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)

Funding Opportunity Title

Advancing HIV Therapeutic Vaccine Science (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-AI-16-019

Companion Funding Opportunity

None

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

93.855, 93.856

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits applications that will advance understanding of vaccine regimens and immune responses that sustainably suppress viral loads in HIV-infected individuals. Applications should propose small, multi-arm, comparative clinical trials designed to identify correlations between levels of induced immune response and HIV virologic control. Vaccines may be combined with adjuvants and/or other modifiers of the immune response to HIV.   

Key Dates

 

Posted Date

April 6, 2016

Open Date (Earliest Submission Date)

June 28, 2016

Letter of Intent Due Date(s)

June 28, 2016

Application Due Date(s)

July 28, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

AIDS Application Due Date(s)

July 28, 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 29, 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

This Funding Opportunity Announcement (FOA) solicits applications that will advance understanding of vaccine regimens and immune responses that sustainably suppress viral loads in HIV-infected individuals. Applications should propose small, multi-arm, comparative clinical trials designed to identify correlations between levels of induced immune response and HIV virologic control. Vaccines may be combined with adjuvants and/or other modifiers of the immune response to HIV.

Background

HIV-infected persons currently require lifelong treatment with combination antiretroviral therapy (cART). The development of therapeutic vaccines that induce HIV-controlling immune responses could end the need for lifelong treatment. However, it has proven exceptionally difficult to induce protective immune responses using vaccination strategies. Despite a number of clinical trials, effective products have not been developed.

Substantial evidence suggests immune responses can reduce viral loads (VL) in HIV-infected persons. Some individuals naturally suppress VL to very low levels without cART. These elite controllers often produce CD8 T cell responses recognizing specific HIV peptides. Other individuals maintain very low VL after cART is withdrawn. The CD4 T cells and natural killer (NK) cells in these post-treatment controllers display enhanced functional activity. Finally, some infected individuals develop broadly neutralizing HIV-specific antibodies (bNAb) that exhibit antiviral activity when cloned, manufactured and administered passively to infected animals and humans. Together, these observations suggest HIV should be susceptible to vaccination-induced, immune-mediated control. However, robust correlates of immune-mediated VL control in HIV-infected humans have yet to be identified, and there are sizable gaps in both our knowledge about the most effective mechanisms for suppressing VL and how to sustainably maintain protective responses.

Chronic inflammation and immune dysregulation persist in HIV-infected individuals despite VL suppression with cART. These conditions have a variety of effects on immunity that may interfere with vaccine responsiveness. One prominent aspect of the dysregulation is T cell exhaustion, characterized phenotypically by upregulated expression on T cells of "checkpoint" receptors like PD-1. In experimental models of HIV infection, and in human cancer patients, therapeutic blockade of checkpoint pathways can increase and/or broaden T cell responses. Thus, therapeutic vaccine strategies for HIV may benefit from co-administration of immunomodulatory or anti-inflammatory agents that antagonize suppressive checkpoint or inflammatory pathways.

The VL rebound that follows withdrawal of cART is thought to result from activation of HIV reservoirs comprised of latently infected cells containing integrated HIV DNA. The latently infected cells may be invisible to the immune system if they do not express sufficient levels of HIV antigens. It may be possible to expose these quiescent reservoirs through the use of latency reversing agents (e.g. HDAC inhibitors, PKC agonists, TLR7 agonists). However, some reservoirs may reside within "sanctuaries" that are inaccessible to cytotoxic T cells. Thus, therapeutic vaccine strategies targeting HIV reservoirs may benefit from co-administration of agents that activate latent reservoirs to induce the expression of antigens and/or disrupt the capacity of HIV to hide within sanctuary sites.

Perhaps the largest challenge to therapeutic vaccine strategies is the capacity of HIV to escape from immune responses. The dominant T cell responses elicited during acute HIV infection typically target regions of the virus that can mutate without substantially diminishing viral fitness, and the HIV reservoirs in patients on cART are replete with proviruses harboring mutations that have escaped from dominant T cell responses. Therapeutic vaccine strategies may need to overcome the robust priming of these dominant but ineffective responses. Rather, such strategies may need to target conserved regions of HIV that are unable to mutate without compromising viral fitness. Unfortunately, those responses naturally tend to be subdominant, if present at all. Thus, therapeutic vaccine strategies may need to overcome "original antigenic sin" to break natural immunodominance hierarchies in order to prime or boost responses to subdominant conserved regions and/or expand the breadth of responses, perhaps by including and excluding specific regions of the HIV genome in vaccine constructs.

