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)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

Funding Opportunity Title
Limited Interaction Targeted Epidemiology (LITE-2): To Advance HIV Prevention (UG3/UH3 Clinical Trial Optional)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
Reissue of RFA-AI-16-031
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-AI-21-018
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.855, 93.242, 93.865, 93.279
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications that use innovative technology to conduct epidemiologic studies of large cohorts of U.S. populations at high risk of HIV acquisition: men who have sex with men (MSM), people who inject drugs (PWID), and transgender women and men, focusing especially on the minority and age groups at highest risk of HIV transmissions. The major goal is to support investigators who will use innovative electronic methods to recruit and retain large samples of persons at high risk of HIV acquisition, comparing those who become HIV-positive to those who do not, and optionally to develop and test digitally-delivered interventions that promote HIV risk reduction to reduce HIV-incidence.

Key Dates

Posted Date
April 7, 2021
Open Date (Earliest Submission Date)
July 06, 2021
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 04, 2021 December 2021 January 2022 March 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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 05, 2021
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 the large cohorts needed to identify individual and contextual predictors and correlates of HIV seroconversion among key populations experiencing new HIV diagnoses in the U.S. Approaches are needed to identify those at continued risk to inform interventions to reduce HIV transmission in the U.S. Applicants are expected to submit applications to develop innovative, technology-mediated, epidemiologic studies of U.S. populations with high rates of HIV: men who have sex with men (MSM), people who inject drugs (PWID), and transgender women and men, especially focusing on minorities and those age 13-49, and persons living in both urban and rural areas, because these are the groups in the U.S. at greatest risk of HIV. An application may focus on one of these groups or may propose to enroll across the categories. Applicants may submit applications proposing to advance and test innovative, digitally-delivered interventions designed to promote HIV risk reduction interventions that may include supporting use of pre-exposure prophylaxis (PrEP).

The major goal is to support investigators who will use innovative electronic methods to recruit, retain, and study large samples of persons vulnerable to HIV in the U.S., including its territories, comparing those who seroconvert to those who do not, and optionally to conduct interventions that promote HIV risk reduction and/or PrEP use.

Background

There is a critical need to strengthen HIV prevention in the U.S. While the HIV transmission rate domestically has declined modestly over the last decade, progress has been uneven, and rates have even risen among some subgroups. The advent of universal HIV treatment and roll-out of PrEP play a critical role in reducing transmission of HIV. However, challenges in use and adherence to PrEP remain. The ability to study areas of high rates of transmission will require renewed focus and more precise prevention approaches. According to the most recent data available from CDC, a total of 30,521 new HIV diagnoses among males were reported in 2018; 82% among MSM, 5% among PWID and 4% among MSM/PWID, with 9% attributed to heterosexual contact. Comparing CDC HIV-incidence data from 2010 to 2018, the annual number of HIV diagnoses increased among Hispanics/Latinos (18% increase), remained stable among Black/African Americans, but decreased among whites (−18%). Black males accounted for 39% of HIV diagnoses occurring among males in 2018, which is consistent with the high numbers of HIV transmissions recorded for this racial group from 2010 to 2018.

With regard to age, overall incidence rates increased from 2010 to 2018 for those age 25-34 and declined for those 13-24. In 2018, 25-34-year-olds accounted for the largest percentage of HIV transmissions among males regardless of racial/ethnic group: The second highest incidence rates occurred among age 13-24 Blacks (27% of 2018 transmissions) and Hispanics/Latinos (22%) and age 35-44 white males (21%). Ages of PWID contracting HIV were higher, with CDC reporting that about 59% of HIV transmissions occurred among people age 25-44, and 30% occurred among those age 45 and older.

Geographically, in 2018, total numbers of HIV diagnoses were highest in California, Florida, Georgia, Illinois, Louisiana, New York, and Texas; these states accounted for about half of total infections, but data are not available or are incomplete for many states. In summary, minority MSM age 13-44 and PWID age 25-49 are likely to benefit most from HIV prevention efforts in the U.S. Data is sparse, but high HIV incidence rates have also been reported for transgender populations in the U.S. About 18% of HIV diagnosed in the U.S. in 2018 occurred in rural areas or metropolitan statistical areas (MSA) with less than 500,000 residents. The Ending the HIV Epidemic: A Plan for America (EHE) initiative focuses on the 50 urban jurisdictions (48 counties and San Juan, P.R. and Washington, D.C) and 7 states with a high proportion of HIV diagnoses in rural areas that together account for about 59% of annual HIV incidence in the U.S. Additional efforts are needed to reach the other 41% of people annually acquiring HIV who are living in the approximately 2,500 counties, parishes and other local jurisdictions in the U.S. that are not currently prioritized by EHE.

