Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The cure of HIV infection in people living with HIV is one of the highest priorities of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). The goal of the Martin Delaney Collaboratory (MDC) program is to accelerate progress towards developing strategies to achieve either eradication of HIV infection from the body or a sustained viral remission, as defined by sustained viral suppression following cessation of antiretroviral therapy.Funded projects under this FOA will be expected to expand the knowledge base on HIV latency and persistence in pediatric participants, design and evaluate innovative cure strategies, develop and evaluate assays and other modalities to accurately characterize HIV reservoirs and translate findings to the clinical settings. This funding opportunity will target perinatally infected children, adolescents and young adults with a primary focus on early treated children.

The MDC program was originally established by NIAID in partnership with the National Institute of Mental Health (NIMH) in fiscal year 2011. The program is now being re-issued for open competition to include this funding opportunity focused specifically on pediatric populations. All qualified investigators are encouraged to apply; prior funding under this program is not required.

Background

The global burden of pediatric HIV infection remains high despite significant gains in prevention of HIV-1 vertical transmission, with an estimated 1.8M children 0-14 years living with HIV and 120,000 new infections in 2018. Anti-retroviral therapy (ART) global coverage for pediatric populations is slowly increasing but has limitations including suboptimal formulations, drug resistance, regimen toxicity and adherence challenges especially for pediatric populations who require life-long ART. Several unique characteristics favor consideration of pediatric populations for HIV remission and cure research. Neonates in particular have high proportions of naïve cells with low expression of CCR5 in circulating CD4+ T cells that are relatively resistant to infection compared to effector memory cells. The transmitted founder virus (T/F) crosses the placenta at a potential cost of fitness. The reservoir is likely to be homogeneous because it has not been selected by cytotoxic lymphocytes (CTL) or other immunologic pressure. Children two years of age up through adolescence can mount more robust immune responses to vaccines than adults; immunologic interventions may be more likely to be successful in children and adolescents compared with adults.

Evidence is rapidly accumulating regarding beneficial effects of early treatment initiation in children with HIV. These include significant reduction in HIV-1 reservoir burden with lower total and intact proviral DNA levels, in many cases below the level of detection of current assays. This low viral reservoir is associated with limited viral diversity. When compared with children with HIV treated later in life, early-treated children also exhibit a distinct innate immune profile consisting of distinct NK cell subset negatively associated with the frequency of intact proviral sequences. They also exhibited improved functional cellular immune responses and decreased immune activation.

Multi-disciplinary and highly collaborative efforts are needed to expand our understanding of the basic biology and dynamics of persistent HIV reservoirs and to develop effective assays, methodology, and suitable animal models to expedite research progress. Given the significant challenges in understanding viral reservoirs and developing cure strategies targeting pediatric populations, there is a crucial and unmet need for collaborative efforts to develop and test age-appropriate strategies for eradication of HIV infection or sustained control of viral rebound after cessation of ART in this population.

Research Objectives and Scope

The objective of this FOA is to support a highly collaborative and synergistic research program focused on the development of research strategies suitable for pediatric populations to achieve either a sustained viral remission or complete eradication of persistent HIV reservoirs. Applications should support academic, industry, government, and community collaboration and partnerships.The application must include at least one private sector entity (defined below) to facilitate rapid translation of basic discovery research into therapeutic development and testing. The awardee will also be required to communicate and collaborate with the awards made under the companion Martin Delaney Collaboratory program. The proposed research should be innovative and must include a combination of basic, clinical, and applied research.

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

• Characterization of host factors, viral molecular processes and pathways influencing reservoir establishment, maintenance, and elimination in HIV-infected children.
• Evaluation and understanding of the role of the developing immune system in HIV persistence throughout infancy into young adulthood (0 to 24 years old).
• Characterization of the size, dynamics, distribution, and evolution of viral reservoirs in infants, children, adolescents and young adults in both peripheral blood and tissues.
• Characterization of timing of establishment, mechanisms of persistence and strategies to target CNS reservoirs in pediatric populations.
• Development, evaluation and validation of novel technologies, as well as novel application of existing technologies for latent reservoir characterization in pediatric populations. These may include novel molecular or culture-based assays or bioimaging.
• Development, evaluation and validation of surrogate biomarkers for monitoring the reservoir and evaluation of the impact of reservoir-targeted interventions, including identification of biomarkers for post-treatment control in children.
• Development and preclinical evaluation of a robust pipeline of promising cure strategies for pediatric populations.
• Animal model optimization for pediatric studies of HIV/SIV persistence.
• Community engagement, research literacy, and qualitative research relevant to community perspectives on and engagement in cure research in children with HIV and the impact on caregivers including assessment of acceptability, preferences, attitudes and perceptions related to cure research strategies in children.
• Non-invasive imaging to characterize tissue reservoirs in pediatric populations, including the CNS.
• Research involving human specimens collected from ongoing studies including observational trials, cohorts, or from specimen biobanks
• International collaborations are encouraged; this can include but is not limited to access to international pediatric participants and use of pediatric samples from international sites.
• Applications that include characterization of reservoirs in the central nervous system, including non-invasive imaging and/or cells of the myeloid lineage, and the impact of interventions on viral rebound in this compartment will be considered for co-funding by NIMH.
• Applications that include characterization of the influence of in utero exposure to addictive substances on HIV infection, reservoir establishment and maintenance in infants will be considered for co-funding by the National Institute of Drug Abuse (NIDA).

