The National Institute on Alcohol Abuse and Alcoholism solicits applications for an R01 Clinical Trial Required mechanism focusing on alcohol treatment and recovery research. This NOFO will focus broadly on topics relevant for treatment of and recovery from alcohol use disorder (AUD), including: medications development, precision medicine, behavioral therapies and mechanisms of behavioral change (MOBC), recovery, translational research, and innovative methods and technologies for AUD treatment and recovery.

PA-25-163: Alcohol Treatment, Pharmacotherapy, and Recovery Research (R01 Clinical Trial Required)

Posted Date: November 27, 2024 Expiration Date: September 08, 2026

Important Updates:

• March 31, 2025: This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.
• April 4, 2024: Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
• August 31, 2022: Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
• August 5, 2022: Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.

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: Alcohol Treatment, Pharmacotherapy, and Recovery Research (R01 Clinical Trial Required) Activity Code: R01 Research Project Grant Announcement Type: Reissue of PAR-23-250

Related Notices:

• See Notices of Special Interest associated with this funding opportunity.

Funding Opportunity Number (FON): PA-25-163 Companion Funding Opportunity: PA-25-245 (R01 Research Project), PAR-25-192 (R34 Planning Grant), PAR-25-193 (R34 Planning Grant)

Number of Applications: See Section III. 3. Additional Information on Eligibility

Assistance Listing Number(s): 93.273

Funding Opportunity Purpose: The National Institute on Alcohol Abuse and Alcoholism solicits applications for an R01 Clinical Trial Required mechanism focusing on alcohol treatment and recovery research. This NOFO will focus broadly on topics relevant for treatment of and recovery from alcohol use disorder (AUD), including: medications development, precision medicine, behavioral therapies and mechanisms of behavioral change (MOBC), recovery, translational research, and innovative methods and technologies for AUD treatment and recovery.

Key Dates:

• Posted Date: November 27, 2024
• Open Date (Earliest Submission Date): January 05, 2025

Standard Due Dates (marked with an asterisk):

• All applications are due by 5:00 PM local time of applicant organization.
• Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions:

• It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).
• Conformance to all requirements (both in the Application Guide and the NOFO) 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.
• Submission must be through Grants.gov using one of the following options:
  • NIH ASSIST system
  • Institutional system-to-system (S2S) solution
  • Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this PAR is to advance research on various topics that fall within NIAAA’s Division of Treatment and Recovery (DTR). DTR’s research interests are wide-ranging but typically encompass broad categories such as medications development; behavioral therapies, including mechanisms of behavioral change (MOBC); recovery; translational research; and innovative methods and technologies for alcohol use disorder (AUD) treatment. Other areas of interest include topics focusing on special-emphasis and underserved populations. Specific examples include research related to health disparities, age, sex, race and ethnicity, co-occurring disorders, and military populations.

Background

AUD is a global health problem, affecting more than 76 million adults worldwide, including over 14.5 million 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. Research is needed to develop effective treatments for AUD and to better understand the complex nature of recovery across a broad range of topic areas and populations, as described in detail below.

Research Objectives

Medications Development

• All studies must be conducted in humans.
• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Evaluate the efficacy and safety of experimental medications (either repurposed or novel compounds) that bind to new targets to treat AUD.
  • Assess the efficacy and safety of medications to treat comorbid AUD and psychiatric (e.g., posttraumatic stress disorder [PTSD]) disorders.
  • Determine who responds favorably during the trial by exploring clinical and behavioral characteristics and biological markers.
  • Explore new human laboratory paradigms that will help predict efficacy in clinical trials of experimental medications.
  • Leverage relationships with pharmaceutical and biotechnology companies to identify new compounds for testing in clinical trials.