Following individuals behaviorally vulnerable to HIV in the U.S. to study risk factors for HIV is challenging. Subgroups of persons vulnerable to HIV are often embedded within larger, demographically similar populations. In order to separate the relative contributions of individual and external factors in the setting of complex interactions, studies will require numbers of event outcomes only achievable within large cohorts. Technology approaches that facilitate participation that are minimally invasive and incentivized with nominal behavioral interference are likely the most promising ways to include higher-incidence populations.

Widespread access to HIV treatment and increasing rates of viral suppression bring concomitant benefits for HIV prevention, especially as more Americans become aware that, among people living with HIV (PLWH), Undetectable Equals Untransmittable (U=U). Expanded use of PrEP is also poised to contribute to a population-level reduction in HIV incidence. The preventive impact of these prevention approaches is nevertheless impeded by substantial structural challenges that limit their use. This is reflected in the racial and ethnic disparities found in PrEP uptake and late presentation to clinical care of minority individuals with untreated HIV. Effective engagement of hardly-reached populations and impactful support for HIV risk reduction strategies will require novel approaches.

Smart phones, the internet, and other wireless technologies have dramatically changed the ways that people meet and interact. They also offer new approaches to track and gather information from diverse populations, as well as ways to deliver and test HIV prevention interventions. The LITE initiative (RFA-AI-16-031) demonstrated the effectiveness of digital approaches for screening, recruiting, and retaining very large (i.e. more than 5,000 participants) observational cohorts of people vulnerable to HIV, with enough HIV seroconversions occurring on study to provide adequate statistical power for epidemiologic analysis and digital intervention trials. To assess HIV-status, LITE investigators have used postal mail and in-home HIV tests, in-home sample collection for central laboratory testing, as well as obtaining results of HIV tests conducted locally.

The studies that used these technologies operate in close to real time and measure factors affecting the use of prevention strategies, including PrEP, that affect HIV transmission in the U.S. Additional information is needed to inform HIV prevention programs, including better tailoring of prevention messages to those at greatest likelihood of HIV acquisition. These methods would also account for the thought processes, behaviors, and social contexts that increase risk of HIV transmission. This initiative focuses on using electronic communication technologies to study HIV risk behaviors and HIV seroconversions and, optionally, to conduct digital interventions to reduce HIV incidence.

Growing evidence indicates that digital interventions, delivered online or through smartphones, can advance primary HIV prevention outcomes such as reduced sexual risk behavior, decreased sexually transmitted infections (STI), and improved use of oral PrEP. Digital clinical trials use remote methods (e.g., online surveys and postal delivery) to collect participant data and samples, and they involve limited or no in-person visits. Digital clinical trials offer at least five advantages relative to clinical trials conducted through “brick-and-mortar” locations or clinical trials units (CTUs): 1) the preponderance of U.S. persons, including those at risk for HIV, have ready access to both the internet and postal services; (2) the remarkably large study sizes attainable through digital enrollment allow clinical trials to be powered on an HIV incidence outcome, as well as on outcomes related to HIV incidence, such as PrEP use, self-reported behavior change, and STI incidence; 3) electronic cohorts facilitate engagement of participants in rural, underserved areas and can overcome geographic limitations to assemble large subgroups of MSM, such as adolescents, or groups such as transgender persons or PWID who are dispersed sparsely throughout the U.S.; 4) 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 5) digital interventions are inherently scalable and can be implemented inexpensively if found useful.

Research Objectives and Scope

The primary goal of this FOA is to generate information needed to develop public health interventions to reduce HIV transmission in the U.S. Study teams must develop technology-focused approaches and demonstrate the capacity to enroll large numbers (5,000+) of HIV-negative people in high-incidence groups including: MSM, PWID, and transgender persons who have sex with men. Ages of participants should range between 13-49, depending on the risk group being included. Enrollment success will be measured by the ability of the study to obtain enough people who acquire HIV, so that meaningful and statistically significant prevention research with an HIV incidence outcome can be pursued. Cohorts will also need to be large enough to allow for sufficiently detailed research that brings new understanding of the likelihood of transmission. In the setting of complex interactions between individual and contextual factors, applications must demonstrate sufficient statistical power to advance knowledge of HIV transmission and to identify points of intervention to advance HIV prevention. Applicants will be expected to establish and meet enrollment milestones for their studies, including overall enrollment goals, any benchmarks for stratified over-enrollment of youth, racial/ethnic minorities, PWID, and rural residents, and numbers of acute HIV diagnoses at baseline or during follow-up as an indication of expected HIV incidence. MSM cohorts are required to recruit at least 50% of participants who self-identify as Black, Latino or of mixed ethnicity or race.

