Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

Funding Opportunity Title
Limited Interaction Targeted Epidemiology: Viral Suppression (LITE-VS) (UG3/UH3 Clinical Trial Optional)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-AI-22-024
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.855, 93.242, 93.279
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from investigators to enroll large, digitally-maintained cohorts of people with HIV-1 (PWH) in the United States who are not adequately virally suppressed. Applicants will need to employ sampling strategies that ensure meaningful enrollment of participants who report prior gaps in HIV care engagement and/or lack of sustained viral suppression (VS). The goal is to follow the research cohort over time to prospectively investigate trajectories of HIV care engagement and viral suppression, as well as the temporal antecedents and multilevel factors that drive changes in care engagement, antiretroviral adherence, and viral suppression. Researchers may test strategies for improved methods of screening, enrollment, and retention of cohort participants. Projects should seek to inform future interventions to promote sustained engagement in HIV care and sustained HIV viral suppression, and additionally have the option of testing digitally-delivered interventions toward that end.

Key Dates

Posted Date
April 13, 2022
Open Date (Earliest Submission Date)
July 03, 2022
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
Not Applicable Not Applicable August 03, 2022 December 2022 January 2023 March 2023

All applications are due by 5:00 PM local time of applicant organization. 

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.

Expiration Date
August 04, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support HIV epidemiology research that establishes large digitally-maintained cohorts (1000 participants or more) to prospectively investigate trajectories of HIV care engagement and viral suppression (VS), as well as temporal antecedents and multilevel predictors of changes in care engagement, antiretroviral adherence, and sustained viral suppression among persons with HIV (PWH) living in the United States. Approaches that sample meaningful numbers of PWH who have not benefited from sustained care engagement or viral suppression are needed to inform innovative programs to reduce morbidity and mortality from inadequately treated HIV and to reduce HIV transmission in the United States. The overall goal of this FOA is to support epidemiology research to advance knowledge of the predictors and barriers of viral suppression.

Although behavioral trials and interventions are optional, applicants may additionally test alternative methods of participant enrollment, retention, or other methods research relevant to developing their cohorts, and/or submit applications proposing to advance and test innovative, digitally-delivered interventions designed to promote HIV care engagement, adherence to HIV treatment, and sustained viral suppression.

Background

The development of highly effective antiretroviral (ARV) treatment strategies for HIV has transformed the epidemic. Successful ARV treatment, both reduces morbidity and mortality and is a vital strategy to prevent HIV acquisition because when the virus is at undetectable levels it cannot be transmitted (“Undetectable equals Untransmissible” or “U=U”). Maintaining undetectable HIV viral loads is associated with a significant reduction in the sexual transmission of HIV and significantly better long-term health outcomes. However, while effective treatments have been available in the U.S. for decades, the most recent U.S. data from the Centers for Disease Control and Prevention (CDC) from 2018 shows that only about two-thirds of PWH are virally suppressed within six months of HIV diagnosis. CDC defines HIV viral suppression as blood levels of less than 200 viral copies per mL; HIV is generally considered transmissible when blood levels exceed 1500 viral copies per mL.

Long-acting injectable ARV regimens are now available with even longer acting formulations being tested that may only require injections semi-annually or annually. The promise of these formulations to increase sustained viral suppression rests upon the uptake of these new medications. Information about the individual and structural factors associated with their use will be crucial to their successful uptake and ultimate value in addressing the HIV epidemic.

CDC has outlined some of the major demographic risk factors for PWH lacking adequate HIV treatment and sustained viral suppression in the U.S. Geographically, Southern states tend to have lower levels of PWH who are virally suppressed, and suppression levels for Black people have been found to be lower than for other ethnic and racial groups. However, VS outcomes are likely to be primarily influenced by broader, multilevel factors that include healthcare access and quality, social determinants of health, and individual psychosocial factors. Further research to understand these influences on long-term treatment success will be informative for advancing further interventions.