In addition to evading recognition by T cells, HIV also escapes from B cell responses. Moreover, carbohydrates shield HIV virions, making it difficult for antibodies to bind and neutralize their envelope glycoproteins. Nevertheless, some individuals produce measurable titers of bNAb that recognize many HIV variants. Much effort is currently focused on learning how to coax the immune system to produce bNAb more efficiently. Researchers are designing sets of immunogens engineered to guide the de novo maturation of bNAb-producing B cells. While primarily designed for preventive HIV vaccines, some of these constructs may be useful in therapeutic settings as well. Interestingly, preventive vaccine trials have suggested non-neutralizing antibodies also can protect against HIV, perhaps via antibody-dependent cell-mediated cytotoxicity or phagocytosis. Thus, the induction or administration of HIV-specific antibodies may be an important component of HIV therapeutic vaccine strategies.

Research Objectives and Scope

The goal of this FOA is to support research that will advance understanding of vaccine regimens and immune responses that sustainably suppress viral loads in HIV-infected individuals. Specifically, it will support hypothesis-driven mechanistic studies utilizing small, comparative, multi-arm, clinical trials of virologically suppressed, HIV-infected individuals on cART. Vaccination approaches that aim to sustainably elicit, boost and/or activate HIV-specific T cells, NK cells, antibodies, or other effector mechanisms are responsive to this FOA, as are approaches that aim to elicit combinations of protective mechanisms.

This FOA will also support a follow-on trial designed to confirm the observed correlations between specific immune response and virologic control and to further optimize the response. The goal is to incrementally develop effective therapeutic vaccination strategies by methodically increasing our understanding of protective responses and then working iteratively to improve the potency of those responses. In lieu of a second trial, an adaptive trial design can be proposed.

The target population is HIV-infected individuals virologically suppressed by cART. Accordingly, the proposed readout assays should be chosen to quantify the effects of the therapeutic interventions on measures of persistent virus production and/or the active HIV reservoir in this population (e.g. single copy assays, cell-associated HIV RNA assays). The use of functional assays (e.g. viral inhibition/suppression assays) and extensive characterization of responses pre- and post-vaccination is encouraged, as is the development and use of novel immune and virologic assays.

The proposed interventions must include vaccines, perhaps in combination with adjuvants and/or other modifiers of the immune response to HIV. To ensure timely initiation of the proposed studies, applicants are strongly encouraged to use agents already approved for human use or agents that are ready to be tested in clinical trials, particularly for the first trial. The initial trial must open to enrollment within 12 months of award and can be conducted at no more than 2 clinical research sites located within the United States.  

Specific areas of interest

  • Vaccination strategies designed to harness HIV-specific T cell, B cell, or NK cell effector functions, elicit de novo HIV-specific responses, or broaden existing responses
  • Comparisons of vaccine vectors, HIV immunogen constructs, vaccine adjuvants, vaccine or adjunct dosages, or the order and timing of treatments
  • Combinations of vaccines and exhaustion/checkpoint pathway antagonists, anti-inflammatory agents, latency-reversing agents, sanctuary-disrupting agents, or HIV-specific monoclonal antibodies
  • Endpoints based on correlations between measures of immunity and virologic criteria
  • Other immunotherapeutic approaches

Applications including the following types of research will be considered non-responsive and will not be reviewed:

  • Animal models of HIV infection
  • Vaccine strategies that primarily aim to boost dominant existing responses
  • Comparisons of a single treatment arm versus a placebo arm
  • Treatment interruptions as the primary means to evaluate virologic control
  • Clinical trials that are conducted outside of the U.S.

Clinical Trial and Regulatory Support

All clinical trial planning activities for the first trial must be completed by the time of application. Investigators must implement the first trial within 12 months of receiving the award.

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).

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

  • Regulatory activities to support implementation of the trial
  • Training of study personnel related to conduct of the trial
  • Enrollment and recruitment of study subjects
  • Data collection, management, and quality control
  • 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

NIAID reserves the right to specify whether an Investigational New Drug (IND) application should be submitted to the FDA and, if so, to specify the sponsor who will hold the IND. In most cases, it is expected that the NIAID will not hold the IND.

Applicants should review the NIAID Clinical Terms of Award and associated guidance documents, policies, and procedures that will be made terms of these awards (http://www.niaid.nih.gov/researchfunding/sci/human/Pages/clinterm.aspx), and the DAIDS Clinical Research Policies and Standard Procedures Documents (http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Pages/Default.aspx) that describe requirements for DAIDS-funded clinical research.