Target population for this FOA

Target populations include children, adolescents, and young adults living with HIV with perinatal infection age from birth up to 24 years of age. Children who initiated ART very early (within the 1st week of life) are of particular interest and access to this population is required.

Examples of anticipated outcomes/goals from the collaborative research:

• Identification of viral and immune targets leading to development of reservoir-targeting strategies and strategies for sustained control of viral rebound suitable for pediatric populations
• Characterization of effects of existing reservoir targeting agents in pediatric animal models leading to a pipeline of interventions ready for clinical evaluation in pediatric populations
• Pediatric-friendly assays and tools, including biomarkers, that accurately measure the effect of reservoir-targeting strategies or predict viral rebound or control and are scalable for use in clinical trials
• Greater understanding of CNS reservoirs, their characterization and targeting
• Knowledge to inform optimization of therapeutic and cure strategies for pediatric populations with a history of exposure to addictive substances
• Strengthened community involvement and partnership to guide design and conduct of future clinical trials in pediatric populations

The research proposed is expected to push the boundaries of what is currently feasible, and it is recognized that aspects of the plan necessarily will include high-risk research or development of improved methodology and technology. Development of combination treatment strategies or gene therapy approaches would be particularly suitable for this FOA.

Some aspect of clinical research as defined by NIH (https://grants.nih.gov/grants/glossary.htm#ClinicalResearch) must be integrated into the research plan (for example, collection of tissue biopsies or leukapheresis). Clinical trials are not allowed; however, applicants are encouraged to develop clinical trial protocols and seek independent funding support to carry out trials through NIAID HIV/AIDS Clinical Trial Networks, private sector partners, U01 applications, or other funding organizations. Funding from this UM1 can be used for analysis of samples collected from separately funded clinical trials. Each Collaboratory is expected to demonstrate an ability to provide the infrastructure needed for carrying out clinical research.

Non-Responsive Areas of Research

Applications focused on any of the following or not including the required areas of scientific interest will be deemed non-responsive and will not be reviewed:

• Studies of latency reversal that do not propose innovative approaches or combinations beyond those that have already been tested in people living with HIV or are currently in clinical trials for HIV
• Strategies that would be expected to require frequent repeated delivery of interventions on par with long-acting ART strategies currently in development
• Studies focused on in vitro cell models that do not extend to primary cells isolated from treated people living with HIV
• Detailed basic immunology research not directed to the identification of targets of immune control of HIV reservoir.
• Strategies targeting only actively replicating virus, in the absence of approaches to impact latent infection.
• Strategies limited to intensified or early antiretroviral therapy without additional purging and eradication or immunologic control strategies.
• Applications focused solely on one anatomical reservoir.
• Applications focused exclusively on specific cellular reservoirs without addressing persistence in resting CD4+ T cells.
• Applications without a private sector partner and a Community Partner as defined below.
• Applications that do not include basic science, clinical research (as defined by NIH), and applied (preclinical) research as part of the overall research strategy.
• Applications proposing clinical trials
• Applications not including any research aimed at characterizing CNS reservoir in pediatric participants will not considered.
• Applications that do not include access to the target pediatric population including to cohorts of children who initiated ART very early.

Partnerships

An important part of this program is the establishment of partnerships across academia and industry to address the most important challenges in understanding, controlling, and eradicating persistent HIV infection in pediatric populations.The key investigators and institutions should provide a broad range of expertise and resources needed to accomplish the overall research goals. Cross-disciplinary partnerships that maximize innovation are highly encouraged and expected. The collaborative program should be structured to maintain focus, productivity, effective communication, and efficient management of activities.

Private sector partner. The translation of basic science findings to preclinical evaluation in age- and maturation-appropriate pediatric animal models and the design of clinical trials (to be funded under separate mechanisms) are critical goals of this program. To facilitate these activities,each application must include at least one private sector partner with commitment to contribute materially and/or intellectually to the overall goals and objectives of the Collaboratory. Private sector partners may participate in multiple Collaboratories simultaneously, as long as they do not receive duplicative funding for an identical project. Applicants are highly encouraged to seek partnerships with multiple private sector entities where possible and to establish a plan for managing intellectual property that allows for private sector partnerships to be added or changed over the course of the funding period. For the purpose of this FOA, the term “private sector” comprises large and small, domestic and foreign pharmaceutical, biotechnology, and bioengineering companies and organizations or entities (private, not for profit, foundations…) engaged in drug development. Companies providing only fee-for-service type activities or access to materials or services without intellectual involvement in the proposed research may be included in the application but will not meet the criteria for being considered a private sector partner for the purpose of satisfying these requirements.