It is challenging to enroll and follow PWH in the U.S. who are not regularly engaged in HIV care. Inadequately treated PWH are a subset of those who initially test HIV positive, and, thus, studies will require large numbers of persons to be screened for HIV and, among those with HIV, additional testing is needed to identify those not virally suppressed. Technology approaches that facilitate minimally invasive participation and incentivize participation in research with little behavioral interference are key to understanding why individuals are vulnerable to inadequate HIV treatment. Research that can uncover predictors of VS and barriers to adequate care is needed to develop novel behavioral and biomedical prevention approaches that can effectively engage these PWH and develop impactful support for increased engagement and retention in care to achieve sustained VS.

Digital based epidemiology studies use remote methods (e.g., texting, phone apps, online surveys, postal mail, and package delivery) to collect participant data and samples, and they involve limited or no in-person visits. The LITE initiative (RFA-AI-16-031) previously demonstrated the effectiveness of digital approaches for screening, recruiting, and retaining very large (i.e., more than 5,000 participants) observational cohorts of individuals placed at-risk for HIV, with enough HIV seroconversions occurring on study to provide adequate statistical power for epidemiologic analysis and digital intervention trials. Similar social media approaches can be used to reach PWH in the U.S. and its territories who are poorly engaged in care and vulnerable to non-VS with its resulting higher morbidity and risk of transmitting HIV to others.

This initiative focuses on using technology to study HIV treatment behaviors and, optionally, to develop digital interventions to reach PWH whose virus is not suppressed to improve HIV treatment and prevention. Studies that use social media, texting, and internet-based technologies can operate in close to real-time. As a result, they can measure factors affecting retention in care and the use of ARV treatment strategies in the U.S. as the occur. Significant effort is underway to transform the U.S. HIV epidemic through the Ending the HIV Epidemic in the U.S. (EHE) program. As changes are implemented it will be important to have real-time data to focus treatment and prevention efforts on those PWH at greatest risk of non-VS, taking into account the thought processes, behaviors, social contexts, and structural factors that impede the benefits of HIV treatment. This initiative focuses on using new technologies to study HIV care continuum behaviors and, optionally, to conduct digital interventions to find better ways to reach PWH whose virus is not suppressed to improve HIV treatment and prevention.

Further scientific advances in digitally delivered interventions to promote HIV care engagement, adherence, and sustained viral suppression are needed as well. Digital clinical trials offer a number of advantages relative to clinical trials conducted through “brick-and-mortar” locations: 1) the preponderance of U.S. persons, including PWH, who demonstrate ready access to the Internet at least through their smartphones, if not computers; (2) the broad use and acceptability of home-delivery services in the U.S.; (3) the remarkably large study sizes attainable through digital enrollment methods that allow rapid screening of large numbers of potential participants and focused recruitment of those PWH most at risk of HIV non-suppression; 4) the ability of electronic cohort studies to engage PWH without geographic barriers, for example in rural, underserved areas or in subgroups, such as young men who have sex with men (YMSM) or transgender persons or persons who inject drugs (PWID) who are spread thinly throughout the U.S.; 5) the ability to rapidly enroll participants using smartphone apps and other electronic methods facilitates digital clinical trials that can be conducted more rapidly than clinic- or community-based clinical trials, and, thus, results can be more quickly available to inform resource allocation; and 6) digital interventions, because of lower costs than traditional clinic-based studies, are inherently scalable and can be implemented inexpensively if found useful.

Research Objectives and Scope

This FOA is intended to generate information needed to develop public health interventions to improve HIV treatment and reduce HIV transmission in the U.S., including Puerto Rico and other U.S. territories by increasing our understanding of non-VS and VS. Study teams must develop technology-focused approaches and demonstrate the capacity to enroll large numbers (1,000+) of PWH, focusing especially on individuals who have not benefitted from consistent HIV care engagement or sustained viral suppression. Enrollment success will be measured by the ability of the study to obtain the following:
 