Milestones

Delineation of milestones is a key characteristic of clinical trial awards made under this announcement.  A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.  Awards will include a Milestone Plan that includes opening enrollment within 12 months of award and completing the clinical trial within the period of award. The milestones will be incorporated into the terms of award.

A Scientific Advisory Board will be established by the applicant, approved by NIAID staff, and convened annually to review progress and provide the applicant and NIAID staff with evaluations, advice, and recommendations concerning the ongoing and planned research activities.

NIAID may reduce funds or the period of performance based on lack of achievement of yearly milestones.    

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

NIAID intends to commit $3.6M in FY 2017 to fund 2-3 awards.

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.

U.S.-based institutions must receive primary awards through this FOA. Foreign collaborators are permitted if scientifically justified and feasible given the proposed study design, but the clinical site(s) must be located in the United States.  

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.
  • 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 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 Jackson, Ph.D.
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.

Other Attachments: The following attachments are required for this FOA, and must be included as separate pdf attachments.

1. Clinical Protocol Synopsis

The filename "Clinical Protocol Synopsis.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. The synopsis is limited to 2 pages, should briefly describe the first trial to be performed, must not duplicate information provided in the Research Strategy, and must include the following sections limited to the specific protocol of the first trial:

Title

Participating sites

Hypothesis, i.e., a brief statement to justify the trial

Interventions

Study design, including schedule of interventions, procedures and evaluations

Study population, including sample size and subject inclusion/exclusion criteria

Immunologic and virologic endpoints

Rationale, including justification for the selected endpoints and intervention(s)

Applications that lack the Clinical Protocol Synopsis are incomplete and will not be peer reviewed.

2. Milestone Plan

The filename "Milestone Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. The milestone plan is limited to 2 pages and should include a timeline for the following:

Pre-IND meeting with the FDA, unless the FDA determined a meeting was not necessary or granted an IND exemption for the trial

  • Regulatory approval of the clinical protocol
  • Submission of Clinical Protocols and Subject Informed Consent Forms for NIAID review
  • Recombinant DNA Advisory Committee (RAC) review, if applicable
  • Open to accrual and enrollment within twelve months of award
  • Close to patient follow-up
  • Completion of data analysis
  • Completion of the first trial and follow-on trial within the period of the award
  • Final study report
  • Submission of publication

Applications that lack the Milestone Plan are incomplete and will not be reviewed.  The Milestone Plan will be incorporated into the terms of award.

3. Complete Clinical Protocol

The filename "Complete Clinical Protocol.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. There is no page limit for this section but applicants are urged to be succinct.

The complete Clinical Protocol must include the Subject Informed Consent Forms. The Protocol should describe the first trial to be performed. 

Investigators are referred to the Trans-NIAID Clinical Research Toolkit website for clinical protocol guidance and templates (http://www3.niaid.nih.gov/LabsAndResources/resources/toolkit/protocol).

Applications that lack the Complete Clinical Protocol are incomplete and will not be reviewed.

4. Regulatory Activities

The filename "Regulatory Activities.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. There is no page limit for this section but applicants are urged to be succinct.

Describe plans and capability to provide regulatory support for the development and implementation of the clinical trial. State whether an IND/IDE is necessary for the proposed trial. If an IND/IDE is necessary, identify the sponsor.

Describe previous and planned interactions with the FDA on the proposed clinical trial. If a pre-IND meeting request was 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 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, or
  • a copy of the FDA letter granting an IND/IDE exemption letter for the proposed trial

Describe a data management approach 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.

Applications that lack the Regulatory Activities plan are incomplete and will not be reviewed.

5. Laboratory Assays for Measuring Vaccine-Induced Responses

The filename "Laboratory Assays.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. There is no page limit for this section but applicants are urged to be succinct.

Describe the assays proposed to measure vaccine-induced immune and virologic responses. Provide data or references supporting the reliability of the assays and validity for their use. Describe plans to adhere to NIAID's policies when proposing endpoint assays that are for investigational use only, and not approved by the FDA nor validated by the International Council for Harmonisation (ICH) or U.S. Pharmacopeia. 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. Address compliance with Good Clinical Laboratory Practices (GCLP) and for performing proficiency assessments. For guidance, see: http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Pages/reqUSLab.aspx

Describe plans to maximize the number of immune/virologic endpoints measured and the quality of the assays by leveraging resources, collaborations, and/or sources of external support.

