Strategies that reverse T cell exhaustion
  • Therapeutic vaccines, including T cell-based vaccines that harness and enhance the individual’s immune response in order to target specific HIV targets or at latently-infected cells

Meritorious applications that include clinical studies to reduce the CNS and/or myeloid cell HIV reservoir by preventing translocation of cells containing replication competent HIV across the blood-brain barrier or elimination of cells within the central nervous system in HIV-infected adults on effective long-term suppressive therapy will be considered for co-funding by NIMH.

The following types of applications will be considered non-responsive, and will not be reviewed:

  • Trials proposing interventions that focus solely on reversing latency (activation), or on reservoir measurements without an elimination strategy
  • Trials proposing interventions that induce non-specific T-cell activation through general transcription activators
  • Applications that require the generation of preclinical data in order to support the hypothesis that the approach will eliminate latently-infected cells
  • Applications that do not justify the choice of endpoints and do not thoroughly describe experiments to support the approach and the assay(s) used to quantify a reduction in the size of the latent reservoir
  • Drug discovery and development programs
  • Applications that focus solely on the detection and measurement of latently infected cells
  • Trials intended to support a New Drug Application (NDA)
  • Research on approaches already under extensive investigation in the HIV field.
  • Trials conducted at clinical research sites outside of the United States. Foreign collaboration, however, is allowed.
  • Trials involving more than 2 clinical research sites
  • Studies performed only in animal models

This FOA will NOT support clinical trial planning activities, such as:

  • Development of study design
  • Identification of collaborators and enrollment site
  • Development of the clinical protocol and informed consent
  • Development of the statistical analysis plan
  • Development of the data management plan
  • Development of the Investigator’s brochure or Product Package Insert

Investigators seeking support for the planning and design of clinical trials should refer to the NIAID Clinical Trial Planning (R34) Grant FOA (PAR-13-150).

Each award made through this FOA will support one pilot interventional trial in HIV-infected adults on suppressive antiretroviral therapy.  Subjects selected for each study will have sustained undetectable plasma viral load levels below the limit of detection (less than 50 copies/ml) for a minimum of 2 years. Patients known to have been treated during acute infection may be an attractive population to study because of the more limited reservoir size and preserved immunological function. The trials will be conducted at no more than 2 clinical research sites in the U.S. and will involve a small number of total subjects (e.g., 30 subjects or fewer).

NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.  Clinical trials supported by this FOA will be hypothesis-driven and designed to investigate the impact of an intervention(s) with a proposed mechanism of action for the elimination of the latent HIV reservoir.  The expectation is that these trials will generate hypotheses that can be tested later in larger clinical trials.  Accordingly, state-of-the-art laboratory endpoints that quantify the reduction in the number of latently-infected cells caused by the intervention should be employed within the study design.  Improved assays for quantifying changes in the latent cell reservoir may soon be available and would be considered responsive. 

Implementation: 

This FOA may support activities related to the conduct of the clinical trial, including, but not limited to:

  • Training of study personnel related to the conduct of the trial
  • Enrollment and recruitment of study subjects
  • Data collection, management and quality control only for the trial
  • Laboratory work and data analysis
  • Study management and oversight
  • Establishment of committees to manage trial implementation activities
  • Preparation of the final study report
  • Other related post-enrollment activities
  • Regulatory activities to support the implementation of the trial

It is not expected that these exploratory trials will achieve statistical significance, but will instead support or refute hypothesized approaches to eliminate the HIV reservoir. 

All clinical trial planning activities must be completed by the time of application submission.  It is expected that investigators will implement the proposed trial within 9 months of receiving the award.

Other Requirements

Pilot clinical trials are subject to review and approval by the NIH Program Official and Medical Officer, the DAIDS Clinical Science Review Committee, and other necessary external advisors before opening to enrollment and when significantly amended.   While preparing applications for submission under this FOA, applicants are encouraged to review the NIAID Clinical Terms of Award and associated guidance documents, policies, and procedures under which the award will be made.  These include, for example:  http://www.niaid.nih.gov/researchfunding/sci/human/Pages/clinterm.aspx and the DAIDS Clinical Research Policies and Standard Procedures Documents that describe requirements for DAIDS-funded research. 

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.

Funds Available and Anticipated Number of Awards

The following NIH components intend to commit the following amounts in FY FY2017 to fund 2-3 awards:

NIAID, $4,000,000

NIMH, $750,000

Award Budget

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

Award Project Period

The scope of the proposed project should determine the project period.  The total project period may not exceed 5 years.

