EXPIRED
National Institutes of Health (NIH)
Pilot Clinical Trials to Eliminate the Latent HIV Reservoir (U01)
U01 Research Project Cooperative Agreements
Reissue of RFA-AI-13-055
RFA-AI-16-012
None
93.855, 93.856, 93.242
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.
March 10, 2016
June 26 2016
June 26, 2016
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.
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.
November 2016
January 2017
March 2017
July 27, 2016
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.
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
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.
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:
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).
Novel therapeutic vaccines and other immunological approaches that harness and enhance the patient’s immune response are of interest, including, but not limited to:
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:
This FOA will NOT support clinical trial planning activities, such as:
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:
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.
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.
New
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
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
Application budgets are not limited but need to reflect the actual needs of the proposed project.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Governments
Other
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.
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.
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.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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.
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:
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
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
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:
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:
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:
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
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.
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.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
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.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
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
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.
This initiative is not subject to intergovernmental review.
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.
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.
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.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
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.
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).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is 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?
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?
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?
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?
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?
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.
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.
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.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not Applicable
Not Applicable
Not Applicable
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.
Not Applicable
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).
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).
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.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
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:
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:
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.
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.
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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
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:
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.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
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: http://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
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
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
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
Peter R. Jackson
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5049
Email: pjackson@niaid.nih.gov
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
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.
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.