Behavioral Therapies

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that evaluate evidence-based behavioral therapies in real-world treatment settings, especially for culturally varied, special emphasis, and underserved populations.
• Use dynamic and person-centered statistical modeling approaches to evaluate how heterogeneity impacts alcohol use behavior within specific AUD treatments.
• Conduct micro-intervention studies to isolate and test the importance of key treatment-related mediators and moderators.
• Develop new and adapt existing interventions for AUD based on emerging findings from research on MOBC.
• Translate evidence-based MOBC best practices into clinical practice.
• Engage in complex research designs (e.g., dismantling studies), which enhance support and provide evidence for the mechanisms underlying established AUD behavioral treatments.

Recovery from AUD

• NIAAA developed an operational definition of “recovery” from AUD. The definition involves remission from AUD and cessation from heavy drinking. Moreover, recovery is associated with improvements in dimensions of well-being, quality of life, and biopsychosocial functioning.
• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Explore the neurobiological, psychological, environmental, social, and spiritual factors that influence post-treatment recovery.
  • Identify novel mechanisms of behavioral change (MOBC) that help maintain behavior change in recovery (e.g., self-regulation), and evaluate how knowledge about these mechanisms can be applied to recovery.
  • Determine the trajectories of recovery in subgroups of people with different socioeconomic backgrounds, cognitive abilities, and medical histories, including examining sex-related differences in trajectories of recovery within these groups.
  • Characterize the relationships among relapse severity, frequency, and timing in the recovery process, including how relapse impacts the potential for long-term recovery and improvement in biopsychosocial functioning.
  • Understand the role of understudied mutual support groups, as well as spirituality and religion, in treatment and recovery from AUD.
  • Identify the factors associated with so-called spontaneous or “natural” recovery and how these factors can be applied to change the behavior of those in treatment.
  • Explore continuing care treatments and interventions that aim to support long-term recovery.
  • Define and measure dimensions of functioning and well-being associated with recovery (e.g., which of these dimensions of functioning and well-being are positively vs. negatively associated with recovery? Which of these dimensions of functioning and well-being are the most integral in recovery? To what degree might these functioning measures be feasible in clinical practice?).

Translational Research

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Translate key neuroscience research findings (e.g., neurobiological, cognitive, emotion regulation, and genetic) to develop more effective treatments.

Innovative Methods and Technologies for AUD Treatment and Recovery

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Apply new technology (e.g., mobile devices, computer, web-based applications) to evidence-based behavioral treatments to improve the effectiveness of telemedicine and to reach remote and underserved, vulnerable populations.
  • Investigate new ways of capturing real-time data in clinical trials and treatment protocols (e.g., interactive voice response technology, smartphones, and alcohol sensors).
  • Explore new analytical methods for evaluating treatment and recovery.

Special-Emphasis Populations

Health Disparities

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Develop and implement effective treatments tailored to populations affected by health disparities in a variety of clinical and nontraditional settings.
  • Determine how social/cultural factors influence treatment accessibility, effectiveness, and long-term recovery.
  • Develop measures to assess care delivery models to better understand the issues underlying disparities (e.g., health literacy, access to health care, confidence in the proximal health system, socioeconomic status, sociocultural beliefs and practices related to alcohol use, multi-morbidity with other health issues, and personal health care).

AUD Patients with Psychiatric Comorbidity

• Examples of high-priority research areas appropriate for evaluation include, but are not limited to, investigations that:
  • Integrate treatment for co-occurring AUD and mental health conditions to address the heterogeneity that exists among patients. Explore how behavioral interventions and medications can be combined to treat AUD patients with co-occurring PTSD; anxiety; depression; insomnia; and other mental health conditions, including timing of interventions (serial vs. concurrent), separate vs. fully integrated treatment, and dose/frequency of treatment components.
  • Identify which types of services, service providers, and treatment settings work best for specific subgroups receiving treatment.
  • Determine how the treatment of one disorder can influence the risks and outcomes for other disorders.

Women

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Develop new strategies for alcohol screening, diagnosis, and interventions; and tailor these approaches to women in a variety of settings, including prenatal care and specialty health care.
  • Examine the effects of stress, early childhood trauma, and co-occurring disorders on women’s drinking.
  • Determine the effectiveness of standard treatment approaches, such as group counseling and relapse prevention, in single-sex vs. mixed-sex groups.
  • Develop innovative strategies to improve coordination of care for women and their families across primary care, maternal health services, specialty alcohol treatment services, and other integrated health system components.