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • 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) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

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

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

2. Content and Form of Application Submission

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

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Peter R. Jackson
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5049
Email: pjackson@niaid.nih.gov 

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: The following items are required for this FOA, and must be included as separate PDF attachments.  Applications that lack any of these attachments will be considered incomplete and will not be peer-reviewed.

Clinical Protocol Synopsis

Name the PDF-formatted document "Clinical Protocol Synopsis.pdf".

The clinical protocol synopsis must include the following information:

  • Title
  • Participating Site(s)
  • Hypothesis
  • Intervention(s)
  • Study Design, including schema showing schedule of interventions, procedures and evaluations
  • Study population, including sample size and subject inclusion/exclusion criteria
  • Primary immunologic and virologic endpoints
  • Brief rationale for the trial, including justification for the selection endpoints and intervention(s)
  • Applications that lack the Clinical Protocol Synopsis will be considered non-responsive and will not be peer reviewed.

Milestone Plan

Name the PDF-formatted document “Milestone plan.pdf”.

Each trial supported by this FOA must have a milestone plan that includes milestone goals for implementing and, if needed, modifying the trial based on new information generated by the trial or the field. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. The milestones are subject to negotiation prior to award and will be incorporated into the terms of award. Continuation of funding for these trials will be based upon satisfactory progress in meeting negotiated milestones. 

This section must include:

  • If applicable, communication(s) with the FDA regarding the IND submission
  • Estimated date for readiness to submit protocol and Subject Informed Consent to  NIAID for review at the DAIDS Scientific Review Committee
  • Projected date of Recombinant DNA Advisory Committee (RAC) review, if applicable
  • Detailed recruitment plan with timeline for enrolling the first subject, and for enrolling 25%, 50% and 100% of the targeted study population, including a futility assessment if specified targets are not met
  • Dates planned for meetings of the independent data and safety monitoring committee overseeing the trial
  • Date by which site(s), pharmacy(ies) and laboratory(ies) will be ready to start trial 
  • Date by which data collection is expected to be complete
  • Date by which the data analyses is expected to be completed
  • Date of expected distribution of a final study report 

Regulatory Activities

Name the PDF-formatted document “Regulatory.pdf”.

NIAID reserves the right to specify:  1) whether an IND (Investigational New Drug) application should be submitted to the FDA; 2) who will serve as sponsor to hold the IND; and 3) the requirements for the establishment of a DSMB (Data Safety Monitoring Board)/SMC (Safety Monitoring Committee).

In most cases, it is expected that the grantee or designee will hold the IND rather than NIAID.

If the applicant proposes an eradication approach that would require input from the U.S. Food and Drug Administration, a regulatory strategy and plan for FDA submissions must be included.    If an IND submission is needed, applicants are expected to have received positive feedback from the FDA on the proposed clinical trial prior to the time that their U01 grant application is submitted to the NIH so that the trials can commence within 9 months of the award.  In most cases, NIAID will not hold the IND for these trials. Therefore, applicants must possess or hire appropriate regulatory support to manage regulatory submissions to the FDA if the approach requires FDA input.  If an IND is necessary, then applicants must state the name of the institution or company they propose to serve as the IND holder.

Applicants must also describe an approach for data management that is consistent with current FDA guidance, regulations for Electronic Signatures described in 21 CFR Part 11, and predicate rules set forth in the PHS Act.  Applicants are encouraged to also consider the FDA requirements for providing regulatory submissions in electronic format.  Limited information on both of these requirements can be found at the websites below: 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=11&showFR=1&subpartNode=21:1.0.1.1.8.3

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm153574.htm.

All communications with the FDA must be submitted for review as part of the application.  If a pre-IND meeting request is granted by the FDA, applicants must include the list of questions posed to the FDA and the official meeting minutes, if they are available.  Applicants who have requested an IND/IDE exemption must submit either: 

  • a copy of the letter that was sent to the FDA requesting an IND/IDE exemption for the proposed trial, and information about the status of the FDA’s review (e.g. decision pending as of XX date, queries received on XX date); OR
  • a copy of the FDA letter granting an IND/IDE exemption letter for the proposed trial

Evidence of permission to access proprietary/privileged information required to accomplish the study aims, if applicable

Name the PDF-formatted document “Permissions.pdf”.