Applications that lack the Laboratory Assays plan are incomplete and will not be reviewed.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

Funding needs for the entire trial including second trials or adaptive design trials and data analysis must be addressed. All changes in budgets after the first year should be clearly identified and justified. Any sources of support for the trial outside of this award  should be noted in the budget justification and documented by a letter of support. Costs covered by outside support need not be included in the requested budget. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement.

Applicants should include appropriate travel budgets to accommodate travel by Scientific Advisory Board members to an annual meeting.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: State the hypothesis, goals and expected outcomes of the proposed intervention(s) Specific attention should be given to the rationale for the proposed vaccination strategy, including its capacity to elicit the desired immune responses and the hypothesized mechanisms of action that will lead to a measurable virologic effect.

Research Strategy: The Research Strategy is comprised of three sections (Significance, Innovation, and Approach) and without duplicating information provided in the Clinical Protocol Synopsis must include:

a hypothesis proposing a means to induce an immune response, or set of responses, that will exert a measurable virologic effect in HIV-infected humans taking effective antiretroviral therapy

a rationale for the proposed immunotherapeutic intervention, or combination of interventions, chosen to induce or augment the desired immune responses. This rationale should justify the selection of the specific intervention identified in the clinical protocol synopsis

  • a rationale for the choice of the primary immunologic and virologic endpoints
  • the overall strategy, methodology and analyses, including the clinical trial stages and criteria for completion of each stage. Explain the overall rationale for the trial design with an emphasis on how it will test the hypothesis. The strategy must include a multi-arm clinical trial designed to induce the desired immune responses to varying degrees and demonstrate correlations between the levels of the induced immune responses and measures of virologic control. The strategy must also include plans for a follow-on trial (or propose an adaptive trial design) that will advance the goal of incrementally developing an effective therapeutic vaccination strategy by increasing understanding of protective responses and working iteratively to improve the potency of those responses. A detailed description of the follow-on trial is not required. Rather, the application must describe the rationale and general design for the follow-on trial. One key goal should be to replicate any correlations observed in the first trial.
  • the reasons for the choice of the: study population; subject eligibility, inclusion and exclusion; and the plans for recruitment/enrollment and futility assessments
  • a plan and timeline for acquiring study products. If the interventions planned for the follow-on study are not yet ready for testing in humans, describe plans to ensure that those interventions will be ready in time for the trial.
  • the statistical methods, including sample size and power calculations and the underlying assumptions (and data) used to link these calculations to the endpoints and to the hypothesis being tested. Even for small, exploratory studies seeking preliminary data to guide further research, justify cohort sizes using either power calculations or non-statistically powered justifications. If not highly powered, explain how the study aims to establish correlations between immune and virologic responses. Efforts to minimize intra-subject variability (e.g. replicate measures around key time points) should be highlighted. Although this initiative requires multiple arms in each trial, it is acceptable to define success based on within arm results (e.g. a mean decrease in single copy assay by more than 25% indicates success). Controls should be described and justified. The use of placebo arms may be appropriate both to facilitate safety assessments and to determine whether reasonable thresholds were chosen to indicate response/success.
  • the criteria for determining whether the results from the first trial warrant additional trials aimed at further strengthening or focusing the relevant immune responses. Also describe and justify an alternative approach for the follow-on trial if the success criteria are not met.
  • the study organization, administration and management; roles of any advisory groups; oversight, responsibilities, and coordination of clinical and laboratory sites; and roles of any sub-contractors. Describe plans to organize and convene a Scientific Advisory Board but do not name any potential members of the Board in the application.
  • plans to implement and monitor Good Clinical Practices (GCP) and Good Laboratory Practices (GLP) as appropriate.

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 suppliers) include letters outlining details of the commitment (e.g. type, amount and source of support), signed by a business official on organization letterhead.

If the project 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 documentation of availability of data and/or resources to the applicant for the proposed clinical trial.

Refer to http://www.niaid.nih.gov/researchfunding/grant/pages/extraintracollab.aspx for considerations for NIH intramural scientist collaborations.

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.

PHS Inclusion Enrollment Report

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

PHS Assignment Request Form

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

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

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

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? Are positive or negative results likely to advance understanding about the immune responses induced by vaccination and their ability to control HIV?   

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(s) have sufficient time and expertise to implement complex, high-risk clinical trials?

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 approach sufficiently innovative to justify risks to study participants and the required resources?  

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 analysis include an appropriate sample size justification and power calculation, or an acceptable non-statistically powered justification?