Adolescents and Young Adults

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Develop and test integrated behavioral treatments in adolescents and young adults with AUD that are tailored to the developmental, biological, psychological, emotional, and social needs of these ages.
  • Test novel approaches (e.g., sequential, multiple assignment, randomized trials–[SMART] trials) to adapt interventions at the individual level and/or to account for comorbidity and cultural factors or other considerations specific to the target groups.

Older Adults

• Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that:
  • Develop screening and behavioral and pharmaceutical therapies targeted to older adults.
  • Identify vulnerabilities in high-risk subgroups of older adults, including those with physical and/or mental health comorbidities; women; and people with cultural, socioeconomic, immigrant, and sex status.

Applications that focus on the following topics will NOT be considered responsive to this NOFO and will NOT be reviewed:

• Efficacy and dissemination studies of brief interventions for high risk and understudied populations (e.g., individuals who are not 4-year college students or graduates, individuals experiencing poverty or comorbidity).
• Approaches that focus on enhancing positive health or other behaviors that might have an indirect positive effects on drinking, sleep improvement, and fitness.
• Role of life events and social factors as contributors to changes in the patterns of drinking. This includes understanding how the positive social effects of drinking influence the initiation and escalation of drinking, and how social forces and life events facilitate change are needed.
• Link changes in environmental factors such as the relative availability and price of alcohol and alcohol-free rewards associated with changes in drinking, and how to leverage these factors in treatment.
• Preclinical animal studies, only human studies are allowed in this PAR.
• HIV-AIDS related Studies.
• Studies that include substances other than alcohol or on poly-substance use disorders.
• Clinical trials on prevention.
• Clinical trials in community settings (community centers, college campuses etc.).
• Clinical Trials that include organ-associated diseases.
• Basic experimental studies involving humans (BESH).

Section II. Award Information

Funding Instrument: Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed:

• New
• Resubmission

Clinical Trial? Required: Only accepting applications that propose clinical trial(s).

Funds Available and Anticipated Number of Awards: The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget:

• Direct costs may not exceed $500,000 without prior approval (see Section IV. Application and Submission Information).

Award Project Period:

• The maximum project period is five years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations:

• Higher Education Institutions (Public/State Controlled, Private)
• Nonprofits Other Than Institutions of Higher Education (Nonprofits with 501(c)(3) IRS Status, Nonprofits without 501(c)(3) IRS Status)
• For-Profit Organizations (Small Businesses, Other than Small Businesses)
• Local Governments (State, County, City or Township, Special District)
• Indian/Native American Tribal Governments (Federally Recognized, Other than Federally Recognized)
• Federal Governments (Eligible Agencies of the Federal Government)
• U.S. Territory or Possession
• Other (Independent School Districts, Public Housing Authorities/Indian Housing Authorities, Native American Tribal Organizations (other than Federally recognized tribal governments), Faith-based or Community-based Organizations, Regional Organizations)
• Non-domestic (non-U.S.) Entities (Foreign Organizations) 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:

• System for Award Management (SAM): Must be active and renewed at least annually.

• NATO Commercial and Government Entity (NCAGE) Code: Required for foreign organizations (in lieu of CAGE code).

• Unique Entity Identifier (UEI): Issued as part of the SAM.gov registration process.

• eRA Commons: Must be in place by time of submission. Requires at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account.

• Grants.gov: Must have an active SAM registration to complete.

• Note: Registration can take 6 weeks or more. Begin the process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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 create a new account or affiliate their existing account with the applicant organization.
• If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts.
• 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.

2. Cost Sharing

• This NOFO does not require cost sharing.

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.

Section IV. Application and Submission Information

1. Requesting an Application Package

• The application forms package must be accessed through ASSIST, Grants.gov Workspace, or an institutional system-to-system solution.

