Required Application Instructions

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

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

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

The Funding Opportunity Announcement (FOA) invites applications to support research on various topics in the field of alcohol treatment and services for alcohol use disorders. The scope of interest is wide-ranging. It includes behavioral treatments; recovery strategies; and the organizational, financial, management, and environmental factors that facilitate or inhibit the delivery of evidence-based services for alcohol use disorders.

Research objectives of this FOA include, but are not limited to, research within the following three broad research domains: (1) behavioral therapies and mechanisms of behavioral change; (2) health services research; and (3) recovery research. Cutting across these domains, NIAAA encourages studies on a number of special emphasis populations and topics including: (a) treatment for PTSD and alcohol use disorders, (b) treatment for adolescents, (c) fetal alcohol spectrum disorders, (d) health disparities/special populations, and (e) use of novel methods and technologies.

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

NIAAA’s priorities in behavioral, health services, and recovery research are covered in this FOA and the companion R21 and R03 announcements. Medication development applications should now use PA-15-256 (R01), PA-15-255 (R03), or PA-15-254 (R21).

To ensure that applications are in-line with current program priorities, NIAAA strongly encourages all investigators to contact the Scientific/Research contact prior to developing an application.

1. Behavioral Therapies and Mechanisms of Behavioral Change

Over the past 20 years, research on the behavioral treatment of alcohol use disorders has progressed substantially. Behavioral interventions that have demonstrated efficacy include motivational enhancement therapy, cognitive behavioral therapy, brief interventions, behavioral couples therapy, twelve-step facilitation therapy, and the community reinforcement approach. Interestingly, several studies have suggested that these behavioral therapies appear to have similar efficacies when compared with standard treatments. Currently, very little information is available on how and why these behavioral treatments are effective. Understanding the underlying mechanisms of action of an intervention involves identifying the active processes and their specific effects on diverse patient groups, including racial/ethnic minority, rural, and low-income populations. Because many individuals with alcohol use disorders change their drinking behavior without help from addiction treatment providers or self-help groups, it is as vital to understand how and why people change their drinking outside of specialized treatment settings as it is within them.

Toward this goal of understanding the mechanisms of behavioral change, new transdisciplinary, multilevel, and collaborative approaches are needed that integrate multiple domains of knowledge , including cognitive, affective, and social neuroscience; neuroimaging; genomics; proteomics and metabolomics; social psychology; economics; and computational science. Progress in this complex and challenging area of treatment research will represent a major milestone for the alcohol treatment community.

Specific areas of research include, but are not limited to, the following examples:

Behavioral Therapies

• Identify and evaluate mechanisms underlying the effects of behavioral therapies.
• Develop innovative strategies to promote sustainable, positive drinking behavior change during both the initial phase of treatment and aftercare to maintain improvements in the long term.
• Develop strategies to enhance engagement, retention, and compliance of patients in treatment.
• Evaluate combinations and sequences of behavioral treatment.
• Evaluate the efficacy of specialized behavioral therapies in understudied populations, including the elderly; racial/ethnic minorities; individuals in the criminal justice system; U.S. military personnel, and veterans and their families; and patients suffering from co-occurring psychiatric disorders.
• Investigate mind body interventions (e.g., yoga, meditation, and biofeedback exercises) that may be used to reduce or prevent problematic drinking.

Mechanisms of Behavioral Change

• Conduct longitudinal studies of the natural history of behavioral change in drinking behavior. Transdisciplinary research including genetic, electrophysiological, and imaging techniques is encouraged. Innovative measures of real-time cognitive and affective change also should be developed.
• Reanalyze existing studies (secondary analyses) with new models looking at potential mechanisms of change prior to treatment, and within, outside, and after treatment.
• Conduct experiments to elucidate the causal relationship between proposed mechanisms of behavioral change and recovery outcomes.
• Investigate network theory and analysis and new methods of computational and mathematical modeling to understand the complex interactions among individuals, their social systems, and the treatment settings.
• Add supplemental questions, aims, and measures, such as assessments of behavioral change and social context, to existing alcohol treatment and epidemiological studies.

