Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this Funding Opportunity Announcement (FOA) is to support 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 infections in the United States. Approaches are needed to identify those at continued risk to inform interventions to further reduce HIV transmission in the United States. Applicants are expected to submit applications proposing to develop innovative, technology-mediated epidemiologic studies of U.S. populations with a high burden of HIV infection: men who have sex with men (MSM), transgender women, and black/African American women (hereinafter African American men and women are referred to as blacks). An application may focus on one of these groups or may propose to enroll across the categories. It is not anticipated that a cohort will enroll only transgender women; however, transgender women are a particularly high-risk group and their inclusion is encouraged. Applicants are also encouraged to enroll young MSMs (age 13-34 years old, with emphasis on age 18 or younger), because this age group is at particularly high risk of HIV seroconversion. Applications should be structured around two phases. The UG3 (Phase 1) will be a two-year award to demonstrate enrollment of sufficient numbers of high-risk participants. Transition to the UH3 award (Phase 2) will be determined by an administrative scientific evaluation of Go/No-Go Transition Milestone accomplishment, preparedness of the cohort to implement the proposed epidemiology studies, programmatic priorities, and available funds. The UH3 phase of the project will provide support for an additional three years to conduct the epidemiologic research which will advance our knowledge of HIV transmission so that more effective prevention approaches can be elucidated.

There is a critical need to strengthen HIV prevention in the United States. While the HIV infection rate in the United States has declined modestly overall, progress has been uneven and rates have even risen among some subgroups. The advent of universal HIV treatment and roll-out of pre-exposure prophylaxis (PrEP) offer the opportunity that HIV transmission can be suppressed. However, challenges in uptake and adherence to prevention approaches remain. The ability to study recalcitrant hot-spots of transmission will require renewed focus and ever more precise prevention approaches. CDC data for 2014 show that approximately 80% of annual male HIV cases are among MSM. About 62% of annual cases in women are among black women. In 2014, the annual HIV incidence rates per 100,000 U.S. women were 1.7 for whites, 6.5 for Hispanic/Latina, and 30.0 for blacks. Among males, annual incidence rates per 100,000 were 12.6 for whites, 41.5 for Hispanics/Latinos, and 94.0 for blacks, with the highest infection rates among 13-34 year-old MSMs. Extremely high incidence rates have also been reported for male-to-female transgender populations. Epidemiologic studies within these high-risk populations are crucial for understanding the prevalence, incidence, and determinants of HIV infection to better design and target HIV prevention programs and services.

Following at risk individuals in the United States to study individual and contextual risk factors is challenging. First, research participants who have frequent in-person contact with health professionals adopt safer behaviors that make them less representative of the at risk populations from which they were drawn. In order to target prevention approaches to those at highest risk, it is necessary to develop methods to identify and study these individuals without altering their behavior and, thus, maximize the generalizability of the data obtained. Secondly, the subpopulations of persons at risk for HIV are imbedded within larger, demographically similar populations. For both MSMs and black women, focusing research to those at highest risk will require evaluation of both individual and external factors. In order to separate the relative contributions of individual and external factors in the setting of complex interactions, studies will require substantial numbers of event outcomes only achievable within large cohorts. Technology approaches that facilitate participation such that it is minimally invasive and that incentivize participation with nominal behavioral interference are the most promising ways to include these key populations and reduce bias.

Recent years have seen a surge in novel technology platforms and tools that can facilitate large-scale epidemiologic research. For example, the NIH Precision Medicine Initiative Cohort will study more than one million participants through a variety of methods including technologic approaches. Also the Army of Women study supported by the Avon Foundation is in the process of using the internet to identify one million women of different ages and ethnicities for recruitment in breast cancer research. The Black Women’s Health Study, supported by NIH, similarly follows 59,000 black women in the U.S. Technologies such as online surveys, smartphone apps, text messaging, and mobile video conferencing provide innovative new methods for active and passive data collection. The uptake of these technologies within the broader U.S. population as well as in target groups such as at risk MSM and black women has already been extensive. Rapid home-based HIV tests and sexually transmitted infection (STI) specimen collection also afford new opportunities for research.

Smart phones, the internet, and other technologies not only offer new approaches to track and gather information from diverse populations, but they have also changed the ways that people meet and interact. Epidemiology studies that use these technologies have the potential to identify hot-spots of HIV infection in the U.S. where HIV prevention programs could reduce transmission. Information is needed to inform HIV prevention programs and better tailor prevention messages to fit these U.S. subpopulations at greatest risk of infection, taking into account the thought processes, behaviors, and social contexts surrounding risky behavior. Real time assessment of risk and health seeking behaviors in populations large enough to find those at risk are now possible with these technologies. This initiative focuses on using these new technologies to study HIV risk behaviors and HIV seroconversions.