  • Sufficient numbers of participants with unsuppressed HIV ( 200 viral copies/mL), and especially those with viral loads of 1500 copies/mL and above, levels at which HIV can more readily be transmitted, to conduct clinically meaningful and statistically significant research on transition between non-VS and VS states. Cohorts need to be large enough to allow for sufficiently detailed research that brings new understanding of the likelihood of obtaining and utilizing appropriate HIV care for virus control.
  • In the setting of complex interactions between individual and contextual factors, applications must demonstrate sufficient statistical power to advance knowledge of HIV treatment, identify the subgroups of PWH most at risk of non-suppression, and identify points of intervention to advance suppression.
  • Applicants will be expected to establish and meet enrollment milestones for their studies, including overall enrollment goals, benchmarks for stratified over-enrollment of youth, racial/ethnic minorities, PWID, and rural residents (i.e., PWH living outside Metropolitan Statistical Areas), as well as numbers of PWH with high viral loads or a consistent history of non-VS.
  • Cohorts must contain at least 40% of participants who self-identify as Black/African American.

A secondary goal of this FOA is to facilitate interactions among awardees to share approaches, data, and methods, and to develop harmonization standards. Investigators applying to this FOA need to plan for and attend conference calls and annual meetings focused on cohort enrollment, testing, follow-up, data analysis, and, if appropriate, intervention development.

Studies of particular interest include:

  • Identification of geographic areas and key sub-populations where improved HIV treatment efforts are most needed.
  • Characterization of rates of sustained viral suppression across PWH as well as key subgroups that may include transgender men and women, PWID or use non-injection drugs, and men who have sex with men (MSM).
  • Research to map longitudinal trajectories of HIV care engagement, antiretroviral adherence, and viral suppression among PWH.
  • Identification of predictors and temporal antecedents of changes in viral load suppression (moving from VS to non-VS; moving from non-VS to VS).
  • Studies to chart trends in and predictors of the use of long-acting injectable HIV treatment among PWH.
  • Multi-level analyses of individual and social-contextual determinants of HIV care continuum behaviors in the U.S., including care engagement and antiretroviral adherence.
  • Geospatial analyses of patterns of HIV treatment behaviors and outcomes in both rural and urban areas of the U.S.
  • Incorporation of distance-based assays and novel methods for documenting HIV care engagement, antiretroviral adherence, and/or viral suppression
  • Studies using the assembled cohorts to investigate patterns of HIV testing and mechanisms to optimize testing frequency and rapid linkage to treatment.
  • Studies addressing intersectional stigma and discrimination, mental health and substance use, and other psychosocial factors as determinants of engagement of PWH in HIV treatment.
  • Studies that consider geospatial distribution of services for HIV treatment and for treatment of comorbidities such as STIs, viral hepatitis, and psychiatric disorders (including substance use disorder), with consideration of how these services may be co-located or networked within systems of health care and public health.
  • Development and testing of scalable, digitally delivered HIV treatment interventions that promote better HIV treatment among high-risk groups through digital clinical trials.
     

Applications including the following types of studies will be considered non-responsive andwill notbe reviewed:
 

  • Studies of participants residing outside the U.S. or its territories. Foreign components are permitted where they support domestic U.S. research.
  • Studies not proposing the use of technology-focused approaches to establish and follow cohorts of PWH for epidemiologic research.
  • Studies that are not programmed to recruit and enroll study groups that include reasonable numbers of PWH at high risk of HIV non-VS where at least 40% of planned participants are self-identified as Black/African American.
  • Studies planning to enroll fewer than 1,000 individuals that cannot demonstrate adequate statistical power for a study.
  • Studies proposing a clinical trial that requires an IND.
  • Studies lacking clearly described timelines for the UG3 and UH3 phases and studies lacking clearly defined and quantifiable Go/No-Go Transition Milestones.

UG3/UH3 Phased Innovation Awards

Applications must be structured around two phases. The UG3 (Phase 1) will focus on a two-year award to demonstrate enrollment and retention of sufficient numbers of participants from populations of PWH most likely not to be retained in HIV care nor virally suppressed. The UH3 (Phase 2) will focus on an additional three years of funding to conduct epidemiologic research to advance further knowledge of when, where, and how lack of sustained viral suppression among PWH currently occurs in the U.S. and may include clinical trials to test digitally delivered interventions to promote HIV care engagement, ART adherence, and viral suppression. Transition to the UH3 award will be determined by an administrative and scientific evaluation by NIH staff of Go/No-Go Transition Milestones accomplishment, including meeting enrollment targets and the preparedness of the cohort to implement the proposed epidemiology and optional intervention studies, as well as programmatic priorities and availability of funds.