2. Health Services Research

Based on data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a national survey of the non-institutionalized population in the United States, it has become clear that the U.S. population is characterized by a continuum of drinking types, ranging from low-risk drinkers to high-risk and chronic, relapsing alcohol-dependent drinkers. Approximately 65 percent (144 million) of adult Americans drank alcohol at various times during the past year. Of those, 59 million Americans exceeded high-risk drinking limits and 18 million of these had a diagnosis of alcohol use disorders. Only an estimated 13 percent of people identified as alcohol dependent had ever received specialty alcohol treatment. Epidemiological data such as these demonstrate the need to broaden and enhance the continuum of health care for alcohol-related problems and disorders. The menu of alcohol services, and the organizations that deliver them, needs to be diversified, enhanced, extended, and provided in a range of settings that meet the needs of underserved groups needing interventions tailored to their specific alcohol-related issues. Treatments that are attractive, affordable, accessible, and effective for different types of drinkers need to be identified, tested, and adopted. For example, stepped care would be appropriate for reducing binge drinking in a college population, whereas collaborative care models that integrate treatments for addiction and co-occurring conditions in primary care would be more appropriate for alcohol-dependent individuals with co-occurring medical and/or psychiatric conditions.

These research challenges provide many exciting opportunities for advancing services research. Barriers to treatment must be identified and effective strategies developed to offset these barriers in a variety of settings, including specialty addiction settings, general medical settings (e.g., primary care and mental health care), and settings outside the medical sector (e.g., the workplace and criminal justice, social welfare, and school systems). At a minimum, services should include screening, brief intervention, and referral, if needed. New approaches to establishing more effective evidence-based practices include adaptive models personalized to subtypes of drinkers, long-term management of chronic alcohol dependence, concurrent management of multiple comorbidities, and the patient-centered medical home model. These and other innovative health care approaches need to be adapted and tested for application in real-world practice settings.

Treatment outcome research is needed that identifies, evaluates, and tests long-term outcome measures in clinical effectiveness trials. This research should focus on how best to measure outcomes

including drinking outcomes, quality of life, and alcohol-related consequences as well as measures of treatment quality and process from a multidisciplinary perspective. Applicants are also encouraged to discover and derive robust outcome measures from archival, policy, and other secondary data.

A recent review of the NIAAA health services research portfolio revealed a decade of significant advances in critical research areas while at the same time highlighting several important research gaps. As a result of the review and current trends in research on alcohol-related treatment, NIAAA encourages research from among the following five priority areas: implementation science, disease management, access to care, health disparities, and health economics.

Specific areas of research include, but are not limited to, the following examples:

Implementation Science

• Identify, develop, and test models and methods that can enhance the diffusion, implementation, and adoption of evidence-based alcohol-related treatment practices across the full spectrum of services for at-risk, harmful, and dependent drinkers.
• Identify, develop, and evaluate treatment outcomes for models tailored for non-medical settings (e.g., criminal justice, social welfare, workplace, and school settings) as well as models for medical non-specialty treatment settings (e.g., primary care and mental health services).

Disease Management

• Develop and evaluate cost-effective disease management approaches and algorithms suitable for chronic relapsing conditions.
• Develop and test approaches to individualized care for patients with complex comorbidities.
• Identify or develop and test interventions that enhance the adherence and retention of patients.

Access to Care

• Identify and develop strategies to reduce personal and organizational barriers that prevent people with alcohol use disorders from seeking and receiving appropriate care.

Health Disparities

• Expand research on factors contributing to health disparities to include a broad range of personal characteristics and community settings that may affect health outcomes.
• Assess and evaluate variations in health disparities across a range of treatment settings.
• Develop measures to assess the multiple components and dimensions of personal health disparities models (e.g., health literacy, access to health care, confidence in the proximal health system, socioeconomic status, sociocultural beliefs and practices related to alcohol use, and personal health care).

Health Economics

• Conduct natural history studies on the impact of changes in health care policy on alcohol-related services delivery and quality.

3. Recovery Research

The term recovery refers to the disappearance of the signs and symptoms of alcohol use disorder accompanied by a state of well-being following an episode of alcohol use disorder. Research indicates that there is a substantial level of recovery from alcohol dependence. Twenty years after the onset of alcohol dependence, about three-fourths of individuals are no longer dependent. Moreover, more than half of those individuals drink at low-risk levels without symptoms of alcohol dependence.

Approximately 75 percent of persons who recover from alcohol dependence do so without seeking any kind of help, including specialty alcohol programs and Alcoholics Anonymous (AA). Recovery outside of treatment is more likely in those with fewer symptoms of dependence and fewer comorbid psychiatric disorders. Notwithstanding the high rates of natural recovery from alcohol dependence, in most cases, it is a chronic relapsing illness with serious, often devastating psychological, medical, and social consequences for affected individuals and families over time. In many cases, whether or not affected individuals ever seek treatment, the adverse consequences of alcoholism extend well beyond the period of dependent drinking and may even span multiple generations.