The primary goal of this FOA is to generate information needed to develop public health interventions to reduce HIV infections in the U.S. To do this, study teams must develop technology-focused approaches and demonstrate the capacity to enroll sufficient numbers of HIV-negative high-risk groups in the United States: black women, male-to-female transgender women and MSM, with an emphasis on those MSM at highest risk of seroconversion (black, Hispanic, or mixed race MSM, as well as those age 13-34 years, with emphasis on age 18 or younger). Enrollment success will be measured by the ability of the study to accrue large enough numbers of HIV seroconverters so that meaningful prevention research can be pursued. For example, the annual HIV incidence rate for primarily black women enrolled in the ISIS HPTN 064 study was 0.32%. Thus, to accrue 64 HIV seroconverters a year, assuming a comparable incidence rate, would require following 20,000 women. Studies that can successfully target a higher risk population may be able to accrue sufficient events in smaller cohorts, but it is anticipated that studies of HIV transmission in black women will need to be large, electronic, cost effective and efficient to be successful. Cohorts of MSM will also need to be large to allow for sufficiently detailed research to bring new understanding of the risk of transmission. However, because MSM incidence rates are higher, there is the potential to target MSM HIV seroconverters using smaller cohorts than those needed to study HIV transmission among black women. In the setting of the 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.

A secondary objective of this FOA is to facilitate interactions among awardees to share approaches, data, and methods, and to develop harmonization standards. Awardees must plan to attend meetings focused on cohort enrollment, study initiation and study results approximately at the start of years one, three and four, respectively.

Awardees are required to refer all subjects testing HIV-positive to treatment.

Studies of particular interest to NIAID and NIMH include:

• Identification of micro-epidemics in high HIV transmission areas (hot spots) and of key sub-populations where HIV prevention efforts are most needed.
• Characterization of subgroups of black women, transgender women, and MSMs who could be targeted for HIV prevention strategies.
• Descriptions of key HIV-related risk behaviors in U.S. hotspots and approaches to rapidly detect changes in these risk behaviors over time.
• Descriptions of risk behaviors that can inform interventions to reduce HIV incidence rates.
• Phylogenetic and epidemiologic analyses of HIV dynamics and models of transmission.
• Geospatial analyses of patterns of HIV infection in both rural and urban areas of the United States.
• 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 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 United States.
• Efforts targeting youth populations as outlined in this announcement.

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

• Clinic-based, surveillance-based or other studies of HIV-infected patients.
• Clinical trials.
• Studies of subjects residing outside the United States 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 centrally focused on the identification of predictors and correlates of HIV seroconversion among this FOA’s targeted key populations.
• Studies not focused on at least one of the high risk groups targeted by this FOA: black women, male-to-female transgender women, or MSMs, where at least half of planned MSM participants are self-identified as black, Hispanic, or of mixed race.

UG3/UH3 Phased Innovation Awards

This UG3/UH3 Phased Innovation Award has two phases: 1) UG3 award for milestone-driven studies to demonstrate enrollment of sufficient numbers of HIV-seroconverters, with a possible transition to 2) the UH3 award for epidemiologic research using the established risk cohort.

Applications must include a Go/No-Go Transition Milestone 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 have enrolled significant numbers of originally HIV-negative participants who become HIV-infected while under study. Continued programmatic priorities and availability of funds also 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 subjects to appropriate treatment centers.

Applicants are encouraged to visit the Frequently Asked Questions site at http://www.niaid.nih.gov/researchfunding/qa/Pages/RFA-AI-16-031.aspx.

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

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

Higher Education Institutions

• 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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

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

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

• 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).

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

The letter of intent should be sent to:

Peter Jackson, Ph.D.
Telephone: 240-669-5049
Fax: 301-480-2408
Email: pjackson@niaid.nih.gov

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

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

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

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

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

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

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

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

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

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

Specific Aims: 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.

