Department of Health and Human Services
Part 1. Overview Information


Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Funding Opportunity Title

Medications Development for the Treatment of Alcohol Use Disorder (U01 Clinical Trial Optional)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type


Related Notices
  • November 15, 2018 - This RFA has been reissued as RFA-AA-19-005.
Funding Opportunity Announcement (FOA) Number


Companion Funding Opportunity


Catalog of Federal Domestic Assistance (CFDA) Number(s)


Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to invite cooperative agreement applications for research that advances promising compounds thorough the drug development pipeline for the treatment of Alcohol Use Disorder (AUD).

NIAAA is seeking applications for medications development research projects from both for-profit and not-for-profit entities, including academic institutions, pharmaceutical and biotechnology companies, private and public foundations, small businesses not eligible for the SBIR/STTR program and single entities able to demonstrate significant resource commitment to the proposed project. A resource commitment from a single entity could, for example, consist of salary support for key personnel or production and formulation of clinical trial material.

The aim of this FOA is to move candidate compounds through Investigational New Drug (IND) requirements, Phase 1 human safety, tolerability, and dosing studies, and Phase 2 human laboratory and proof-of-concept trials. Within these phases of drug development, each proposed project should have a defined entry and exit point.  Finally, this FOA will not support animal studies to prove efficacy of the candidate compound unless required by the Food and Drug Administration or peer review. Applicants are strongly encouraged to contact the NIAAA Division of Medications Development Staff prior to submitting to this FOA.  

Key Dates


Posted Date

January 18, 2018

Open Date (Earliest Submission Date)

February 20, 2018

Letter of Intent Due Date(s)

February 20, 2018

Application Due Date(s)

March 20, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May-June, 2018

Advisory Council Review

August 2018

Earliest Start Date

September 2018

Expiration Date

March 21 , 2018

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Table of Contents

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

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Alcohol Use Disorder is a global health problem, affecting more than 78 million adults world-wide, including over 15 million adult Americans and resulting in a myriad of medical, psychological, social, economic, and personal problems. AUD ranks among the leading causes of decreased disability-adjusted life-years and ranks third in preventable causes of death in the United States. The total economic cost to society in the United States is a staggering $249 billion each year.

During the past two decades, progress has been made in developing medications to treat AUD. Currently, there are three Food and Drug Administration (FDA)-approved medications for the treatment of alcohol dependence: disulfiram, oral and long-term injectable naltrexone, and acamprosate. In addition, nalmefene recently has been approved in Europe. However, given the heterogeneous nature of AUD, many individuals show only limited or no response to these medications. Because of this, developing and evaluating new, more efficacious and safe medications remains a top priority for NIAAA.

The purpose of this FOA is accelerate the pace of grant-funded medications development for AUD by focusing on moving candidate compounds through the drug development pipeline. This will be accomplished by using a cooperative agreement between NIAAA and outside entities to include both profit and non-profit organizations.

Applications can focus at any point along the drug development pipeline, including: pre-clinical investigational new drug (IND)-enabling studies (e.g., clinical toxicology, Good Manufacturing Practice (GMP) manufacturing, and pharmacokinetics); Phase 1 human studies (e.g., safety, tolerability, dosing, alcohol interaction); and Phase 2 studies (i.e., proof-of-concept human laboratory and clinical trials) of either a new chemical entity or an already marketed therapeutic compound. IND-enabling and Phase 1 studies should be conducted consistent with FDA guidelines (

The defined entry and exit points along the drug development pipeline will depend on the developmental status of the candidate compound. For example, some candidate compounds may only need a few IND-required studies, while other compounds may have already completed the IND requirements and can start the Phase 2 trials.

NIAAA is interested in exploring new targets for medications development. With our increased understanding of biological mechanisms underlying AUD, more than 35 promising targets have been shown to alter alcohol drinking behavior. The targets that are of particular interest to NIAAA are as follows: vasopressin 1b antagonist, hypocretin (orexin) receptor antagonist, nociception/orphanin FQ (NOP) receptor agonist/antagonist, kappa opioid receptor antagonist, Corticotropin releasing factor (CRF)1 antagonist, glucocorticoid receptor antagonist, metabotropic glutamate receptor type 5 antagonist and type 2/3 agonist, glutamate NMDA modulator, glutamate transporter 1 enhancer, AMPA/kainate antagonist, fatty acid amide hydrolase (FAAH) inhibitor, monoacylglycerol lipase (MAGL) inhibitor, potassium channel activator, nicotinic a3ß4 partial agonist and a7 agonist/positive allosteric modulator, phosphodiesterase inhibitor, GABAB receptor positive allosteric in modulator, GABAA receptor modulator, glucagon-like peptide 1 (GLP-1) agonist, rapamycin complex 1 (mTORC1) inhibitor, ghrelin receptor (GHS-R1A) antagonist, sigma receptor antagonist, neuropeptide S agonist/antagonist, pannex-1 channel blocker, PPARa agonist, PPAR¥ agonist, and monoamine stabilizer. Other targets also will be considered if they have been shown to alter alcohol drinking behavior in animal models. Exploration of new types of candidate compounds addressing these targets, both novel and repurposed compounds, is a high priority.