Applications must include Go/No-Go Transition Milestones to be assessed at the end of the UG3. Funding of the UG3 (Phase 1) does not guarantee support of the UH3 (Phase 2) award for research implementation, and it is anticipated that not all funded UG3 projects will transition to the UH3 phase. A programmatic evaluation by the NIH will determine the transition to the UH3 phase based on Go/No-Go Transition Milestones accomplishment, (i.e., demonstration that investigators enrolled and retained significant numbers of PWH who were either not in care or not virally suppressed at baseline). Continued programmatic priorities and availability of funds also will impact the decision to transition to the UH3 award. Appeals of the transition decision will not be accepted.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

Funds Available and Anticipated Number of Awards

The following NIH components intend to commit the following amounts in FY 2023 to fund 3-4 total awards:

NIAID, $3.0M

NIMH, $0.6M

NIDA, $1.0M

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

The scope of the proposed project should determine the project period. The project period may be up to 5 years: up to 2 years for the first phase (UG3) and up to 3 years for the second phase (UH3).

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

  • 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 Government

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • 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.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
    • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.
  • eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide 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.

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:

Poonam Pegu, Ph.D.
Telephone: 240-292-0719
Email: poonam.pegu@nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims:

Provide the overall goals or hypotheses for the entire project and indicate separate Specific Aims to be accomplished in the UG3 and UH3 phases. Clearly state the importance of the research question in terms of advancing HIV treatment among PWH in the U.S. at high likelihood of HIV non-suppression. Explain the need for and timeliness of the planned studies, including a digital intervention trial, if that is planned.

Research Strategy:

Without duplicating information in the biosketches, please describe any previous experience in performing the following activities: enrollment of PWH at high risk of non-VS, including documenting their minority status, age, rural or urban status, and sexual risk status, as well as measuring retention rates, and annual changes in viral suppression status.

Provide detailed descriptions of any supporting data and experimental approach for the following:

  • A discussion of the significance of the proposed research to define subgroups of PWH in the U.S. at highest likelihood of HIV non-suppression.
  • A description of the cohort recruitment, enrollment, and follow-up approaches. This should include information on access to appropriate populations, including a discussion of how one’s findings would impact any potential treatment intervention’s cost and scalability, and how one’s research approach will minimize barriers associated with bias and loss to follow-up.
  • Use of digital methods for recruitment and participant follow-up activities including the working definition of retention and the methods for qualitatively evaluating and improving the recruitment and retention process.
  • In the context of a digital approach, strategies to access and enroll PWH at high risk of non-suppression, including transgender persons, PWID or people who use drugs, and MSM, and for oversampling special populations such as youth, Black people, and rural residents who may have acquired HIV.
  • Strategies in digital settings to ensure that participants are enrolled only once in the funded study (i.e., no duplicate enrollments), and strategies to verify the race, sex, and age of participants, and, if appropriate, the use of injection and other drugs. Also strategies to document that all participants are living in the U.S. or its territories.
  • Unique statistical analysis challenges posed by an HIV suppression endpoint and approaches to manage other expected study outcomes.
  • Plans to determine the HIV status of the cohort at baseline. Include a description of the methods to determine the HIV status of participants in a non-clinic setting, such as screening programs, home-based tests, HIV self-tests, electronic medical records and self-report. Applicants are encouraged to explore the pros and cons of different approaches for feasibility, cost, and veracity among other parameters.
  • Prediction of expected numbers of non-suppressed PWH who become suppressed during follow-up, and, if an optional trial is planned, after receiving or not receiving optional HIV treatment interventions.
  • Strategy to assess contextual and other factors potentially associated with HIV non-suppression or its surrogate measures such as adherence to ARV medications.
  • If the application involves children under age 18 years, describe any specific adjustments needed from the plan for adults.
  • Discuss any impediments that could require an addendum to the research plan, milestone, or timeline with a discussion of alternative approaches.
  • For the UH3 (years 3-5), include a description of planned research to understand individual and contextual predictors of HIV suppression and identify actionable approaches to expand epidemiologic knowledge and optimize HIV treatment.
  • A description of the hypotheses to be tested in the UH3 phase of the study.
  • Plans to measure thought processes and behaviors, including risk and health seeking behaviors of the cohort.
  • A strategy to assess contextual factors potentially associated with HIV non-suppression.
  • A description of the analytic plan for the UH3 phase, including statistical and other methods to be employed.