Community engagement. Recognizing the importance of engaging community at the earliest stages of HIV cure research, the pediatric Collaboratory must include at least one Community Partner to help facilitate community engagement, increase HIV cure research literacy, gauge acceptability of potential interventions, discuss ethical considerations, and set realistic expectations for an HIV cure among communities impacted by pediatric HIV cure research. Community Partners may include community advocates with focus on pediatric populations, non-government organizations, non-profit organizations, and/or community-based organizations. Importantly, these community partnerships should be distinct from and in addition to a required Community Advisory Board (CAB). The CAB serves as an independent review board with no financial conflicts of interest. The role of the CAB will be to advise the Collaboratory’s Executive Committee on issues related to community engagement, acceptability of potential interventions, clinical trial protocol design, and ethical concerns. As such, CAB members should not receive compensation, honoraria, or travel support beyond reimbursement of expenses associated with attending CAB meetings, the annual Scientific Advisory Board (SAB) meeting, and for two CAB representatives to attend the annual joint-MDC meeting as members of an overall MDC CAB. Community Partners, however, serve as an integral part of the Collaboratory to carry out community engagement activities and may receive funding from the Collaboratory to carry out community engagement activities, including travel to scientific and community meetings at which community engagement activities are planned.

Adult MDC projects. Integration with funded adult MDC programs is a key aspect of this Pediatric MDC program and is anticipated to facilitate efficient resource sharing including collaboration with private sector partners.

Intellectual Property

Considering the collaborative nature of this funding initiative, applicants are encouraged to reach consensus among all partners, prior to application submission, regarding intellectual property, data sharing, publication agreements, and other legal matters that may arise during the program in order to ensure that the Collaboratory goals will be achieved.

Collaborative Structure

Research Program: Four Research Foci will outline plans for collaborative, synergistic research activities. There should be clear evidence of collaboration and synergy both within each Research Focus and across the four Foci. The Research Foci must be divided into the following four areas:

Research Focus 1 – Basic Research will outline plans to identify, characterize, and quantify persistent viral reservoirs and mechanisms of persistence using cutting-edge technologies, determine the sources of viral rebound, and/or determine the mechanisms of post-treatment control of viremia.

Research Focus 2– Control of Rebound: Outline plans to develop and test strategies to durably control viral rebound in the absence of ART and achieve sustained viral remission.

Research Focus 3– Eradication (or Inactivation): Outline plans to develop and test strategies to reduce reservoir size either through elimination of cells harboring rebound-competent provirus or permanent inactivation of persistent HIV, with an ultimate goal of achieving a classical cure (no remaining rebound-competent virus).

Research Focus 4 – Assay and tools development will focus on the goal of developing/optimizing assays, tools and imaging modalities adapted to pediatric populations to characterize/accurately quantify replication-competent reservoirs in clinical pediatric samples or in suitable animal models.

At least one of the research foci must include research targeting CNS reservoir in pediatric population.

Management and Operations will provide the overall coordination for central Collaboratory activities such as administrative tasks, communication, data sharing, strategic planning, adherence to timelines, resource allocation, tracking of publications and other metrics, and establishing efficient processes for activities across multiple institutions.

Executive Committee and Scientific Advisory Board. Each Collaboratory will include an Executive Committee (EC) and Scientific Advisory Board (SAB). The Executive Committee is an internal committee that will serve as the governing body of the Collaboratory, assisting the PD/PI(s) in setting the direction of scientific activities based on ongoing evaluations of research priorities and opportunities. EC should put in place policies and procedures to support operations and scientific progress, including the reallocation of funds, development of needed working groups, engagement of new collaborators and/or technologies relevant to the evolving scientific priorities, and establishment of guidelines for presentation and publication of the results of collaborative projects. The EC will be comprised of 3-5 voting members, chaired by the PD/PI(s), and should include 2-4 key personnel representing leadership of the Research Foci. Inclusion of industry partners, Community Partners, and/or CAB representatives on the Executive Committee as non-voting members may be considered but is not required. The SAB will be an independent, external advisory body that acts as a resource for the Principal Investigator and the Executive Committee, but it will not be involved in the day-to-day activities of the Collaboratory. The SAB should include at least 4 active members not affiliated with the applicant institution(s) or other institutions receiving funds from the award. The SAB will assist in review of research productivity, progress toward the proposed goals, adherence to timelines, and the continued relevance of the research approach. The SAB may recommend new scientific directions or re-prioritization of research as appropriate.

