It is critical that applicants follow the instructions in the Research Instructions for 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

This Funding Opportunity Announcement (FOA) is a new initiative to support the development of highly innovative, highly relevant and high priority HIV/AIDS and alcohol research as outlined in the NIH Notice NOT-OD-15-137. This research should be suitable for advancing the translation of basic biological and behavioral science research into clinical practice through improved interventions for prevention and treatment among individuals living with HIV. Specifically, this FOA solicits applications for projects to adapt, apply, and validate existing or emerging behavioral and/or biological technologies into a new generation of patient-focused interventions to improve the treatment of alcohol-related problems among individuals living with HIV. The goal of this announcement is to provide resources for two phases of highly innovative research. The first phase focuses on testing promising hypothesis-driven research on the behavioral/and or biological mechanisms underlying increased morbidity and mortality among HIV+ alcohol users with the goal of developing and pilot testing innovative new methods of measurement and/or interventions. The second phase aims to pilot test these new informative approaches. This translational research framework is intended to provide short-term funding for promising behavioral and biological research that focuses on illuminating the pathophysiology of alcohol use and alcohol-related comorbidities among HIV+ individuals with significant current and past drinking histories. This research is intended to inform clinical decision making at the individual and operational level so that this basic research may be translated into practice.

A continuum of severity of alcohol use, including harmful and hazardous use, and identification of alcohol use disorders (AUD) are common among individuals living with HIV. Past and present alcohol consumption influences HIV disease progression and survival directly by altering timing, adherence, and response to antiretroviral treatment(s). It also influences patient outcomes by increasing risk for and progression of HIV and antiretroviral associated comorbidities, including: liver disease, cardiovascular and cerebrovascular disease, pulmonary disease, bone disease, and cancer. Individuals living with HIV have a lower tolerance for alcohol and alcohol use among HIV+ individuals has a greater impact on their health outcomes, including increased mortality and frailty. Despite this, individuals living with HIV often maintain heavy levels of alcohol consumption as they age and often substitute continued alcohol use for other substance use.

The cumulative impact of patterns of past and current alcohol consumption is likely to increase now that individuals living with HIV are expected to live 20-30 years or longer on antiretroviral therapy. Thus reducing the interactions of alcohol with these medications and associated comorbidities is also of increasing importance. It is critical that individuals aging with HIV, and those with both HIV and associated comorbidities, have coordinated treatment that takes into consideration the context of past and current alcohol use and its consequences for increased morbidity and mortality.

Alcohol use in the context of HIV and other associated comorbidities has been shown to be a modifiable factor which plays a critical role in both biological and behavioral health outcomes.

There is much that can be done to mitigate the harmful effects of alcohol. A growing body of research has demonstrated that behavioral and pharmacologic interventions for alcohol can be implemented successfully in primary care and office-based settings and through electronically enhanced mobile interventions. However, to accomplish this, we must adapt and coordinate behavioral and pharmacologic interventions to the complex ecological and clinical context of HIV infection, identifying critical access points for delivery and maintenance of interventions.

Traditionally, translational science has focused on the research bridge of basic science and clinical care or the bridge between clinical care and the community. However, alcohol use, its settings, prevention, and treatment have a significant (and complex) effect on the prevention and treatment of HIV/AIDs and the translation of these research findings has been challenging. Still, it is imperative that current efforts to reduce or eliminate new HIV infections do so in a variety of settings that include the consumption of alcohol.

This announcement expands exploratory research to link alcohol use's effects at individual, group, and population levels to high priority topics that are being supported for continued HIV funding to strengthen the understanding of the role of alcohol in these areas and to improve translational research. This translational research will ultimately inform the development of precision medicine for HIV+ individuals who have past and/or current histories of drinking.

Projects proposed in response to this FOA will require multidisciplinary efforts to succeed and therefore all applicant teams must include expertise in both HIV and alcohol research and where appropriate (bench to bedside/engineering/bioassay/behavioral assessment/treatment development), and healthcare delivery where appropriate (bedside to community).

High Priority Topics of Research (for support using AIDS-designated funds)

Areas of study include the measurement of alcohol use's effects and identification of mechanisms related to HIV outcomes. In particular, those related to the impact of alcohol at all levels of consumption resulting in persistent inflammation in the context of varying levels of adherence and response to antiretroviral medication(s) and how these patterns of behavior and response to HIV management over the lifespan lead to higher levels of morbidity and mortality. In addition, this initiative aims to increase information about the intervention and treatment of alcohol associated pathophysiology in the context of important comorbidities. Alcohol use has been shown to impact care seeking, entry into care, and retention in care. Development of a clear understanding of these processes in diverse systems of care needs to be obtained in order to promote effective intervention(s) in multiple contexts.