Timelines

Applicants are required to propose well-defined timelines for the entire project, i.e., both the UG3 and the UH3 phases. Applications must describe timelines that could include, but are not limited to, meeting stated enrollment targets and retention rates of members of specified cohorts, with specified numbers of participants with HIV who are not retained in care or not virally suppressed at baseline, annual HIV-suppression rates and the detection of a specified number of previously un-suppressed PWH who become suppressed within the two-year period of the UG3 phase.

Go/No-Go Transition Milestones for the transition from the UG3 Phase to the UH3 Phase

Applicants are required to include clearly identified Go/No-Go transition milestones for completing the UG3 phase at the end of Year 2 and transition to the UH3 phase for three years of additional funding. The Go/No-Go transition milestones chosen by the applicant must be quantifiable and identify critical parameters that demonstrate the recruitment of an appropriate cohort that meets the proposed non-suppression requirements. A restatement of an application’s specific aims is not considered an adequate Go/No-Go transition milestone. Applicants may use Gantt charts or other graphics to support the timelines and the Go/No-Go Transition Milestones.

The following is an example of a possible Go/No-Go transition milestone. Applications must propose specific Go/No-Go transition milestones in the context of their proposed research and are not limited to this example:

The proposed study will enroll a total of (fill in the number) MSM, cis or transgender persons, PWID, or other PWH who are not currently virally suppressed, enrolling (fill in percentage) of participants who have HIV viral loads of 1500 copies/mL or higher and (fill in percentage) of participants who have minority status. The study retention rate will be (fill in percentage) or higher.

Note: Applicants are required to enroll at least 1,000 PWH or to justify enrolling fewer participants and at least 40% of participants who are enrolled must self-identify as Black/African American.

Applicants are encouraged to review specific NIH policies regarding “Research Involving Human Subjects”. Information about enrolling adolescents in clinical research is available at the following web site: https://www.niaid.nih.gov/research/daids-clinical-research-protocol-informed-consent.

Describe the following, including any differences between the UG3 and the UH3 phases:

  • Describe any data sources to be employed.
  • Provide documentation of access to data sources.
  • Provide a draft privacy policy, as applicable.

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, 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 in the Letters of Support.

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. Investigators will be expected to develop data structures that are findable, accessible, interoperable, and reliable. This will produce data sets that are harmonized and facilitate progressive data sharing models. Resources generated by awardees are expected to be shared with the broader scientific community for research. Applications are, therefore, expected to provide a well-thought-out plan for widely sharing data and resources generated by each research project. After all awards have been made, the investigators will develop a unified policy for data and resource release, and each application is expected to include a statement that the investigators will abide by the Consortium’s data and resource policy, consistent with the relevant NIH policies, laws and regulations. Use of Common Data Elements (CDEs) such as those defined on the National Library of Medicine website is encouraged.

It is anticipated that applicants may propose new approaches for informed consent that improve participant understanding and allow for use of data across a range of health and other electronic platforms.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical 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, with the following additional instructions:

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

If proposing a clinical trial or intervention, describe unique challenges and approaches to a digital non-clinic-based recruitment plan. Describe engagement and retention strategies in the context of digital strategies.

2.7 Study Timeline

All applicants proposing trials or interventions must provide a Study Timeline for the entire duration of the award, including specific milestones for the following activities:

  • Submission of the Clinical Protocol and Subject Informed Consent Form for NIAID review.
  • Completion of regulatory approvals for the Clinical Protocol as applicable.
  • Enrollment of first participant
  • Last participant off study (must be within period of UH3 award).
  • Within this section, discuss the feasibility of achieving and completing the milestones on-time, including alternate approaches and contingencies for dealing with potential problems and impediments.