Community Engagement will outline plans for forming and managing productive partnerships with community stakeholders that will be impacted by pediatric HIV cure-related research in order to facilitate communication, increase research literacy, set realistic expectations, and discuss ethical concerns. Research addressing aspects of community engagement in HIV Cure research is children is encouraged as part of this FOA and should be relevant to research foci as delineated above.

Applicants are highly encouraged to contact the Scientific/Research Contacts to discuss their proposal and arrange a pre-application meeting prior to submission of their application.

Applicants are encouraged to leverage other resources and develop creative collaborations where possible to support the overall goals of the Collaboratory. Institutional support is highly encouraged.

A companion funding opportunity (RFA-AI-20-035) encourages applications for “Martin Delaney Collaboratories for HIV Cure Research” to address major obstacles to the eradication (cure) of HIV infection or long-term ART-free control of viral rebound (remission) in infected adult individuals.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IDF number) is allowed to either this FOA or the companion FOA for the adult Martin Delaney Collaboratories for HIV Cure Research (RFA-AI-20-035) . An institution may not submit one application to this FOA and one application to the adult MDC FOA. However, a given institution may receive funds through subawards from more than one application.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Letter of Intent

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

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

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

The letter of intent should be sent to:

Bruce Sundstrom, Ph.D.

Telephone: 240-669-5045

Email: sundstromj@niaid.nih.gov

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

, with the following additional instructions:

The Research Strategy should consist of the following sub-sections with the indicated page limits:

Subsection A: Collaboratory Overview - one required - 12 pages

Subsection B: Research Program:Research Foci - four required - 12 pages each

Subsection C: Management and Operations - one required - 6 pages

Subsection D: Community Engagement Plan - one required - 6 pages

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:

Facilities & Other Resources: For each clinical research site provide information on: the unique infrastructure for the research proposed such as clinical, laboratory, animal, and bioinformatics facilities; available unique resources for laboratory testing, and institutional support for the conduct of clinical research under U.S., DHHS, and NIH regulations and policies regarding human subjects.

Other Attachments: Provide the following additional materials specified below in support of the application.

Provide the following information as a PDF file with the name “Organizational Data”:

• Table of contents of the attachment
• Diagram showing the overall organizational and leadership structure
• Flow chart(s) showing processes for management and operations, including how decisions will be made regarding milestones, strategic planning, resource allocation, community engagement activities, and policies
• List of planned meetings and teleconferences to facilitate communication among Collaboratory investigators and community partners

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

R&R Budget  

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

, with the following additional instructions:

Budgets should be included for the following:

• A Program Manager to oversee day-to-day operation, organization, communication, and coordination of collaborative activities, including webinars, teleconferences, Executive Committee (EC) and Scientific Advisory Board (SAB) meetings, and to track and record metrics of productivity, including Collaboratory membership, affiliations, and positions; publications; meeting abstracts; and community engagement activities.
• A Community Engagement Coordinator (CEC) to manage the Community Engagement activities and partnerships and to coordinate CAB meetings. The CEC may be the same as, or in addition to, the Community Partner described above.
• Expenses for communication among Collaboratory investigators and industry and community partners and for outreach to outside researchers and community members via establishment and maintenance of a Collaboratory website.
• Travel and other expenses related to hosting an annual Collaboratory meeting for SAB and CAB evaluation and Strategic Planning activities (consisting of a kick-off meeting and a meeting before the end of Years 1 through 4). Travel expenses for SAB members should be included.
• Travel expenses for investigators, the Program Manager, and CEC to participate in an annual joint-MDC meeting at a domestic site to facilitate cross-Collaboratory interactions and communication.
• One SAB member should be supported to attend the annual joint-MDC meeting to participate in an overall SAB evaluation of the MDC program in conjunction with NIH staff.
• Travel expenses for CAB members to participate in annual SAB meetings, and for two CAB representatives to participate in joint Collaboratory meetings once per year as part of an overall MDC CAB.
• Expenses for community engagement and outreach activities, including funding to a Community Partner(s) to carry out such activities.

The budget justification should include a breakdown of the apportionment of funds for each of the proposed Research Foci, Operations and Management, and Community Engagement activities for the first year.The budgets for out-years should represent best estimates for the general research plan. Resource allocations are expected to change over time from what is initially proposed.

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:

Specific Aims: Outline the overarching long-range strategic objectives for the Collaboratory.Concisely and realistically describe the scientific problem(s), the hypotheses to be tested, and the plans to address the primary research questions. Although this is a follow-on to RFA-AI-15-029, this FOA supports only new applications, and specific aims should represent new programs not supported under the previous FOA.

Research Strategy: Research Strategy must consist of the clearly marked sub-sections A-D described below.