If the application relies upon patentable ideas, trade secrets, privileged or confidential commercial information or study agents or materials that are not owned by the applicant, but are necessary for regulatory approval or for the trial itself, the applicant must include a letter of agreement from the collaborators stating willingness to supply these data and/or resources to the applicant for the proposed clinical trial.  Alternatively, a signed Material Transfer Agreement must be included in the application. 

Laboratory Methods for the Proposed Integrated HIV Provirus Assay   

Name the PDF-formatted document “Laboratory Assay.pdf”.  Applicants are urged to be succinct. 

The laboratory protocol for the assay to measure elimination of latently-infected cells must be provided.  Data to support the reliability of the assay, and validity for use as a surrogate marker of latent cell elimination must also be provided.  Investigators must adhere as closely as possible to NIAID’s policies when proposing endpoint assays that are for investigational-use only, and are not approved by the FDA nor validated by the International Conference on Harmonization (ICH) or U.S. Pharmacopeia.   Applicants must address plans for assuring compliance with Good Clinical Laboratory Practices (GCLP) and for performing proficiency assessments. If assay results will be used to determine participant eligibility for trials or treatment decisions during trials, address plans to ensure the relevant assays are CLIA compliant and performed in CLIA-certified laboratories.  For guidance, see:

http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Pages/reqUSLab.aspx

Complete Clinical Protocol and Subject Informed Consent Form

Name the PDF-formatted document “Clinical Protocol.pdf”.  Applicants are urged to be succinct. 

Investigators are referred to the following websites for guidance:

Trans-NIAID Clinical Research Toolkit website for templates and clinical protocol guidance.

http://www.niaid.nih.gov/labsandresources/resources/toolkit/Pages/default.aspx

SF424(R&R) Senior/Key Person Profile

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

PD(s)/PI(s) and other key person biosketches should describe expertise relevant to implementing a high-risk clinical trial. PD(s)/PI(s) should provide evidence that they have sufficient time to dedicate to this grant and the high-risk trial it supports. Early stage/new investigator biosketches should indicate relevant mentoring and support at their institution, as appropriate.  

Include biosketches for employee(s) who will assist the PD(s)/PI(s) in preparing for and implementing the clinical trial at the grantee’s clinical research site(s). A Study Coordinator and/or a Project Manager will assist the grant PD/PI in facilitating site readiness for the trial, communication between protocol team members, and in tracking study progress according to pre-set milestones. They should distribute written documentation of progress made in accomplishing the activities described in the milestone plan to all members of the protocol team as appropriate.

R&R or Modular Budget

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

Because all applications must include detailed scientific and operational plans, funding needs for the entire trial and data analysis period must also be included. Investigators must submit a complete, justified, individual budget for each year of support requested. All costs requested and all changes in budgets after the first year should be clearly identified and justified.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating site. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail along with supporting letters signed by individuals who have the authority to make fiduciary commitments on behalf of the institution (see Letters of Support section in the PHS 398 Research Plan below). These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget or as Estimated Project Funding.

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: The hypothesis(es), goals and expected outcome(s) of the trial should be concisely stated. Specific attention should be given to the rationale for the proposed intervention(s), including the hypothesized route or mechanism(s) of action that lead to the elimination of latently-infected cells.  The application should specify the primary endpoint(s) to be measured and provide justification for their inclusion. 

Research Strategy: The Research Strategy includes the Significance, Innovation and Approach sections. Provide an overview of the state of the science, current status and relevance of the trial, and a description of the clinical trial.  The Research Strategy should include:  

  • A clear hypothesis(es) stating the proposed mechanism by which the interventions or approaches will eliminate cells containing integrated HIV proviral DNA in HIV-infected individuals who are taking effective antiretroviral therapy (include preliminary data).
  • A description of and a rationale for the proposed study design with an emphasis on how the trial will clearly test the stated hypothesis(es).
  • A concise description of the overall strategy, methodology, and analyses to be used to accomplish the goals and specific aims of the trial, including a description of the assay(s) used to quantify a reduction in the size of the latent reservoir.  
  • A discussion of how the intervention will exert an effect (reduction and/or elimination) on cells and tissues that are believed to comprise the latent HIV reservoir.  Applicants should provide a rationale for how positive or negative results could provide meaningful information to advance the field.
  • A description of the study population and explanation of why it is an appropriate population to study the research question(s) posed.
  • A justification for the proposed sample sizes using either power calculations or non-statistically powered justifications.
  • A rationale as to why the proposed intervention is sufficiently novel to justify potential risks to subjects as well as the resources and effort required to implement the trial. 