2.9 Inclusion Enrollment Report(s)

Applicants should create one Inclusion Enrollment Report (IER) or more than one IER to enable reporting depending on the scientific goals for the study and whether monitoring of inclusion enrollment would benefit from being combined or separated. NIAID recognizes that traditional definitions of a geographical site may not be relevant in this setting.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

If proposing a clinical trial or intervention, it is anticipated that a Safety Monitoring Committee should provide the appropriate level of monitoring for studies proposing optional behavioral trials. Additional guidance can be found at:

https://www.niaid.nih.gov/research/daids-clinical-research-event-reporting-safety-monitoring and https://www.niaid.nih.gov/sites/default/files/StudyProgressSafetyMonitoringPolicy.pdf.

3.5 Overall Structure of the Study Team

If clinical trials are proposed, describe the management of the study team with respect to the various roles and responsibilities that are unique to implementation and conduct of digital clinical trials. In addition, include the role of non-traditional study team members (e.g., social media consultants, privacy in digital platforms, Scientific Advisory Board, etc.) in the study team functions.

Section 4 - Protocol Synopsis

4.2 Outcome Measures

If a clinical trial is proposed, in addition to standard instructions, include innovative use of digital and remote assessment of trial measures and outcomes.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

For each required attachment, applicants proposing clinical trials must include the available information and describe the plan including the timeline/milestone for developing final versions in time to implement the clinical trial within the first 12 months.

1. Laboratory Measurement Assays

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

Describe the assays proposed to measure HIV status. Provide data or references supporting the reliability of the assays and the validity for their use. Describe plans to adhere to NIAID’s policies when proposing endpoint assays that are for investigational use only, and not approved by the FDA nor validated by the International Council for Harmonization (ICH) or U.S. Pharmacopeia. If assay results will be used to determine participant eligibility for trials or treatment decisions during trials, address plans to ensure the relevant assays are Clinical Laboratory Improvement Amendments (CLIA) compliant and performed in CLIA-certified laboratories. Address compliance with Good Clinical Laboratory Practices (GCLP) and for performing proficiency assessments. For guidance, see: https://www.niaid.nih.gov/research/daids-clinical-research-policies-and-other-information.

Describe plans for managing the quality of the assays by leveraging resources, collaborations, and/or sources of external support.

2. Clinical Site Monitoring

The filename “Clinical Site Monitoring Plan.pdf” should be used and will be reflected in the final image bookmarking for easy access for reviewers. There is no page limit for this section, but applicants are urged to be succinct.

Describe plans to conduct independent clinical site monitoring as appropriate. Refer to https://www.niaid.nih.gov/research/daids-clinical-site-implementation-operations and https://www.niaid.nih.gov/sites/default/files/crs-site-visits.pdf.

3. Good Clinical Practices, Good Laboratory Practices, and Good Manufacturing Practices

The file name “GCP, GLP, GMP Plan.pdf” should be used and will be reflected in the final image bookmarking for easy access for reviewers. There is no page limit for this section, but applicants are urged to be succinct.

Describe plans to implement and monitor Good Clinical Practices (GCP) (see NOT-OD-16-148), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP), as appropriate.

4. Regulatory Plan

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

Describe plans and capability to provide appropriate regulatory support for the development and implementation of the clinical trial.

Describe plans to comply 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.

5. Data Management Plan

The filename “Data Management Plan.pdf” should be used and will be reflected in the final image with bookmarking for easy access for reviewers. There is no page limit for this section, but applicants are urged to be succinct.

Include a description of the approach to data management and validation, including data management systems, methods of data entry and cleaning, event tracking and logistics, case report forms, and methods for monitoring the quality and consistency of the intervention(s) and data collection; policies and methods for ensuring blinding of study results; data confidentiality and subject privacy; adjudication of events (as needed); and data reports. Indicate plans for storage of data in a suitable data repository.

Delayed Onset Study

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

PHS Assignment Request Form

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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in 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.