Subsection A. Collaboratory Overview

The Overview is a narrative section that summarizes the scientific agenda and strategic plan for the Collaboratory and the vision of how interrelated and complementary research efforts through academic, government, and private sector partnerships will contribute to achieving the overall Aims in ways that cannot be easily accomplished through standard research grant mechanisms.

The Scientific Agenda must include a narrative description of knowledge gaps relevant to the control and eradication of persistent HIV infection among pediatric populations and how the overall goals for the Pediatric Collaboratory will address the gaps through a dynamic program of collaborative and synergistic research strategies.Define the overall scientific questions to be addressed and the conceptual framework for how the program will move the field forward.Describe how interaction and collaboration among the proposed academic and private sector participants will bring unique expertise, activities, resources, and processes to the program and how these will facilitate translation of basic research findings toward practical application for pediatric populations.

The Strategic Plan will provide a comprehensive overview for implementing the overall Aims through innovative, interdisciplinary approaches. The Strategic Plan will demonstrate how the Pediatric Collaboratory will function to achieve the goals, including clear strategies for effective collaboration and decision-making as new findings emerge.Identification of potential bottlenecks and anticipated strategies to overcome major challenges within the pediatrics research should be included. The rapid evolution of science in this area is expected to result in periodic changes in research priorities and significant funding reallocation over the award period. The Strategic Plan must describe the following:

• Overarching milestones and timelines for the proposed research, alternative directions, and metrics for monitoring progress and performance toward scientific and therapeutic development goals

• Identification of three to five investigators who will constitute voting members of the Executive Committee (EC) for the Pediatric Collaboratory and description of how they will work with the PD(s)/PI(s) to facilitate changes in scientific focus, reallocation of funds and resources among projects and/or investigators, responses to SAB and CAB recommendations, sharing of data and scientific resources, and overall operations of the Collaboratory. Members of the EC should be representative of the four Research Foci; inclusion of industry partners, the CEC, Community Partners, and/or CAB representatives on the Executive Committee as non-voting members is encouraged but not required.

• Specific processes and approaches for activities of the PD(s)/PI(s) and EC, which may include but are not limited to the following:

• Setting and regularly re-evaluating research priorities and milestones, with evaluation of outcomes and go/no-go decisions as appropriate;

• Developing, reviewing, and approving changes in research direction and resources;
  
• Engaging and incorporating new collaborators and/or technologies relevant to the scientific priorities as opportunities evolve over the period of the award;

• Evaluating community engagement activities and ensuring proper allocation of resources.

• Importantly, PDs/PIs should demonstrate expertise in HIV persistence in pediatric populations.
  

• Strategies for managing relationships with the private sector partner(s) and for facilitating engagement with future private sector partners over the entire funding period, including management of intellectual property, proprietary information, and confidentiality among collaborators to encourage participation by multiple industry partners.

Plans for convening a required external SAB, in consultation with and subject to the approval of the NIAID Program Official and other relevant NIH Program staff as needed.The SAB should consist of at least 4 members. The SAB will meet with the Collaboratory PD(s)/PI(s), EC, and other key personnel at least once a year to review progress and provide recommendations directly to the Collaboratory PD(s)/PI(s) and to inform and update NIAID. The annual Collaboratory SAB meeting is an opportunity for scientific exchange and strategic planning for future research goals. The NIAID Program Official and other relevant NIH Program staff will attend each SAB meeting as observers.

Importantly, candidates for the SAB and CAB should not be named in the application or solicited prior to award.

Subsection B. Research Program Section: Research Foci

Each Collaboratory should be organized around a single, complex research program that allows for flexibility in research direction as the program matures and as new findings, technologies, and opportunities arise.As such, the Research Program Section must clearly delineate four areas of Research Focus, written as integrated goals of a single research program:

Research Focus 1 – Basic Research: Describe plans to identify, characterize, and quantify persistent viral reservoirs and mechanisms of persistence using cutting-edge technologies, determine the sources of viral rebound, and/or determine the mechanisms of post-treatment control of viremia.

Research Focus 2 – Control of Rebound: Outline plans to develop and test strategies to durably control viral rebound in the absence of ART and achieve sustained viral remission.

Research Focus 3 – Eradication (or Inactivation): Outline plans to develop and test strategies to reduce reservoir size either through elimination of cells harboring rebound-competent provirus or permanent inactivation of persistent HIV, with an ultimate goal of achieving a classical cure.

Research Focus 4 – Assay and tools development: Describe plans for developing/optimizing assays, tools and imaging modalities adapted to pediatric populations to characterize/accurately quantify replication-competent reservoirs in clinical pediatric samples or in suitable animal models.

The application must describe a plan to include research targeting the CNS reservoir in pediatric populations in at least one of the research foci.