Research may be carried out in either domestic or international settings with populations highly impacted by HIV/AIDS and alcohol use. Continued research will inform the application(s) of precision medicine in a variety of domains and ultimately result in improved guidelines for intervention among individuals living with HIV who have past and/or current drinking histories. All research must reflect the high priority areas outlined below.

Focus on translational research that will advance the role of precision medicine in high priority areas for HIV+ individuals who drink. These include the impact of alcohol use, settings and situations for alcohol use, and comorbidities associated with alcohol use among HIV+ individuals. The overarching goal is to reduce the incidence and/or prevalence of HIV infection among individuals who drink and the morbidity and mortality over the life course. One goal of this announcement is to further the development of informative indicators of health among HIV+ individuals who currently drink or have had pathophysiology associated with past drinking (e.g. liver disease, neurocognitive deficits, microbial translocation) that may impact the course of HIV treatment and its impact on morbidity and mortality at the individual, group, and population level.

Precision Medicine for HIV+ Alcohol Users refers to the tailoring of medical treatment in a number of potential contexts to the individual characteristics of each individual who share these and other associated comorbidities. The primary goal will be to advance the formulation and application of clinical information, raise awareness among patients, and train treatment providers for the better detection and intervention with these subpopulations. The term Precision Medicine does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to HIV disease in the context of significant past and/or current alcohol use, in the biology and/or prognosis of those disease outcomes they may exhibit, or in their response to a specific intervention/treatment. However improvement through the use of new technologies may result in improvements in the application of precision medicine for HIV+/Alcohol users (e.g. biosensors, inflammatory markers). Preventive or therapeutic interventions can then be concentrated on those individuals will benefit the most, sparing expense and side effects for those who will not.

Impact of alcohol use in the context of HIV epidemic for individuals who have significant past or current histories of drinking that may have resulted in organ and tissue damage or changes in behavior related to self-care, adherence, or risk taking.

High Priority Research Areas Include:

• Reducing Incidence of HIV/AIDS including:
• Developing and testing promising vaccines
• Developing and testing microbicide(s) and pre-exposure prophylaxis candidate(s) and methods of delivery, especially those that mitigate adherence issues; and developing, testing, and implementing strategies to improve HIV testing and entry into prevention services.
• Next generation of HIV therapies with better safety and ease of use including:
• Developing and testing HIV treatments that are less toxic, longer acting, have fewer side effects and complications, and easier to take and adhere to than current regimens.
• Implementation research to ensure initiation of treatment as soon as diagnosis has been made, retention and engagement in these services, and achievement and maintenance of optimal prevention and treatment responses.
• Research toward a cure including:
• Developing novel approaches and strategies to identify and eliminate viral reservoirs that could lead toward a cure or lifelong remission of HIV infection, including studies of viral persistence, latency, reactivation, and eradication.
• HIV-associated comorbidities, coinfections, and complications including:
• Addressing the impact of HIV-associated comorbidities, including tuberculosis, malignancies; cardiovascular, neurological, and metabolic complications; and premature aging associated with long-term HIV disease and antiretroviral therapy.
• Basic Research, including:
• Understanding the basic biology of HIV transmission and pathogenesis; immune dysfunction and chronic inflammation; host microbiome and genetic determinants; and other fundamental issues that underpin the development of high priority HIV prevention, cure, co-morbidities, and treatment strategies.

Examples of Innovative Translational Research could include but are not limited to:

• Identification of informative new indicators of disease progression related to inflammation and/or microbial translocation by banking and analysis of multiple serological specimens from a variety of available specimen repositories and expanding the analysis of these specimens to be more informative in clinical decision making by providers and patients.
• Carrying out formative work in unique populations with high rates of infection related to alcohol use and/or alcohol use settings that are the result of complex social interactions and networks. Identifying how healthcare providers could better identify and use these social networks to access individuals and retain them in care.
• Developing a framework for testing and evaluating the impact of alcohol use on emerging pharmacological products for the prevention of acquisition and transmission of HIV (e.g., vaccines, microbicides, PrEP) and to examine these toxicities as products emerge.
• Identification of optimal treatment regimens related to different patterns of drinking over the life span by developing advanced analytic techniques to take into account developmentally appropriate time sensitive covariates.
• Understanding the impact of alcohol on barriers in the gut, liver, and brain on facilitating the establishment of viral reservoirs and the use of alcohol treatment pharmacotherapies and its impact on activating viral reservoirs.
• Study the feasibility of assessing the convergence of multiple brain imaging technologies with mapping techniques that are associated with cognitive dysfunction for both alcohol and HIV and measurement of a variety of informative clinical markers associated with progressive functional impairment Developing easy-to-use monitors of alcohol use and analysis of patterns of use in a broad range of hard-to-reach populations at risk for or infected with HIV. Improving access and engagement in care for these populations (e.g., run away and homeless youth, HIV+ youth not in care, HIV+ pregnant women, etc.).