Letters of Support: Provide all appropriate letters of support, including any letters necessary to demonstrate the support of laboratories and other collaborators.  If co-funding or in-kind support is planned from non-NIH sources (e.g. from drug supplier(s)), letter(s) outlining details of the commitment (e.g. type, amount and source of support), signed by a business official on organization letterhead, must be included. If NIH collaborators are substantially involved, document their Institute/Center’s concurrence with the proposed activities by including letters of support signed by the director of the Institute/Center.

If the application relies upon patentable ideas, trade secrets, privileged or confidential commercial information or study agents or materials that are not owned by the applicant, but are necessary for regulatory approval or for the trial itself, the applicant must include a letter of agreement from the collaborators stating willingness to supply these data and/or resources to the applicant for the proposed clinical trial.  Alternatively, a Material Transfer Agreement must be signed and included in the application.

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

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

Appendix:  Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Provide the following in the Appendix: The Investigator’s Brochure or Package Insert for the study product(s), if applicable.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

 Consultation with NIH Program Staff

Applicants are strongly encouraged to consult with NIH as plans for an application are being developed. Early contact provides an opportunity for NIH to discuss the program scope and goals, and to provide information and guidance on how to develop an appropriate milestone plan. Other aspects of an application that are unique to this program may also be discussed. NIH staff will not evaluate the technical and scientific merit of the proposed trial; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How would positive or negative results provide meaningful information to advance the field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the PD(s)/PI have sufficient time and expertise to implement a high-risk trial?  If the applicant is at an early stage in his/her career, are the mentoring and support adequate at the applicant’s institution?  Does the project include an experienced project manager and/or a study coordinator to lead implementation activities at all sites?

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? Is the intervention to eliminate latent HIV infection sufficiently novel to justify any risks to subjects and the resources/effort required? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? Does the application propose a justifiable approach to eliminate cells containing integrated HIV proviral DNA?  Is the approach likely to substantially reduce the reservoir, and are the plans for measuring the effect reasonable?  Does the analysis include an appropriate sample size justification and power calculation, or an acceptable non-statistically powered justification?  Does the application provide adequate justification for the selected population?

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

Environment

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

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 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 National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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

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

Section VI. Award Administration Information
1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 awardee agrees to accept close coordination, cooperation, and participation of NIAID staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.

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

  • All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators.
  • Meeting NIH policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf
  • Hiring a Study Coordinator and Project Manager who will assist the PI in closely monitoring study progress according to the milestone plan.  These personnel should work with the PI to distribute timely information to facilitate DAIDS site approval, protocol activation, and implementation of the trial at all participating sites, if applicable. They will work with the PI to develop and distribute written documentation of progress made in accomplishing the activities described in the milestone plan to all members of the protocol team on no less than a quarterly (every 3 months) basis.  See below for additional information about the contents of these reports.
  • Holding regular Protocol Steering Committee (SC) calls no less than quarterly (every 3 months) that include site PI(s), Study Coordinator(s)/Project Manager(s), the NIH Medical Officer, the NIH Program Official, and guests invited by NIH Program Staff or the PI(s) to discuss the development, approval processes, implementation, and progress towards established accrual benchmarks.
  • Providing periodic Study Update and Safety Monitoring Reports to the NIH Medical Officer and NIH Program Official no less than a quarterly (every 3 months) for the entire grant budget period. These reports should include administrative updates, progress towards important study milestones, accrual data, and aggregated adverse event data that is not sorted by treatment arm.
  • Upon implementation of the protocol, ensuring that each collaborator abides by NIH, OHRP and FDA requirements, and also adheres to the procedures required by the protocol regarding study conduct and monitoring, volunteer management, data collection, and quality control.
  • Submitting adverse event reports on an expedited basis to the NIH Medical Officer and Program Official at the same time that they are sent to the FDA and/or IRB.
  • Establishing Clinical Trials Agreements necessary to complete the proposed clinical trial.
  • Ensuring that protocol implementation and oversight adhere to the following policies and requirements:
    • establishing criteria for determining the futility of answering the research question within a pre-defined time boundary
    • obtaining protocol approval by NIH prior to protocol implementation
    • developing post-study follow-up plans, contingent upon study results, that are incorporated within the protocol and are reviewed by the DAIDS Scientific Review Committee
    • providing results to study participants upon un-blinding, if applicable, and to the community as soon as can be accomplished
    • providing timely information required by all DAIDS offices to facilitate activities such as accrual and milestone tracking in the DAIDS-Enterprise System (a database used by NIAID to support DAIDS-funded trials)
  • Participating in an annual conference call for the purpose of information and data sharing among other cure researchers
  • Establishing criteria for determining the futility of answering the research question within a pre-defined time boundary
  • Accomplishing negotiated milestones.  Awardees who do not accomplish negotiated milestones shall submit a milestone report, including a discussion of why the milestones were not met in the agreed upon timeframe, and proposing a corrective action plan. The corrective action plan shall include: amended milestones, plans to achieve the amended milestones and any additional items required by NIH staff. The plan shall be provided to NIH staff no later than 2 months following the missed milestone.
  • Submitting a close-out plan to NIH staff within 2 months of a decision either by NIH staff or the grantee that an awarded study is no longer feasible. The plan must be approved and signed by the Institutional Official and the PD(s)/PI(s) listed on the award prior to submission.
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
  • Except for licensing of patents or copyrights, notifying NIH and obtaining NIH concurrence for support or other involvement by industry or any other third party in the study.
  • Putting all study materials and procedure manuals into the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Awardees must appropriately acknowledge support by NIAID/NIMH/NIH in publications and oral presentations of work performed under this agreement.