For each Research Focus, describe the significance of the research, its relevance to the overall Aims and Scientific Agenda, and its synergy with other proposed research activities. Each Research Focus should describe short-term objectives, with detailed plans for the first 1-2 years, followed by more general plans and alternate strategies for the remaining years. Measurable outcomes and go/no-go criteria should be provided where appropriate, and a clear vision for future directions should be outlined, with flexibility to redirect or replace research projects as the science evolves.Describe the research design, conceptual procedures, tools, technologies, and analyses to be used to accomplish the objectives. Plans should include specific metrics for progress.Address any intellectual property issues anticipated and how private sector partner(s) will be involved.

Some aspect of clinical research as defined by NIH (https://grants.nih.gov/grants/glossary.htm#ClinicalResearch) must be integrated into the research plan. This may include observational studies, collection of clinical samples, analyses of samples from separately funded clinical trials, and/or social science or behavioral studies related to HIV cure research. Each Collaboratory is expected to demonstrate an ability to provide infrastructure needed for carrying out clinical research to be funded within the UM1. Applicants are encouraged to pursue independent support for clinical trial protocols related to the overall goals of the Collaboratory where applicable. Support may come from NIAID HIV/AIDS Clinical Trial Networks, private sector partners, U01 applications, or other funding organizations. Planning of clinical trial protocols to be developed by the Collaboratory should be discussed with NIH staff and should include review by the SAB and CAB.

Describe plans to leverage existing government-funded programs and resources where possible to secure services or common resources to support the needs of the program, such as NIAID HIV/AIDS Clinical Trial Networks, Clinical and Translational Science Awards, Centers for AIDS Research, Specialized Centers for HIV/AIDS-Related Structural Biology, Consortia for HIV/AIDS Vaccine Development, and Consortia for Innovative AIDS Research in Nonhuman Primates, and provide documentation in the application that such services and resources or willingness to collaborate will be available to the program.

Subsection C. Management and Operations Section

Pediatric Collaboratory applications must propose a Management and Operations Section responsible for the oversight and coordination of the program, including regular meetings among key personnel and day-to-day activities. The contact Collaboratory PD/PI will lead the Management and Operations activities and have overall responsibility for coordinating the entire range of Collaboratory activities, with assistance from a required Program Manager for coordination, as well as from the EC for progress evaluation, strategic planning, and major decision-making.EC voting procedures should be described.If the EC contains an even number of members, then a procedure for settling tied votes should be included. It is expected that key personnel will devote substantial effort to the Collaboratory program, particularly those involved in the EC.

The applications must describe how the Management and Operations Section will serve as a hub for the entire Pediatrics Collaboratory for overall leadership and management, regular communication and information sharing, coordination of activities, data management, and supervision of the Program. Describe specific plans and processes for establishing, tracking, reviewing, and managing milestones, and for tracking and reporting productivity, including metrics such as publications and presentations at high-profile meetings. Define clear lines of authority involving the PD/PI, EC, Program Manager, Collaboratory key personnel, SAB (unnamed), CEC, and CAB (unnamed). Clearly explain strategies for coordination of the program, problem identification and resolution, prioritization of resources, and the establishment of a strong collaborative environment for the Collaboratory, as well as plans for fiscal accountability among multiple institutions and investigators.Describe the strategy for reallocating funds to accommodate changes in projects, including discontinuing unproductive or low-priority projects and initiation of new projects.

Describe plans for coordination of resources, facilities, research and development activities and investigators across scientific areas/foci and multiple institutions/organizations. This will likely require management of funds between institutions on a scale beyond the usual research grant. The commitment of the awardee institution to facilitate the administration of subcontracts within the Collaboratory will be crucial to achieving success.

Describe plans for how the EC will regularly review Collaboratory productivity and milestones and act to ensure that the goals of the collaboratory are achieved, including reallocating funds, modifying research priorities, discontinuing unproductive or unnecessary studies, and instituting changes in resources and personnel.

Meetings. The Management and Operations section should include plans to coordinate and support the following meetings:

1. A face-to-face kick-off meeting within three months of the award (a tentative save-the-date should be established prior to award).

2. An annual Collaboratory SAB meeting (held before the end of Years 1-4) of all key personnel and partners for progress evaluation by the SAB and CAB and strategic planning in conjunction with NIH Program staff.

3. Regular Collaboratory webinars, teleconferences or videoconferences to facilitate internal sharing of information and resources, review progress, discuss current and future research directions, and ensure effective interdisciplinary interactions and collaborations. These communications should include NIH Program staff and be open to Community Partners and CAB members (if interested).

4. Monthly teleconferences between the PD(s)/PI(s) and NIAID Program Staff to discuss research progress, award administration, EC activities, SAB and CAB concerns, and changes in resource allocations or scientific direction before they are implemented.

5. Regular teleconferences and meetings of the EC to discuss research progress, strategic planning, Collaboratory policies and their implementation, and potential changes in scientific direction or resources.