This announcement proposes to use a unique mechanism to encourage collaboration between diverse researchers to develop innovative collaborations between investigators in a number of areas through shared short term activities focused on the innovativeness of the proposed research and to demonstrate a high-level of collaborations and feasibility for advancing high-priority HIV and Alcohol research.

Two-phase Projects: Investigators responding to this FOA must address plans for both UH2 and UH3 phases.

• The UH2 phase of this FOA support the testing of novel hypotheses related to identification and testing of the impact of alcohol on high-priority HIV/AIDS (see NOT-OD-15-137) HIV basic behavioral or biological hypotheses that may be translated into pilot interventions in the UH3 phase. These interventions may include translational research related to the bench to bedside or bedside to community. Evidence for testable preintervention hypotheses need to be validated. Testable translational hypotheses that must achieve preliminary validation within two years before any clinical or community intervention-focused research may be implemented. The feasibility for the use of any associated technology for the implementation of the research should be demonstrated within the UH2 phase and available (e.g., transdermal sensors, transcranial stimulation, eHealth applications, specialized blood assays, etc.) when proposing UH3 continuation of the application. Any new assays (e.g., biomarkers for alcohol and/or HIV associated control) must meet the standards for analytical validation before they may proceed to the UH3 phase. Collaboration with commercial entities that may ultimately distribute or otherwise support successful interventions and associated technology is encouraged but not necessary for a successful application.
• The UH3 phase of this FOA supports the clinical and or community validation of translational preintervention research. Support may be sought to obtain retrospective or prospective specimens from NIAAA-supported or other clinical trial if required. UH3 phase of the applications (e.g., studies of controlling alcohol-related inflammation, social network modifications, etc.) will be a) evaluated in the initial review process and b) after the completion of the UH2 phase in order to proceed to the UH3 phase of research.

Two-phase Projects: Initial cooperative agreement awards for up to 2 years will be granted for validation of the translational hypotheses in the UH2 phase. If the project meets the aims described for the UH2 phase, then the project will proceed to the UH3 phase pending administrative review and availability of funds as described below.

Objectives for the UH2 Hypothesis Testing Preintervention Phase: During the UH2 phase, the investigators must complete preliminary validation of their hypotheses. Since this is likely not to require large numbers of subjects and/or samples, the investigators are expected to provide samples that are appropriate for the clinical or community context of the intended intervention. Expectations for the UH2 Validation phase include determining the following design characteristics:

• Measurement accuracy for alcohol use and HIV outcomes
• Changes in target behaviors and/or pathophysiuology
• Analytical specificity including identification of cofactors/covariates
• Reportable range of clinically significant test results
• Harmonization of meausres if the research is to be carried out in multiple samples in multiple locations
• Establishment of appropriate quality control and improvement procedures for proposed interventions
• Any other performance characteristic required for hypothesis testing with determination of calibration and control procedures.

Transition from UH2 to UH3: After administrative review by NIAAA program staff, successful UH2 projects will be prioritized for selection and transition to the UH3 phase.

Objectives for the UH3 Validation Phase: The UH3 phase will complete the clinical and or community validation of the intervention and prepare potential use in more extensive trials or implementation in broader context.

Expected outcomes of the UH3 phase that should be met by each project:

• Demonstration of the association of the result of proposed intervention with a clinically meaningful endpoint in the prevention or treatment for prevention in the control or eradication of HIV (e.g., survival, response, disease presence or absence) in samples from patients or communities that have been treated or exposed to a uniform intervention or observation for treatment, prevention or alcohol/HIV interventions
• Within trials of pharmacological agents the estimation of the prevalence of the marker within subjects or patients for the intended clinical context
• Establishment of an appropriate cut-off or threshold for the assay or screening or assessment technology using appropriate statistical analysis

Applications that propose trials that assess the clinical/community utility of an existing intervention but is intended to develop new hypothesis driven interventions are not responsive to this FOA.

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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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).

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow the instructions in the Research Instructions for 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:

Dr. Abraham P. Bautista
Telephone: 301-443-9737
Fax: 301-443-6077
Email: [email protected]

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:

Specific aims should be submitted for each phase.

Research Strategy:

Approach must be divided into two parts corresponding to the UH2 and UH3 phases. The UH2 must include plans on how to accurately measure alcohol use, HIV outcomes & pathophysiology, target behaviors, analysis of the specificity in identifying cofactors/covariates, establishment of quality control and improvement procedures for interventions. The UH3 validation phase must describe the association of the result of proposed intervention with a clinically meaningful endpoint in the prevention or treatment for prevention in the control or eradication of HIV (e.g., survival, response, disease presence or absence) in samples from patients or communities that have been treated or exposed to a uniform intervention or observation for treatment, prevention or alcohol/HIV interventions. It must also describe a plan on how to estimate the prevalence of the markers within subjects or patients for the intended clinical context and the appropriate cut-off or threshold for the assay or screening or assessment technology using appropriate statistical analysis.