What causes change in drinking behavior that leads to recovery? Because most individuals recover without treatment, it is important to study natural recovery by evaluating mediators and moderators of drinking behavior in subtypes of alcohol users. Biological, psychological, and contextual factors should be considered, including, but not limited to, cultural and socioeconomic milieu, lifestyle, endophenotypes, cognitive functioning, and sleep and other medical disorders.

Specific areas of research include, but are not limited to, the following examples:

• Conduct observational, epidemiological, or natural history studies that lay the foundation for understanding mediators and moderators of recovery in subtypes of alcohol users.
• Conduct systematic studies of natural recovery.
• Identify precipitants of relapse, including components of the protracted withdrawal syndrome, and evaluate the adverse effects of these precipitants on the course of recovery.
• Identify and evaluate mediators and moderators of recovery in different subtypes of alcohol users, including, but not limited to: variations associated with diverse cultural and socioeconomic milieus, developmental stage, lifestyle, endophenotypes, cognitive functioning, and sleep and other medical disorders.
• Understand the dynamics of both positive and negative changes in quality of life as a function of chronic drinking, recovery, and relapse.

A) Treatment for PTSD and Alcohol Use Disorders

Another high priority area for NIAAA is to develop effective behavioral treatments for individuals with co-occurring AUD and post-traumatic stress disorder (PTSD). Compared to non-comorbid individuals, those with this comorbidity tend to have a more severe clinical impairment, higher rate of psychosocial and medical problems, higher utilization of health services, higher suicide rate, and lower quality of life. PTSD can occur from a variety of traumatic experiences, and thus affect a variety of populations, subsequently increasing the risk of problematic drinking. Military personnel who have experienced combat are at particularly high-risk for developing PTSD and problematic drinking. An important clinical issue surrounding the treatment of this comorbidity is the heterogeneity underlying both AUD and PTSD.

A variety of behavioral interventions for co-occurring AUD and PTSD have been investigated or are currently under investigation. Among them: Prolonged Exposure Therapy (PE), Seeking Safety (SS) and Cognitive Processing Therapy (CPT).

Specific areas of research include, but are not limited to, the following examples:

• Tailor behavioral interventions to specific subpopulations of persons with co-occurring AUD and PTSD such as combat veterans, victims of sexual assault, or persons with traumatic brain injury (TBI).
• Application of new technologies such as web-based applications and virtual reality approaches to enhance the effectiveness and reach of behavioral interventions for co-occurring AUD and PTSD.

B) Treatment for Adolescents

Alcohol use remains a pervasive problem for adolescents in the United States, resulting in adverse and sometimes serious consequences. Approximately 12 percent of 12-year-olds, 30 percent of 14-year-olds, 60 percent of 16-year-olds, and over 70 percent of 18-year-olds consumed alcohol. Across all adolescents groups, there are approximately 7.2 million binge drinkers, 2.3 million heavy drinkers, and 1.5 million with alcohol use disorders. Most adolescents in treatment for alcohol and/or drug problems relapse after 6 months of conventional treatment. Researchers have begun to test a variety of behavioral therapies, including cognitive behavioral therapy, family-based interventions, multisystemic therapy, and motivational enhancement therapy.

Research on adolescent treatment is still in early stages. To design more effective treatments, it is important to develop a multidisciplinary approach that integrates biological, psychological, and social factors across different stages of development. Furthermore, future research needs to focus on subgroups of adolescents, including those with a range of alcohol severities, different comorbidities, racial ethnic groups, and cultural differences. Studies also should evaluate different settings, including rural, community, schools, unemployment programs, and the juvenile justice system.

Specific areas of research include, but are not limited to, the following examples:

• Develop and test behavioral treatments in adolescents with drinking problems. Interventions should be tailored to developmental, biological, psychological, and social needs of adolescents.
• Conduct longitudinal treatment studies of adolescents and develop advanced mathematical approaches that take into account diverse developmental processes and transitions.
• Explore different types of treatment endpoints for adolescents across the multiple stages of development.