Medications that have been extensively investigated are no longer a priority. These include, but are not limited to, naltrexone, acamprosate, topiramate, and ondansetron. Applicants are strongly encouraged to contact the NIAAA Division of Medications Development Staff prior to submitting to this FOA. 

In addition to focusing on individuals with AUD only, development of effective pharmacologic treatments for individuals with co-occurring psychiatric disorders, especially post-traumatic stress disorder (PTSD), is a high priority for NIAAA. Compared with non-comorbid individuals, people with comorbid disorders tend to have a more severe clinical impairment, higher rate of psychosocial and medical problems, higher utilization of health service, higher suicide rate, and lower quality of life.

Entry Criteria:

Applicants who propose candidate compounds need to minimally satisfy the following conditions:

1) The candidate compound must be adequately characterized (e.g., structure/identity, selectivity,

    other modality-specific characteristics).

2) The candidate compound should have demonstrated efficacy in animal model(s).

    NIAAA is interested in studies from the following stages of drug development:

Examples of studies that can be proposed for each stage of medications development include but are not limited to:

A. Pre-Clinical IND-Enabling Studies

1) Toxicology (acute and repeated dose) and if applicable, genotoxicity, carcinogenicity, reproduction,    and immunotoxicity studies.

2) Pharmacokinetics (absorption, distribution, metabolism, and excretion [ADME])

3) Formulation development and chemical synthesis under GMP

4) Additional efficacy studies if required by FDA or peer review

5) Medicinal chemistry studies to further optimization if the candifsate compound

B. Human Phase 1 Studies

1) Pharmacokinetics (ADME)

2) Single and multiple ascending dosing

3) Pharmacodynamics

4) Target engagement

5) If applicable, alcohol interaction

6) If applicable, abuse liability

C. Human Phase 2 Studies (with patient population)

1) Human laboratory trials

2) Proof-of-concept clinical trials


Delineation of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.  Milestones are to be performance-based to achieve completion of the study on time and on budget. Investigators should design a series of milestones for completion of the study and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones. Investigators should design relevant milestones that reflect essential progress of the proposed research, and should determine dates at which the study will have achieved targeted accrual at predefined increments.

Continuation of the award is conditional upon satisfactory progress and subject to availability of funds. If, at any time, progress falls significantly below the projected milestones, the NIAAA will consider ending support and negotiating an orderly phase-out of the award and retains, as an option, periodic external peer review of progress. NIAAA staff will closely monitor progress at all stages, milestones, accrual, and safety.

Special Considerations

Before Phase 2 human studies can be conducted, an IND or IND exemption must be obtained. In some cases, a pre-IND meeting with the FDA may be needed. In conducting Phase 2 human studies, NIAAA encourages data collection assessments capturing demographics, daily drinking (before and during treatment), AUD diagnosis (and/or characterization of problematic drinking), alcohol craving, alcohol-related consequences, comorbidities (i.e., substance use, medical, psychiatric), medication adherence, and potential mechanisms and moderators of treatment effect. 

It is expected that applicants will be attentive to NIH policies related to Rigor and Reproducibility.

Medications development research in minority and underserved populations (e.g., African Americans, Asians, Hispanics, Native Americans, Alaska Natives, Native Hawaiians, Pacific Islanders) is sparse. Thus, investigators are encouraged to include these populations in their medications development clinical studies in sufficient numbers to determine whether there are unique circumstances that should be considered in future research.

NIAAA will not accept AIDS-research related applications in response to this FOA.

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

Section II. Award Information
Funding Instrument

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

Application Types Allowed

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Clinical Trial?

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

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIH intends to fund an estimate of 4 awards, corresponding to a total of $3.0 M, for fiscal year 2018. Future year amounts will depend on annual appropriations.

Award Budget

Budgets must not exceed $1.0 M direct costs per year for IND enabling studies and $500,000 direct cost for Phase 2 human laboratory and proof-of-concept clinical trials may be requested.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.     