2. Content and Form of Application Submission

• Follow instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed otherwise in this NOFO.
• Page Limitations: Follow all page limitations described in the How to Apply- Application Guide and the Table of Page Limits.

Instructions for Application Submission:

• SF424(R&R) Cover: Follow Application Guide instructions.
• SF424(R&R) Project/Performance Site Locations: Follow Application Guide instructions.
• SF424(R&R) Other Project Information: Follow Application Guide instructions.
• SF424(R&R) Senior/Key Person Profile: Follow Application Guide instructions.
• R&R or Modular Budget: Follow Application Guide instructions.
• R&R Subaward Budget: Follow Application Guide instructions.
• PHS 398 Cover Page Supplement: Follow Application Guide instructions.
• PHS 398 Research Plan:
  • Resource Sharing Plan: Comply with Application Guide instructions.
  • Other Plan(s):
    • Data Management and Sharing Plan: All applications must address a Data Management and Sharing Plan, regardless of the amount of direct costs requested.
  • Appendix: Only limited Appendix materials are allowed. No publications or other material, except blank questionnaires or surveys, may be included.
• PHS Human Subjects and Clinical Trials Information:
  • If "Yes" to "Are Human Subjects Involved?", include at least one human subjects study record.
  • Study Record: PHS Human Subjects and Clinical Trials Information: Follow Application Guide instructions.
  • Delayed Onset Study: Follow Application Guide instructions.
• PHS Assignment Request Form: Follow Application Guide instructions.

Foreign Organizations:

• Follow policies described in the NIH Grants Policy Statement and procedures for foreign organizations in the How to Apply- Application Guide.

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

• See Part 2. Section III.1 for information regarding UEI and SAM registration requirements.

4. Submission Dates and Times

• Application Due Dates: See Key Dates in Part 1.
• Applications must be submitted to Grants.gov.
• Track application status in eRA Commons.
• Errors must be corrected and a changed/corrected application submitted to Grants.gov on or before the application due date and time.
• Applicants are responsible for viewing their application before the due date in eRA Commons to ensure accurate and successful submission.

5. Intergovernmental Review (E.O. 12372)

• Not Applicable.

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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

• Applications must be submitted electronically. Paper applications will not be accepted.
• Complete all required registrations before the application due date (See Section III. Eligibility Information).
• eRA Commons ID: All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form.
• The unique entity identifier provided on the application must match the organization’s profile in eRA Commons and for SAM.
• Notification of Submission: Applicants are requested to notify the NIAAA Referral Office by email at [email protected] when the application has been submitted. Include NOFO number and title, PD/PI name, and title of the application.
• Requests of $500,000 or more for direct costs in any year:
  • Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/Research Contact at least 6 weeks before submitting the application.
• Mandatory Disclosure: Recipients or subrecipients must submit information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. Send written disclosures to the NIH Chief Grants Management Officer and the HHS Office of Inspector General.
• Post Submission Materials: Follow instructions in the policy and any additional instructions in this NOFO.

Section V. Application Review Information

1. Criteria

Applications are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact: Reviewers will provide an overall impact score reflecting the likelihood of the project to exert a sustained, powerful influence on the research field(s).

Scored Review Criteria:

• Factor 1. Importance of the Research (Significance and Innovation):
  • Significance: Importance of the research, gap in knowledge addressed, critical problem solved, conceptual or technical advance. Rationale and rigor of scientific background.
  • Innovation: Extent to which innovation influences the importance of the research. Novel concepts, methods, or technologies, or novel uses of existing ones.
• Factor 2. Rigor and Feasibility (Approach):
  • Rigor: Potential to produce unbiased, reproducible, robust data. Rigor of experimental design, appropriate controls, sufficient sample size, quality of analysis/interpretation plans. Plans to address relevant biological variables (sex, age). For human subjects/animals: rigor of intervention, justified outcome variables, generalizability/relevance, appropriate/diverse sample.
  • Feasibility: Soundness and achievability of the proposed approach, plans to address problems. For human subjects/clinical trials: adequacy/feasibility of recruitment/retention plan, likelihood of achieving enrollment, feasibility of study timeline/milestones.
• Factor 3. Expertise and Resources (Investigator(s) and Environment):
  • Investigator(s): Demonstrated background, training, and expertise. Quality of leadership plan for MPI applications.
  • Environment: Appropriateness of institutional resources.