Will the chosen interventions and approaches test the hypothesis? Will the studies advance understanding of the immunological mechanisms that can be induced by vaccination to sustainably suppress viral loads in HIV-infected humans? Are the endpoints appropriate? Is sufficient data provided or referenced to support the proposed assays? Will the assays measure the impact/correlation of the induced immune response(s) on virologic control? Was a follow-on trial (or adaptive design) proposed and justified? Were appropriate criteria proposed for determining whether the results from the first trial warrant additional trials aimed at further strengthening or focusing the relevant immune responses? In the event that those success criteria are not met, was an alternative strategy for the follow-on trial proposed and justified? Is the overall proposed strategy consistent with an iterative approach to improving HIV therapeutic vaccine regimen?

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?

Does the application adequately address Good Clinical Practices (GCP) and Good Laboratory Practices (GLP) compliance as appropriate? Are potential ethical issues adequately addressed? Is it likely that the first trial can begin within 12 months of the award? Are the Milestone Plan and regulatory approaches realistic and feasible?

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? Is there sufficient support, either internally or through consortium agreements, to comply with NIAID policies for regulatory activities, clinical trial oversight, laboratory and pharmacy activities, and data and safety monitoring?

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

  • All aspects of the 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.
  • Opening enrollment for the study no later than 12 months after award
  • Complying with NIAID Clinical Terms of Award (http://www.niaid.nih.gov/researchfunding/sci/human/pages/clinterm.aspx) and DAIDS Clinical Research Policies and Standard Procedures (http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Pages/Default.aspx)
  • Establishing Clinical Trials Agreements necessary to conduct the proposed trial.
  • Notifying NIAID and obtaining NIAID concurrence for support or other involvement by industry or any other third party in the study, except for licensing of patents or copyrights.
  • Ensuring that each clinical research site will follow the procedures required by the protocol regarding study conduct and monitoring, volunteer management, data collection, and quality control.
  • Providing periodic Study Progress and Safety Monitoring Reports to NIAID Medical Officer and NIAID Program Official no less than quarterly (every 3 months) for the entire grant budget period. These reports should include administrative updates, progress towards study milestones, accrual data, and aggregated adverse event data that is not sorted by treatment arm.
  • Collecting and, if requested, providing NIAID or a designee with samples that may be used for cross-trial comparisons.
  • Putting all study materials and procedure manuals into the public domain. Publishing and publicly disseminating results, data, and other products of the study, concordant with governance policies and protocols. Submitting manuscripts to the NIAID Program Officer upon acceptance for publication.
  • Participating in an annual conference call for the purpose of information and data sharing among other HIV vaccine researchers.
  • Establishing a Scientific Advisory Board (SAB) that convenes annually to review progress and provide the applicant and NIAID staff with evaluations, advice, and written recommendations concerning the PD(s)/PI(s) ongoing and planned research activities.
  • Accomplishing negotiated milestones and submitting a milestone report and corrective action plan if negotiated milestones are not met. The corrective action plan shall include: amended milestones, plans to achieve the amended milestones and any additional items required by NIAID staff. The plan shall be provided to NIAID staff no later than 2 months following the missed milestone.
  • Submitting a close-out plan to NIAID staff within 2 months of a decision either by NIAID 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.

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

NIAID Project Scientists will be responsible for:

  • Accessing data generated under this Cooperative Agreement and periodically reviewing the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.
  • Serving as a resource to provide scientific/programmatic support during the study period 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 regulatory documents and publications.
  • Providing medical monitoring. A NIAID Project Scientist 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 NIAID Project Scientist (Medical Monitor) will work with the company-assigned Medical Monitor. The NIAID Project Scientist may also serve as a member of the protocol team.
  • Ensuring adequacy of and overseeing adverse event management, and maintaining communications with the PD/PI and study team, which may include attendance at safety monitoring and related committee meetings.
  • Approving members of the SAB, attending the annual SAB meeting, and receiving the SAB meeting report.
  • 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.
  • Assessing progress of study milestones. Progress will be monitored by an internal panel with outside consultants as determined by NIAID. 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 NIAID staff. NIAID 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 quality control, or other major breach of the protocol, (e) substantive changes in the agreed-upon protocol with which NIAID 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.

Additionally, 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.

Areas of Joint Responsibility include: 

A Steering Committee (SC), composed of the Principal Investigator(s), Key Personnel, representatives from sites, representatives from laboratories, and one NIAID representative, the NIAID Project Scientist (). The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. As the components of the SC may be geographically dispersed, the SC should meet with monthly conference calls, supplemented as necessary by face to face meetings.

Each full member of the SC will have one vote. The NIAID Project Scientist will have voting membership. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

Stephen Smiley, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3071
Email: stephen.smiley@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Dhana Khurana
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2966
Email: khuranav@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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