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

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)


  • 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


  • 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)
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.

Required Registrations

Applicant Organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (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 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.
  • – Applicants must have an active DUNS number and SAM registration in order to complete the registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

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

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

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.

2. Content and Form of Application Submission

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

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Dr. Abraham Bautista
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-9737

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed. In addition, the following should be considered:

Facilities & Other Resources: The application must describe in detail how the funds requested to NIAAA will be leveraged with current resources. It should include all the strengths and resources that the grantee organization and, if pertinent, its collaborators will be contributing towards accomplishing the research plan.

For applications which propose a grantee and one or more collaborating organization(s), the application should contain a specific description of each resource, how it will facilitate the project goals, and an outline of the projected timeline for resource receipt and utilization. The resources provided by the collaborating organization(s) should represent a significant contribution to the project.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: The Research Strategy section should include the following subsections:

A. Significance: Clinical Impact and Feasibility
B. Supporting Data for Entry
C. Detailed Plans for Approach (Including Milestones and Timelines)
D. Intellectual Property (IP) Strategy

A. Significance

Clinical Impact and Feasibility:

  • If the therapy is an improvement over an earlier generation agent(s) that has not been marketed, discuss what advantages the new agent has. Include results from previous clinical trials with related agents.
  • Discuss how the proposed project relates to therapy development efforts underway in academia and industry, regardless of therapeutic class.  What are the distinct advantages to the new, proposed therapy considering other investigational agents that might be entering the clinical pipeline soon?
  • Briefly outline the plans for the first clinical proof-of-concept study  and comment on feasibility of conducting the trial(s).

B. Supporting Data for Entry

The Supporting Data for Entry section contains, but is not limited to, comprehensive data to justify that the application meets the entry criteria, as well as data that demonstrate the feasibility of conducting studies to address the specific aims, for example:

(1) Describe what is known about the candidate compound such as structure/identity, selectivity/specificity, bioactivity, stability, bioavailability, and other modality- specific characteristics.

  • Demonstrate selectivity/specificity
  • Describe bioactivities of the candidate compound in vitro (e.g., binding affinities, IC50 in relevant in vitro model). Show evidence that the candidate modulates the targets or pathway in vitro.

(2) Present data showing the minimal effective dose, optimal effective dose, time and duration of treatment. These should have been determined in relevant in vivo assays using clinically relevant functional and/or anatomical outcome measures, and/or in vivo target engagement assays, using a candidate that is sufficiently pure. [This normally should have been done using the clinically intended route of administration and special formulations if proposed (such as slow release, liposomes, nanoparticles, etc.), unless justified to use other routes of administration in which case the dose-response must have been reliably bridged by pharmacokinetics measurements]. Present data on pharmacokinetics, CNS penetration (if applicable), and pharmacokinetics-pharmacodynamics relationship. NIAAA encourages discussion of rigor, control of bias, and transparency of reporting in order to ensure robustness and reproducibility of the observed results.

  • Describe bioavailability; include data and analyses performed to demonstrate the candidate compound can penetrate the blood-brain-barrier, if required for efficacy.
  • When interpreting the results, consider alternative interpretations of the experimental data, relevant literature in support of or in disagreement with the results, and include discussion of effect size in relation to potential clinical impact.
  • Applicants should explain what key data, if any, has been reproduced, by the applicants or by independent investigators.

(3) Discuss feasibility of production and reproducibility of production of the candidate.

C. Detailed Plans for Approach (Including Milestones)

In this section applicants should detail the planned approach. Describe milestones to be used for measuring success in achieving each of the research plan's objectives.  One or more milestone should be used for each objective. For each milestone provide details on methods, assumptions, experimental designs, and data analysis plans (if the results are quantitatively measured). Specify the quantitative criteria for measuring success and the rationale for the quantitative criteria. Quantitative criteria should be robust and be consistent with the state-of-the-art in the field. Most of the time the quantitative criteria for success in the milestones will also be used for making go/no-go decisions and this should be specified. There should be at least one milestone proposed for completion at the end of each year.