Milestones and Timeline

A timeline (Gantt chart) including milestones is required. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative objective criteria for success. Yearly quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones: e.g., appropriate objective performance targets, quantitative for go/no go decision points such as an appropriate level of detection and coefficient of variation, or sensitivity and specificity; and timelines for assessing progress in both the UH2 and UH3 phases, including specific milestones for progressing from the UH2 phase to the UH3 phase. Milestones and timelines for each stage must be provided in a separate heading at the end of the Approach section for each UH2 and UH3 subsection, and should:

• Provide appropriately detailed (quantitative) criteria by which milestone achievement will be assessed.
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
• Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NIAAA Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

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

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

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

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

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?

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?

Specific for this FOA: In the UH2, How well considered is the plan to accurately measure alcohol use, HIV outcomes & pathophysiology, target behaviors, analysis of the specificity in identifying cofactors/covariates, establishment of quality control and improvement procedures for interventions? Does the UH3 validation phase appropriately describe the association of the result of proposed intervention with a clinically meaningful endpoint in the prevention or treatment for prevention in the control or eradication of HIV (e.g., survival, response, disease presence or absence) in samples from patients or communities that have been treated or exposed to a uniform intervention or observation for treatment, prevention or alcohol/HIV interventions. How well is the plan described in estimating the prevalence of the markers within subjects or patients for the intended clinical context and the appropriate cut-off or threshold for the assay or screening or assessment technology using appropriate statistical analysis? How well are the milestones and timeline described? Are the milestones realistic, indicating a successful UH2 phase?

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

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

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 on Alcohol Abuse and Alcoholism, 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:

• 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.
• 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 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 Council on Alcohol Abuse and Alcoholism 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.

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.

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

• 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.
• Awardees will regularly provide updates, progress, new/pending publications, new development and changes in future plans to the NIAAA Scientific Collaborator.
• Coordinate a regular schedule of meetings with NIAAA Project Collaborator for review and consultation.
• Coordinate project activities with their institutions, with collaborators, and with the NIAAA Project Collaborator.
• Accept assistance and seek input from NIAAA Project Collaborator to inform the pursuit of project goals.
• PD(s)/PI(s) will publish and publicly present and disseminate results of the research project.

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

• NIAAA Project Collaborator: A designated NIAAA Program Director, acting as a Project Collaborator, will have substantial programmatic involvement, as described below.
• The NIAAA Project Collaborator will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is essential, these individuals will seek NIAAA waiver according to the NIAAA procedures for management of conflict of interest.
• Coordinate and facilitate the interactions among the UH2/UH3 awardees under this initiative;
• Serve as liaison between the research awardees and NIAAA staff members and investigators involved in the program, facilitating interactions and scientific integration between the UH2/UH3 awardees;
• Promote and help coordinate collaborative research efforts that involve interactions with other NIAAA-sponsored programs, projects, and centers;
• Participate in program meetings;
• Review all major transitional changes that the awardees might propose (e.g., a change in partnering institution) and advice on their appropriateness prior to implementation to assure consistency with the goals of this FOA;
• Provide technical assistance and advice to the awardees as appropriate;
• Assist in the interaction between the UH2/UH3 Research awardees and investigators at other institutions, as appropriate for the program;
• Assist in avoiding unwarranted duplication of effort with other NIH efforts;
• Monitor institutional commitments and resources to the awardees;
• Suggest reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- Specifically, the NIAAA Project Collaborator may recommend withholding of support, suspension, or termination of a UH2/UH3 award for lack of adherence to required policies and/or procedures;
• Develop working groups and trans-project efforts as needed; and
• Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the awardees.

NIAAA Program Official: NIAAA Program Director, acting as the Program Official, will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice.

Areas of Joint Responsibility include:

The PD(s)/PI(s) and the NIAAA Staff Collaborator will participate in regularly scheduled quarterly Steering Committee meetings to coordinate implementation and evaluation of the ongoing projects. The Steering Committee will consist of a minimum of one member from each participating site and the NIAAA Staff Collaborator. Every participating site and the NIAAA Staff Collaborator will each have a single vote on the Steering Committee. All Steering Committee decisions and recommendations that require voting, will be based on a majority vote. Additionally, the PIs and the NIAAA Staff Collaborator will participate in a yearly meeting/workshop to present major findings, to plan collaborative efforts, to assist in analysis, interpretation, and dissemination of scientific findings.

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

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

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

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

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.

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Kendall J. Bryant, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-0332
Email: [email protected]

Ranga Srinivas, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-2067
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

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.