6. Participation of Collaboratory key personnel, Program Manager, CEC, and two CAB representatives in an annual joint-MDC (adult and pediatric) meeting to be held at a domestic location either as a stand-alone meeting or as a satellite meeting in conjunction with another scientific conference. These meetings will serve to encourage information sharing and collaboration among the funded adult and pediatric Collaboratories and other members of the scientific research community and to avoid duplication of efforts. This will also serve as the face-to-face meeting of the overall MDC CAB, which will consist of two representatives from each funded Collaboratory. One SAB member will also be selected by the EC to attend the joint-MDC meting to participate in a review of the overall MDC program in conjunction with NIH staff.

Subsection D. Community Engagement Section

Pediatric Collaboratory applications must propose a comprehensive plan for community engagement to promote interactions with a diverse group of community stakeholders, increase HIV cure research literacy, and set realistic expectations for HIV cure research outcomes.Describe the roles of the Community Partner(s) and the CEC in community engagement activities, how the activities will be resourced, and how they will communicate with the PD(s)/PI(s) and EC.

Define the role of the CAB in reviewing research progress and community engagement activities and describe the specific process for how CAB feedback on ethical and practical concerns will be communicated back to the Collaboratory and NIH staff. It is expected that the CAB will also review separately funded clinical trial protocols related to the overall goals of the Collaboratory. In cases where a clinical trial protocol drafted within the Collaboratory is submitted to a Clinical Trial Network, it is expected that at least one CAB member will follow that protocol as it undergoes review and possible implementation by the Network, in conjunction with the Network CAB.

Describe how the CAB will be formed and assisted by the CEC, including regular meetings or teleconferences, involvement in Collaboratory meetings and teleconferences, and involvement in community engagement activities as appropriate. CAB members should not be solicited prior to award and should not be named 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.

The following modifications also apply:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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.

Significance  

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

Specific to this FOA:

Is the overall Scientific Agenda compelling, with clear rationale for the proposed approaches and Research Foci? Are the plans under each of the Research Foci scientifically meritorious? Given the very high-risk associated with the goal of developing a “classical” cure for HIV (no remaining rebound-competent virus), is the proposed research strategy for Research Focus 3 likely to move the field forward?

Investigator(s)  

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

Specific to this FOA:

Do(es) the PD(s)/PI(s) have documented leadership and management experience with large, complex, multidisciplinary research collaborations? Will the PD(s)/PI(s) and other key investigators involved devote adequate time and effort to the Collaboratory? Are the members of the Executive Committee likely to be able to effectively manage changes in research priorities and resource allocation? Do the PD(s)/PI(s) and other key investigators have demonstrated expertise in HIV persistence in pediatric populations? Will the private sector partner(s) provide expertise and/or resources not generally available in academia? Does the private sector entity have a record of past successes moving concepts to practical applications? Does the proposed private sector partnership(s) contribute materially and intellectually to the overall goals and objectives of the Collaboratory? How likely is it that the partnerships and collaborations involved will lead to critical new knowledge about HIV persistence and what is needed for sustained remission or cure?

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?

Approach  

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

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

Specific to this FOA:

Is the Strategic Plan feasible and compelling as a way to implement the Scientific Agenda? Are the approaches proposed in the Scientific Agenda coherent and focused on important aspects of HIV cure research? How well do the overall Collaboratory goals, expressed in the Scientific Agenda and Strategic Plan, address important roadblocks to the discovery and development of tools for accurate quantification of replication-competent reservoirs and a safe and effective strategy for control or eradication of HIV reservoirs in pediatric populations?

Is there synergy among the Individual Research Foci toward the central objectives of the Collaboratory? Is the value of supporting the proposed Research Foci, together, significantly greater than what could be achieved through support of each separately?

Are there appropriate plans and mechanisms for budgetary reallocation and shifting research priorities? Are there appropriate and feasible decision-making processes for incorporating new research activities in response to emerging opportunities and eliminating unproductive research projects to maintain innovation as the research evolves? Are the proposed milestones, and metrics to monitor, quantify and evaluate progress and productivity appropriate and feasible?

Is the Community Engagement Plan sufficient to facilitate communication between Collaboratory investigators and community stakeholders relevant to pediatric populations living with HIV? How well is private sector/industry partnership integrated into the planned studies?

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?

Specific to this FOA:

Do the investigators have access to participants or samples from pediatric populations living with HIV including children who initiated ART within the first few days of life?

Has the applicant described plans to leverage existing Government funded resources and provided documentation that these resources will be available to the Collaboratory investigators? Is there adequate support to manage complex funding of sub-projects across multiple institutions? Is additional institutional support provided and are other funding sources leveraged to create added value and further synergy within the Collaboratory structure?

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 thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan  

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

Vertebrate Animals  

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

Biohazards  

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

Resubmissions  

Not Applicable

Renewals  

Not Applicable

Revisions  

Not Applicable

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

Applications from Foreign Organizations  

Not Applicable

Select Agent Research  

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

Resource Sharing Plans  

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

Authentication of Key Biological and/or Chemical Resources:  

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

Budget and Period of Support  

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications will receive a written critique.