Approach could include but is not limited to:

  • Describe experimental design. If the studies proposed are planned to be done in a Contract Research Organization (CRO), Contract Manufacturing Organizations (CMO), list the name(s) of the CRO(s) for the activities.
  • Present a plan for the preparatory work for IND-enabling studies such as Chemistry, Manufacturing, and Controls (CMC) activities, preliminary safety studies, validation of target engagement assays to support future human clinical trials, final characterization of the manufactured material intended for preclinical IND-enabling toxicology studies, etc.
  • Present a plan for preclinical studies that are consistent with or per regulatory guidance will be achieved. These include IND-enabling toxicology, tumorigenicity evaluations as needed, immunogenicity evaluations as needed, biodistribution studies as needed, large animal study to assess biocompatibility of means of clinical delivery of the candidate, validation of appropriate assays for target engagement markers to enable human use, etc.
  • For critical preclinical studies, like definitive verification of the activities of the candidate (if needed) in preclinical efficacy studies, and/or pharmacokinetics-pharmacodynamics studies, provide the following:
  • The choice of models, assays, and clinically-relevant endpoints (primary, secondary, and exploratory when applicable) for these studies;
  • Information on study design, power analyses and associated assumptions for sample size estimation (e.g., what is considered a minimal change predictive of clinically meaningful change, variance known in the in vivo assay described in supporting data, expected treatment effect size), and detailed procedures of how blinding and randomization will be done;
  • Data handling rules such as criteria for inclusion and exclusion of data;
  • Plans for data analysis and interpretation;
  • Outline any differences between how these analyses will be performed and those used to develop the Entry Criteria (outlined above) for the candidate.  Provide a rationale for any changes.

D. Intellectual Property Strategy

Applicants should describe the IP landscape surrounding their therapy. Applicants should describe any known constraints that could impede the development of their therapy (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed.  If the applicant proposes using an agent(s) whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any questions of freedom to develop consistent with achieving the goals of the program. Applicants should include a letter (see Letters of Support) from the entity who owns the IP indicating whether they will provide the agent(s), if there are any limitations on the studies that can be performed with that agent(s), agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the therapy being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated United States Patent and Trademark Office (USPTO) database links, if applicable.

Applicants should discuss future IP filing plans. For a multiple PD/PI, multi-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if there are multiple PD/PIs and institutions involved, as appropriate and consistent with achieving the goals of the program.

Letters of Support: Applicants should include letters of support from consultants, contractors, and collaborators.

If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.

If collaborating with a private entity, include a letter of support that addresses any agreement to provide agent(s), any limits on the studies that can be performed with said agent(s), any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place.  This letter should come from a high official within the private entity who has authority to speak on these issues.

The proposed resources (e.g., funds, personnel power, materials, in-kind resources) are expected to provide a significant contribution to the project.

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.


Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

Organizations must submit applications to (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 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 on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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 when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

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

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process. 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.

In addition, for applications involving clinical trials

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

Overall Impact

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

Scored Review Criteria

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


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?

In addition, for applications involving clinical trials

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

Did the PD/PI describe the Clinical Impact and Feasibility of the agent?  If the therapy is an improvement over an earlier generation agent(s) that has not been marketed, what advantages does the new agent have? Are previous clinical trials with related agents provided and discussed? Did the PD/PI discuss how the proposed project relates to therapy development efforts underway in academia and industry, regardless of therapeutic class?  Are the plans outlined for the first clinical proof-of-concept study and feasibility of conducting the trial(s) discussed? 


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

In addition, for applications involving clinical trials

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


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? 

In addition, for applications involving clinical trials

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


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? 

Did the study meets the entry criteria, including a) compound structure/identity, selectivity/specificity, bioactivity, stability, bioavailability, and other modality specific characteristics; and b) demonstrated efficacy in animal model(s)?

Was the feasibility of production and reproducibility of production of the candidate compound discussed? Is there a description of milestones that will be used for measuring success in achieving each of the research plan's objectives?  Did the PD/PI describe quantitative criteria for measuring success? If applicable, was a description provided of the Contract Research Organization (CRO) and/or Contract Manufacturing Organizations (CMO), including their proposed activities for the ? Are preclinical studies described consistent with or per regulatory guidance including IND-enabling toxicology, tumorigenicity evaluations as needed, immunogenicity evaluations as needed, biodistribution studies as needed, large animal study to assess biocompatibility of means of clinical delivery of the candidate, validation of appropriate assays for target engagement markers to enable human use, etc?

Regarding the Section on Entry Criteria:

Is the candidate compound adequately characterized (e.g., structure/identity, selectivity, and other modality-specific characteristics)? Has the candidate compound demonstrated efficacy in animal model(s)?

Regarding the Section on Milestones:

Are the milestones robust and associated with clear, quantitative criteria for success that allow go/no go decisions, is it justifiable? Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?

Specific to applications proposing clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

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

Data Management and Statistical Analysis

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

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?  