Research Strategy: In preparing the application, investigators should consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application with regard to specific goals and the feasibility of each phase and the Go/No-Go transition milestone are critical. The Research Strategy should include:

• Separate sections that describe both the UG3 and the UH3 phases. It is not necessary to repeat information or details that are described in the UG3 section.
• A discussion of the significance of the proposed research to define HIV-negative subgroups in the U.S. at highest risk of HIV seroconversion.
• A description of the cohort enrollment and follow-up approaches and access to appropriate populations, including a discussion of their cost effectiveness, scalability, and how this approach will minimize barriers associated with bias and loss to follow-up.
• A description of the operational definition of retention in the study and methods to qualitatively evaluate and improve the recruitment and retention process during the UG3 phase to optimize the cohort composition.
• A description and justification for the target study population for the research question(s) posed. Include a discussion of generalizability of the study results, as well as a discussion of efforts that will be made to recruit adequate numbers of high-risk groups, including black women, transgender women, and/or black and Hispanic MSMs (at least half of the MSMs enrolled need to self-identify as Hispanic, black or of mixed race.)
• 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 verify the race, sex, and age of participants, including the strategy to be used to ensure that participants are discrete, not duplicated, individuals living in the United States.
• Plans to determine the HIV status of the cohort, both at enrollment and during follow-up. Include a description of the HIV testing methods to be used and appropriate validation plans. Applicants may propose to conduct screening programs for enrollment, or they may rely on clinic based test results or employ home-testing with participant photo submission of results as well as other mechanisms of self-report. Applicants are encouraged to explore the pros and cons of different approaches with respect to feasibility, cost, and veracity among other parameters.
• Plans for referring participants who seroconvert during the project for HIV treatment, including the care provider or providers to which they will be referred. Also include a description of how HIV-positive participants will be followed to obtain information on their subsequent treatment for HIV.
• If appropriate, a description of any additional considerations needed to enroll persons under age 18 years.
• 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 hypothesis to be tested in the UH3 phase of the study.
• Plans to assess 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 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 a clearly identified Go/No-Go transition milestone 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 milestone 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 a specific Go/No-Go transition milestone in the context of their proposed research and are not limited to this example:

The proposed study will enroll (fill in blank) number of MSMs of whom at least 50% will self-identify as black, Hispanic, or of mixed race. 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 HIV seroconverters by the end of Year 2.

Note: Applications lacking clearly described timelines for the UG3 and the UH3 phase, as well as the Go/No-Go Transition Milestone will be considered incomplete and will not be reviewed.

Protection of Human Subjects: 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: http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Pages/Protocol.aspx.

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, and 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, with the following modification:

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 LITE 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 the LITE research project. After all LITE awards have been made, the LITE Consortium will develop a unified policy for data and resource release, and the 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 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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

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

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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.

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

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

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

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

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?

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

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

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

Is there sufficient access to the appropriate population(s)? Are there appropriate methods of assessing the HIV exposure of the participants? Will the proposed research strategy lead to enrollment of adequate numbers of high-risk groups targeted by this FOA: (black women, transgender women, and/or black and Hispanic MSMs)? Is the strategy for verifying race, sex, and age of the participants appropriate? Does the application include an appropriate plan to insure that the cohort includes discrete, non-duplicated subjects living in the United States? 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?

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

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

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

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

For this FOA the committee will specifically evaluate: 1) if appropriate, a description of the ethical approaches to be used to enroll persons under age 18 years, 2) plans for referring participants who seroconvert during the project for HIV treatment, and 3) plans to protect the security of participants personally identifiable information.

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

Not Applicable

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

Applications will be assigned 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.

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

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

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

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

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

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

NIH reserves the right to negotiate the transition milestone with the applicants before making an award. The Go/No-Go criteria milestone for transition to the UH3 award will be referenced in the notice of award, and applicants must achieve their targeted numbers of HIV seroconverters by the end of Year 2 for the subsequent UH3 grant to be awarded. Achievement of the transition milestone (Go) will enable consideration for transition from the UG3 phase to the UH3 phase at the end of Year 2. Support for UG3 awards that do not meet their transition milestone (No-Go) will not continue. Appeals of the transition decision will not be accepted.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

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

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

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

• The planning, direction, and execution of the proposed research, including: definition of objectives and approaches; implementation; data management and analysis, interpretations and publication of results.
• Participating in the planning for meetings of the LITE award recipients, to focus on cohort enrollment, study initiation and study results;
• Referring all subjects testing HIV-positive to treatment. Information about referral efforts and the treatment status of all subjects 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 (black women, transgender women and/or MSM, at least half of whom are minority), 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 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 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 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 datasets for all approved internal and external research collaborators;
• Provide input and generate research presentations and publications of LITE 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.

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

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

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

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

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

Cynthia Rodriguez
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5391
Email: cynthia.rodriguez@nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: siscor@mail.nih.gov

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clark1@mail.nih.gov

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

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