Additional Review Criteria (Considered but not scored):

• Protections for Human Subjects
• Vertebrate Animals
• Biohazards
• Resubmissions
• Renewals
• Revisions

Additional Review Considerations (Not scored, not for overall impact):

• Authentication of Key Biological and/or Chemical Resources
• Budget and Period of Support

2. Review and Selection Process

• Applications will be evaluated by appropriate Scientific Review Group(s) convened by NIAAA.
• Applications may undergo a selection process where only the highest-scoring applications are discussed.
• Applications will compete for available funds.
• A second level of review will be by the appropriate national Advisory Council or Board.
• Funding decisions will consider:
  • Scientific and technical merit.
  • Availability of funds.
  • Relevance to program priorities.
• Just-in-Time Information: NIH may request "just-in-time" information before making an award.
• Federal Award History: NIH reviews applicant's federal award history in SAM.gov.

3. Anticipated Announcement and Award Dates

• Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
• Summary Statements (written critiques) will be accessible via the eRA Commons.

Section VI. Award Administration Information

1. Award Notices

• A Notice of Award (NoA) is the official authorizing document.
• Recipients agree to comply with all provisions in effect during the award period.
• ClinicalTrials.gov: If an award involves clinical trials, the responsible party must register and submit results information.
• Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure all protocols are reviewed by their IRB or IEC.
• Data and Safety Monitoring Requirements: Applies to all NIH-conducted or -supported human intervention studies.
• Investigational New Drug or Investigational Device Exemption Requirements: Clinical research projects involving investigational therapeutics must be performed under an FDA IND or IDE.

2. Administrative and National Policy Requirements

• 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• NIH Grants Policy Statement is part of the terms and conditions in the Notice of Award.
• Recipients must follow all applicable nondiscrimination laws and submit an Assurance of Compliance (HHS-690).
• All federal statutes and regulations relevant to federal financial assistance.
• Recipients are responsible for ensuring compliance with all applicable federal regulations. NIH may terminate awards for noncompliance.

Cooperative Agreement Terms and Conditions of Award: Not Applicable.

3. Data Management and Sharing

• Consistent with the 2023 NIH Policy for Data Management and Sharing, recipients must adhere to the requirements outlined in the NIH Grants Policy Statement.

4. Reporting

• Research Performance Progress Report (RPPR): Submitted annually.
• Financial Statements: Submitted as required in the NIH Grants Policy Statement.
• A final RPPR, invention statement, and expenditure data are required for closeout.

Section VII. Agency Contacts

Inquiries: Inquiries concerning this funding opportunity are encouraged.

Application Submission Contacts:

• eRA Service Desk:
  • Online: https://www.era.nih.gov/need-help (preferred)
  • Phone: 301-402-7469 or 866-504-9552
• General Grants Information:
  • Email: [email protected] (preferred)
  • Phone: 301-480-7075
• Grants.gov Customer Support:
  • Phone: 800-518-4726
  • Email: [email protected]

Scientific/Research Contact(s):

• Clinical, Treatment and Recovery Research:
  • Brett T. Hagman, Ph.D.
  • NIAAA
  • Phone: 301-443-0638
  • Email: [email protected]
• Medications Development:
  • Dan Falk, Ph.D.
  • NIAAA
  • Phone: 301-443-0788
  • Email: [email protected]

Peer Review Contact(s):

• RV Srinivas, Ph.D.
• NIAAA
• Phone: 301-451-2067
• Email: [email protected]

Financial/Grants Management Contact(s):

• Judy Fox
• NIAAA
• Phone: 301-443-4707
• Email: [email protected]

Section VIII. Other Information

• 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 2 CFR Part 200.
• All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.