For this particular announcement, note the following:

An application may include study design, methods, and possible interventions that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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

Significance

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

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: Are the proposed digital methods for recruitment of priority populations novel?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have 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: Are plans to access the appropriate population(s) feasible? Will the proposed research strategy lead to enrollment of adequate numbers of PWH who are vulnerable to non-VS? Is access to the appropriate population(s) sufficient? Are the methods of assessing the HIV and viral load status of the participants appropriate? Is the strategy for verifying ethnicity/race, sex, and age of the participants appropriate? Is the plan to ensure that the cohort includes discrete, non-duplicated subjects living in the U.S., including its territories, appropriate? Will the proposed enrollment plan support a statistically significant study of the individual and contextual factors associated with HIV suppression?

Is the proposed Transition Milestone feasible, quantifiable, and appropriate to demonstrate the development of the cohort with unsuppressed HIV, including participants with viral loads of 1500 copies/mL or above. Will the assembled cohort developed in Phase 1 be appropriate for readiness and feasibility to achieve the Phase 2 research goals?

Are the approaches likely to result in scalable and efficient study designs? Are the research approaches sufficiently robust to address the generalizability of the study results to populations of PWH not enrolled?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

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

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, 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 (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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.

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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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

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

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

  • The planning, direction, and execution of the proposed research, including the following: definition of objectives and approaches, implementation, data management and analysis, interpretations and publication of results.
  • Participating in the planning for meetings of award recipients, to focus on cohort enrollment, study initiation and study results.
  • Referring all participants testing HIV-positive to standard-of-care HIV treatment as defined by the IRB of record for the study.
  • Making drafts of manuscripts available for review (electronically) to the NIH Project Scientists and other NIH staff when they are circulated to co-authors and when the final manuscripts are submitted for publication. This ensures the program can maintain an up-to-date summary of program accomplishments and can prepare for press-releases of findings if warranted.
  • Prior to the end of the UG3, awardees will submit the transition package, which includes the UG3 progress report, progress toward UG3 milestones including successful enrollment of the appropriate cohort and a description of readiness to implement the UH3 research.
  • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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


During the performance of the award, the NIH Project Scientists, with assistance from other NIH scientific staff will provide appropriate assistance, advice and guidance in the design of the activities; the analysis of data; management and technical performance; and preparation of publications. In addition, the Project Scientists will serve as liaison/facilitators between the awardee, the pharmaceutical and biotechnology industries, and other government agencies (e.g., FDA, USDA, and CDC) and will serve as a resource for scientific and policy information related to the goals of the awardee's research. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus and that NIH staff will be given the opportunity to offer input into this process. The manner of reaching consensus and final decision-making authority will rest with the Principal Investigator.

The NIH Project Scientists will also:

  • Monitor study results and quality assurance across all research sites to ensure the production of high-quality, unbiased results.
  • Monitor progress towards study goals and achievement of study timelines and Go/No-Go Transition Milestones.
  • Coordinate a committee of LITE-VS award recipients and NIH staff to facilitate shared goals, enhance resource sharing and foster collaborations.
  • Facilitate access to technical resources to increase harmonization and interoperability of study datasets.
  • Periodically request research data for use in preparing internal reports on LITE-VS activities.

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

Areas of Joint Responsibility include:

  • Participate in a committee of NIAID program staff and LITE-VS award recipients to facilitate shared goals, enhance resource sharing and foster collaborations.
  • Develop a data structure that results in a findable, accessible, interoperable, and reliable dataset to be made available for controlled access public use at the end of the program.
  • Coordinate and facilitate access to LITE-VS datasets for all approved internal and external research collaborators.
  • Provide input and generate research presentations and publications of LITE-VS data.

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

3. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

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

Scientific/Research Contact(s)

Gerald B. Sharp, Dr.P.H.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3217
Email: GSharp@niaid.nih.gov

Richard A. Jenkins Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1923
Email: jenkinsri@mail.nih.gov

Michael J. Stirratt, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3875
Email: stirrattm@mail.nih.gov

Peer Review Contact(s)

Poonam Pegu, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-0719
Email: poonam.pegu@nih.gov

Financial/Grants Management Contact(s)

Mark Hodor
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5712
Email: Mark.Hodor@nih.gov

Pam 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: siscor@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.

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