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 RFA 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 micro-epidemics in high HIV transmission areas (hot spots) and of key sub-populations where HIV prevention efforts are most needed. Studies in the priority areas of the EHE initiative include 48 U.S. counties, Washington DC, and San Juan, where >50% of HIV diagnoses occurred in 2017, as well as seven states with a substantial number of HIV diagnoses in rural areas.
  • Studies are also prioritized in the approximately 2,500 county and other local jurisdictions outside EHE priority areas, many of which are sparsely populated, that account for the other 41% of new HIV diagnoses. Electronic digital HIV prevention research is crucial here to reduce HIV incidence.
  • Characterization of subgroups of PWID, transgender persons, and MSM who could be prioritized for HIV prevention strategies.
  • Descriptions of risk behaviors and risk determinants in these key populations that can inform onward interventions to reduce HIV incidence.
  • Geospatial analyses of patterns of HIV in both rural and urban areas of the U.S.
  • Studies using the assembled cohorts to investigate patterns of HIV testing and mechanisms to optimize testing frequency and rapid linkage to treatment.
  • Monitoring HIV PrEP or U=U awareness, uptake, and adherence and identifying associated determinants.
  • Mental health as a determinant of HIV exposure risk and engagement in prevention strategies.
  • Multi-level analyses of individual and social-contextual determinants of HIV risk behavior or seroconversion in the U.S.
  • Efforts prioritizing youth populations, including adolescents age 13-18 years.
  • Development and testing of scalable, digitally delivered primary HIV prevention interventions that promote HIV risk reduction and may include support for PrEP use or viral suppression of HIV-positive sex partners among high risk groups through digital clinical trials.

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

  • Studies of individuals living with HIV.
  • Studies of subjects residing outside the U.S. or its territories.
  • Studies not proposing the use of technology-focused approaches to establish and follow cohorts of HIV-negatives for epidemiologic research.
  • Studies not focused on at least one of the high-incidence groups prioritized by this FOA: MSM, transgender persons, or PWID, where at least half of planned MSM participants are self-identified as Black, Hispanic, or of mixed race.
  • Studies planning to enroll fewer than 5,000 individuals that cannot demonstrate adequate statistical power for a study with an HIV-incidence outcome
  • 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 of sufficient numbers of participants from high-incidence populations. The UH3 (Phase 2) will focus on an additional three years to conduct research to advance our knowledge of when, where, why, and how HIV transmissions currently occur in the U.S. Transition to the UH3 award will be determined by a scientific evaluation by NIH staff of Go/No-Go Transition Milestone accomplishment, preparedness of the cohort to implement the proposed epidemiology and optional intervention studies, as well as programmatic priorities, and available 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. Transition to the UH3 phase will be determined by a programmatic evaluation at NIH that is based on Go/No-Go Transition Milestone accomplishment, i.e., demonstration that investigators enrolled significant numbers either of participants who recently acquired HIV before enrollment or originally HIV-negative participants who acquire HIV while under study. 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. Awardees will be required to refer all HIV-positive participants to appropriate treatment centers.

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
Renewal

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).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The following NIH components intend to commit the following amounts in FY 2022 to fund 5-6 total awards:

NIAID, $3.5M

NIMH $0.3M

NICHD $2.0M

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 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
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 not allowed. 

Required Registrations

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number 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.

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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:

Kristina S. Wickham, Ph.D.
Telephone: 301-761-5390
Email: kristina.wickham@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 phase and in the UH3 phase. Clearly state the importance of the research question in terms of advancing HIV prevention among HIV-negative U.S. persons at high likelihood of HIV seroconversion. 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 high risk populations, including documenting their minority status, age, rural or urban status, and sexual risk status, as well as measuring retention rates, and annual HIV seroconversion rates.