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

In addition, for applications involving clinical trials

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

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

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

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

Additional Review Criteria

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

Study Timeline

  In addition, for applications involving clinical trials

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

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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.

Inclusion of Women, Minorities, and Children 

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.

Vertebrate Animals

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


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

Additional Review Considerations

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

Intellectual Property 

If applicable the reviewers will evaluate the strength of the applicant's intellectual property (IP) portfolio/position (pertinent to the proposed project). Is the Intellectual Development Strategy described in detail including current patents, patent filings and future plans for IP filings, any known constraints that could impede the development of the compound (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed? 

Applications from Foreign Organizations

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.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAAA, 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. 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.
3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information
1. Award Notices

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

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the Protocol Registration and Results System Information Website ( NIH expects registration of all trials whether required under the law or not. For more information, see 

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.  Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at and in the application instructions (SF424 (R&R) and PHS 398).

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


Prior to funding an application, NIAAA Program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the NIAAA review panel or NIAAA Program staff.  A final set of milestones will be specified in the Notice of Award.

Progress towards achievement of the final set of milestones will be evaluated by NIAAA Program staff.  NIAAA Program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued.  In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NIAAA portfolio balance and program priorities, competitive landscape, and availability of funds.

NIAAA emphasizes the importance of the robustness and reproducibility of experimental results.  In some cases, conducting additional critical experiments will be important for NIAAA to have confidence in making a funding decision.  Therefore, NIAAA Program staff, in consultation with the PD/PI, may add experiments that need to be conducted prior to or during the award as an additional milestone(s). In some cases, these studies will be supported by additional funds from NIAAA.

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights 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 The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see; and Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at 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

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

Cooperative Agreement Terms and Conditions of Award

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

  • All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIAAA staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.
  • Meeting NIAAA policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study.
  • Upon implementation of the protocol, ensuring that each site, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, data collection, and quality control.
  • Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIAAA support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIAAA.
  • Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIAAA/NIH.
  • Obtaining prior written approval of the NIAAA Grants Management Specialist in consultation with the NIAAA Program Officer for any change in any of the key personnel identified in the Notice of Grant Award.

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:

The NIH Project Scientist will be extramural staff from NIAAA, who will have substantial involvement above and beyond the normal program stewardship of the award.  The NIH Project Scientist is a partner within the research team representing the government's interest in the substantive work of the research team with the following responsibilities:

  • Have substantial scientific/programmatic involvement during conduct of this cooperative agreement, through technical assistance, advice,
  • Coordinate with the awardees in monitoring issues relating to: design of the activities, recruitment, adherence to protocols, adjustment of study protocols, and management and technical performance.
  • Participate in all Steering Committee activities, including conference calls, subcommittees and special committees.
  • Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAAA staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
  • Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration.
  • Will not be involved in funding decisions and will not be allowed to attend review meetings of conflicted applications.

The NIH Program Official will be an NIAAA Staff who will be responsible for the normal scientific and programmatic stewardship of the award. Additional responsibilities include:

  • Participate in all Steering Committee meetings and conference calls.
  • Monitor recruitment status of the trial on an ongoing basis.
  • Monitor performance through consideration of quarterly meetings of the Steering Committee and annual reports, site visits, and compliance with NIH procedures.
  • Approve modifications to the research plan and/or study protocol(s) based on emerging data and/or other issues that impact progress of the project.
  • Determine if the awardee has met/achieved milestones throughout the project.
  • Determine if the awardee has met the milestones and feasibility requirements for transition of the project to the next year or stage of funding.
  • Reserve the right to obtain periodic external peer review, and recommend reviewers for, an assessment of progress and achievement of milestones.
  • Ensure timely registration of Phase I and Phase II trials in
  • Reserve the right to terminate or curtail the study (or an individual award) in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in milestone achievement (e.g., participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol), (c) substantive changes in the agreed-upon protocol with which NIAAA does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject ethical issues that may dictate a premature termination.
  • Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team.
  • Will be involved in funding decisions and attend review meetings of applications submitted in response to this FOA.

The NIAAA Staff will not have dual roles as Project Scientist and Program Officer.

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.

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free) Customer Support (Questions regarding registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

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

Scientific/Research Contact(s)

Raye Z. Litten, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0636

Peer Review Contact(s)

Ranga Srinivas, Ph.D.
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-2067

Financial/Grants Management Contact(s)

Jeffrey Thurston
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-9801

Section VIII. Other Information

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

Authority and Regulations

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

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