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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

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

Section VI. Award Administration Information

1. Award Notices

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. 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 https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• 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.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Planning, directing, and executing the proposed research in accordance with the proposed timeline;
• Establishing the membership and responsibilities of the Executive Committee (EC), described below, within three months of the award;
• Communication with the NIH Project Scientist regarding the status of ongoing research, changes in personnel, changes in research plans, etc.;
• Timely acquisition of any proprietary rights, including intellectual property rights, and all materials appropriate for performing the project(s);
• As part of the annual progress report, provide a summary outlining interaction among the group members and with the NIH Project Scientist(s); and a complete, cumulative list of all publications attributable to the award;
• Timely presentation/publication of work supported in part or whole by this Cooperative Agreement; prior notification of the NIH Project Scientist regarding any presentations or publications and appropriate acknowledgement of NIH support;
• Establishment and maintenance of a Collaboratory website;
• Establishment of the Scientific Advisory Board (SAB), described above, and a Community Advisory Board (CAB) within six months of the award and in consultation with the NIAID Project Scientist;
• Holding an annual SAB meeting to review progress, plan and design research activities, and establish priorities, to include the membership of the EC, key personnel, the Program Manager, CEC, SAB, CAB, and NIH Program representatives;and
• Integrating and implementing the recommendations of the SAB and CAB into the activities of the Collaboratory.

NIH Responsibilities:

• An NIAID Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
• Participation in the review and approval of changes in research activities and resource allocation;
• Facilitating access to resources and information that otherwise might not be available to the awardee;
• Advising on the management and technical performance of the projects, and coordinating with other appropriate NIH staff to provide advice or assistance to the awardee on specific scientific, technical, community engagement, or management issues;
• Facilitating interactions between the awardee and other groups of importance to the awardee, for example, NIAID Clinical Trial Networks, pharmaceutical and/or biotechnology companies, or community stakeholders;
• Providing guidance and oversight on compliance with Federal regulations related to human subjects research and IC policy on clinical research;
• Participation in the kick-off meeting, annual SAB meeting, webinars, teleconferences, and other meetings as appropriate, to review research progress and direction and to provide guidance.
• The NIH Project Scientist will participate in the activities of the Executive Committee, as a non-voting member.
• The role of NIAID will be to facilitate and not direct the activities. It is anticipated that decisions on all activities will be reached by consensus or EC majority vote and that appropriate NIAID Program staff as non-voting members will be given the opportunity to offer input. The NIAID Project Scientist will not participate as a co-author on any publications resulting from the research.
• Additionally, an agency Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned NIAID Program Official may also serve as the NIAID Project Scientist.

Areas of Joint Responsibility include:

Scientific Advisory Board: Members of the SAB are expected to attend the annual Collaboratory SAB meeting before the end of Years 1 through 4. For each SAB meeting, a chairperson of the SAB will be selected to provide the PD(s)/PI(s) and the NIAID Project Scientist with a comprehensive written evaluation of Collaboratory activities, including the Board’s recommendations, within 30 days of the annual meeting.

Executive Committee: Each voting member of the EC will have one vote. If the EC consists of an even number of voting members, then a process for resolving tied votes must be in place. Members of the Collaboratory will be required to accept and implement policies approved by the EC. The NIAID Project Scientist will act in an advisory capacity and be a non-voting member of the EC. The Program Manager may also assist with Committee administration as a non-voting member. The Executive Committee may recommend redirection of certain scientific activities due to changes in priorities or lack of productivity. Any changes in scope of the proposed scientific agenda must be approved by the NIAID Program Official and the designated Grants Management Official.

Annual Joint-MDC Meeting: In addition to the annual Collaboratory SAB meeting, a joint-MDC meeting of all Collaboratories funded under the Martin Delaney Collaboratory Program will be held annually. Attendees will include at minimum the PD(s)/PI(s) and key investigators, Program Manager, CEC, two CAB representatives and NIH staff. In addition, one SAB member from each Collaboratory will attend to review the overall MDC program.

Dispute Resolution Process

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 Executive 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. 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 regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

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

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

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

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

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

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

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

Tania B. Lombo, Ph.D.
National Institute of Allery and Infectious Diseases (NIAID)
Telephone: 301-761-7612
Email: tania.lombo@nih.gov

Eric Lorenzo, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-443-4993
Email: eric.lorenzo@nih.gov

Vasundhara Varthakavi, D.V.M., Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-2146
Email: vasundhara.varthakavi@nih.gov

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

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

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@niaid.nih.gov

Bryan Clark, M.B.A.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Pamela G. Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301- 480-1159
Email: pfleming@nida.nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: rita.sisco@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.

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.