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

  • A discussion of the significance of the proposed research to define HIV-negative subgroups in the U.S. at highest likelihood of HIV seroconversion.
  • A description of the cohort recruitment, enrollment and follow-up approaches and access to appropriate populations, including a discussion of how one’s findings would impact any potential prevention 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 high-incidence groups, including transgender persons, PWID, and MSM, and for oversampling particular populations such as youth, racial/ethnic minorities, and rural residents who are vulnerable to HIV.
  • In the context of a digital approach, strategies to access, recruit and enroll participants under age 18 years and any special considerations for enrolling and following this population.
  • Strategies in digital settings to verify the race, sex, and age of participants and to verify injection use of drugs, including strategies to ensure that participants are enrolled only once in the funded study (i.e., no duplicate enrollments) and to document that all participants are living in the U.S. or its territories.
  • Unique statistical analysis challenges posed by an HIV incidence endpoint and approaches to manage other expected study outcomes, including a description and statistical evaluation of the sample size needed to test the study hypothesis and study the individual and contextual factors associated with HIV seroconversion.
  • Plans to determine the HIV status of the cohort, both at enrollment and during follow-up. Include a description of the methods to determine the HIV status of participants in a non-clinic setting, for example use of 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 with respect to feasibility, cost, and veracity among other parameters.
  • Prediction of expected numbers of HIV seroconversions among study participants during follow-up, and, if an optional trial is planned, after receiving or not receiving optional HIV prevention interventions. Funded studies are required to provide standard of care HIV prevention modalities, as defined by their IRB, to all participants.
  • Approaches for referring people living with HIV for treatment.
  • In the context of digital enrollment and intervention, discuss the unique needs for assessment of HIV risks for participants, including measuring HIV risks, health seeking behaviors, and PrEP uptake and use.
  • Strategy to assess contextual and other factors potentially associated with HIV seroconversion or its surrogate measures. If the application involves children, describe any specific adjustments needed from the plan for adults.
  • Plans to protect the security of participants’ personally identifiable information. A discussion of 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 research to understand individual and contextual predictors of HIV seroconversion and identify actionable approaches to expand epidemiologic knowledge and optimize HIV prevention.
  • 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 seroconversion.
  • A description of the analytic plan for the UH3 phase of the research, 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 specified enrollment targets and retention rates of members of specified cohorts, with specified numbers of participants acutely acquiring HIV at baseline, annual HIV-seroconversion rates and the detection of a specified number of HIV seroconverters within the two-year period of the UG3 phase.

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

Include clearly identified Go/No-Go transition milestones for completion of the UG3 phase at the end of Year 2 and transition to the UH3 phase for 3 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 seroconversion rate. A restatement of an application specific aim 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 Milestone.

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 number) MSM, transgender persons and/or PWID. The study retention rate will be (fill in percentage) or higher, and the annual HIV-seroconversion rate of the assembled cohort will be (fill in percentage) or higher. Thus, we expect to detect a minimum of (fill in number) of persons either having acutely acquired HIV at baseline or persons who are initially HIV-negative but who seroconvert by the end of Year 2.

Note: Applicants are required to enroll at least 5,000 people without HIV or to justify enrolling fewer participants and at least 50% of MSM participants who are enrolled must self-identify as Black, Hispanic, or of mixed race. Applications lacking clearly described timelines for the UG3 and the UH3 phases, as well as the Go/No-Go Transition Milestones will be considered non-responsive and will not be reviewed.

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, 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

For this FOA, 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/studyprogsafetymonitor.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 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-standard-procedures.

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

The UG3/UH3 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. A UG3/UH3 grant application is not required to have extensive preliminary data, background material or preliminary information, but these may be included if available. Appropriate justification for the proposed work can also be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes the UG3 and UH3 phases.

In addition, for applications involving clinical trials:

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: Do the proposed methods and approaches provide a novel approach to recruitment of the priority populations?

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 high-incidence groups prioritized by this FOA: transgender persons, MSM (at least half minority) and PWID? Is the access to the appropriate population(s) sufficient? Are the methods of assessing the HIV exposure 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. appropriate? Will the proposed enrollment plan support a statistically significant study of the individual and contextual factors associated with HIV seroconversion?

Is the proposed Transition Milestone feasible, quantifiable, and appropriate to demonstrate development of the cohort with an appropriate seroconversion rate, readiness and feasibility to achieve the Phase 2 research goals with the cohort developed in Phase 1?

Are the approaches likely to result in scalable and efficient study designs? Are the research approaches sufficiently robust to address generalizability of the study results to populations 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 this FOA: Are the Go/No-Go Transition Milestones feasible and justified?

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

For Renewals, the committee will consider the progress made in the last funding period.

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.

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.

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 awardee 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. 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.

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.

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:

  • Ensuring that all participants receive standard-of-care HIV prevention modalities as defined by the relevant IRB.
  • 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 treatment. Information about referral efforts and the treatment status of all participants who seroconvert on study is also required in annual progress reports.
  • Making drafts of manuscripts available for review (electronically) to the NIH Project Scientists and other NIH staff at the time 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 milestone including successful enrollment of the appropriate cohort (PWID, transgender persons or MSM), and detecting a sufficient number of HIV seroconversion events 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 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. 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 Milestone;
  • Coordinate a committee of LITE-2 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-2 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-2 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-2 datasets for all approved internal and external research collaborators;
  • Provide input and generate research presentations and publications of LITE-2 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, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final 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 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

Sonia Lee, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-4783
Email: leesonia@mail.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)

Kristina S. Wickham, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5390
Email: kristina.wickham@nih.gov

Financial/Grants Management Contact(s)

Jenna Briggs
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5137
Email: jenna.briggs@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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


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