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

  • The Project Scientist(s) (who also may be a Medical Officer) will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond the normal program stewardship role for grants, and may serve as a member of the protocol team.
  • Having access to data generated under this Cooperative Agreement and periodically reviewing the data and progress reports. NIH staff may use information obtained from the data for the preparation of internal reports on the activities of the study. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
  • Providing guidance in the development, assembly, and submission of all required regulatory documents for the FDA (e.g., those regarding the use of investigational drugs).
  • Serving as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources, advising in management and technical performance, or assisting in the preparation of publications.
  • Providing medical monitoring. A NIH Project Scientist (Medical Officer) will monitor the clinical trials and serve as the Medical Monitor. Should a pharmaceutical or biotechnology company sponsoring a clinical trial choose to name its own Medical Monitor, then the NIH Project Scientist (Medical Officer) will work with the company-assigned Medical Monitor. The NIH Project Scientist (Medical Officer) may also serve as a member of the protocol team.
  • Overseeing the adequacy of adverse event management and reporting, and having regular communications with the PD/PI and study team, which may include attendance at safety monitoring and related committee meetings.

  • Reviewing the progress of the study, and of each participating clinical research site, as needed, through consideration of the annual reports, site visits, volunteer logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.
  • Monitoring progress of study milestones. As with any award, continuation, even during the period recommended for support, is contingent upon satisfactory progress. Progress will be monitored by an internal panel with outside consultants as needed and determined by the NIH. The schedule for these interim reviews will be based upon the duration of the clinical trial period. Continuation of funding will be dependent upon the awardee’s ability to show adequate progress towards accomplishing milestones identified in the application and negotiated prior to award.
  • Closing the study for lack of progress following review and consideration by NIH staff. NIH reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to meet recruitment milestones as per criteria established pre-award, (b) failure to obtain regulatory approval within 9 months, (c) failure to implement the study protocol within 12 months, (d) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol, (e) substantive changes in the agreed-upon protocol with which NIH does not concur, (f) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (g) human subject ethical issues that may dictate a premature termination.  
  • An agency Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

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

Areas of Joint Responsibilities Include:

  • A Protocol Steering Committee (SC) will be created and will include the Program Director/Principal Investigator, as well as the principal investigators of participating sites, any data management representative or data manager, and the NIH Program Official and Medical Officer. The NIH Medical Officer will have voting membership on the SC and, as appropriate, its subcommittees. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. Awardees will be required to accept and implement all common protocol and procedures approved by the SC. As the components of the SC may be geographically dispersed, the SC should meet with at least quarterly (every 3 months, supplemented as deemed necessary by face to face meetings. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
  • Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports.  NIH staff may use information obtained from the data for the preparation of internal reports on the activities of the study 
  • Attend and interact with the study team during meetings, site visits, and conference calls

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 Protocol Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Scientific/Research Contact(s)

Tia Morton, R.N., M.S.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3073
Email: frazierti@niaid.nih.gov

Deborah Colosi, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-605-2275
Email: Deborah.Colosi@nih.gov

Peer Review Contact(s)

Peter R. Jackson
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5049  
Email: pjackson@niaid.nih.gov

Financial/Grants Management Contact(s)

Michael Fato
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2968
Email: mf59e@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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