C) Treatment for Fetal Alcohol Spectrum Disorders (FASD)

The FASD umbrella encompasses an array of health consequences of prenatal alcohol exposure including birth defects and neurological abnormalities in children whose mothers consumed alcohol during pregnancy. Fetal alcohol syndrome (FAS), a condition at the most severe end of the FASD spectrum, is characterized by facial dysmorphology, growth retardation, and brain damage, resulting in cognitive and behavioral impairments. Today, FAS remains the leading known preventable cause of mental retardation and other neurobehavioral disabilities. It is estimated that 1 to 2 per 1,000 live births in the United States have FAS, and the incidence of all FASD is on the order of 1 per 100 live births. A host of secondary impairments stem from the behavioral deficits of those with FASD. Their characteristic poor judgment, faulty social skills, and failure to learn from experience commonly lead to complications, such as substance use, arrest/incarceration, failure in school, economic problems, unemployment, and psychiatric comorbidities. Sadly, FASD is frequently not recognized or treated. A major research effort is needed to improve the identification and treatment of children and adults with FASD.

Specific areas of research include, but are not limited to, the following examples:

• Develop effective behavioral treatments for FASD-related problems, including, but not limited to, harmful drinking behaviors among children and adults with FASD.
• Investigate individual, familial, cultural, and/or environmental characteristics that mitigate or exacerbate the effects of prenatal alcohol exposure.
• Develop and/or validate markers to detect drinking and alcohol cessation interventions that are suited for pregnant women and safe for the developing fetus.

D) Treatment for Health Disparities/Special Populations

NIAAA seeks to elucidate the importance of alcohol treatment, service delivery, and recovery research among racial/ethnic groups and rural and low-income populations. In addition to these populations already experiencing health disparities in the United States, the recent immigration of large numbers of people from diverse cultures requires examination of existing treatment methods for relevance, efficacy, and effectiveness across all levels of adaptation/acculturation. Other subgroups with specific needs that often are understudied include: youths ages 18 to 25 not attending college; youths in the juvenile justice system and/or foster care; adults over the age of 65; youths and adults living in rural or other areas where treatment access is difficult; women residing in shelters for victims of domestic violence; the unemployed; minorities (e.g., Native Americans, African Americans, Hispanic Americans, and Asian American/Pacific Islanders); and adolescents and adults with developmental disabilities due to prenatal alcohol exposure. Of particular interest is comparative effectiveness research in special populations.

Military personnel, veterans, and their families are also an NIAAA priority. In particular, NIAAA seeks research on the development of effective alcohol screening instruments and treatments for this population. Behavioral treatment and services research should address a variety of comorbid conditions commonly found in this population, including posttraumatic stress disorder (PTSD), traumatic brain injury, depression, anxiety, sleep disturbances, and chronic pain. Of particular interest is research related to individuals who are serving or have served in Operation Enduring Freedom (Afghanistan) and Operation Iraqi Freedom (Iraq). In addition, research related to all phases of the deployment cycle (e.g., pre-deployment, deployment, reintegration, and separation) for all branches of the military and veterans is of interest. National Guard and Reserve service members, Individual Augmentees, and families have been identified as special needs populations that are of particular interest due to limitations in support related to not being attached to a military installation.

Specific areas of research include, but are not limited to, the following examples:

• Develop and implement effective behavioral treatments for understudied special needs populations.
• Identify and develop strategies to reduce personal and organizational barriers that prevent special populations with alcohol use disorders from seeking and receiving appropriate care.
• Investigate the application of evidence-based interventions with populations affected by health disparities and other special populations. Data-based elucidation of the conditions under which standard evidence-based interventions should be adapted with special populations is especially lacking in the literature.
• Explore the influence of culture, gender, race/ethnicity, socioeconomic status, and military service on seeking specialty treatment, remaining in treatment, and maintaining gains post-treatment.
• Investigate potential similarities and differences in mechanisms of behavioral change for problematic alcohol use among racial/ethnic minority, rural, and low-income populations; and military, veterans, and military family populations.

E) Use of Novel Methods and Technologies

Within the last decade, a number of novel methods and technologies have been developed to speed the course of alcohol treatment and related research. For instance, the widespread availability of the Internet, wireless technology, and computers has made possible a number of technological advances that capture important real-time information from patients in the field; synthesize, simulate, and statistically model large quantities of data in efficient and clinically meaningful ways; and deliver interactive computerized versions of promising behavioral interventions.

With the tremendous promise potentially afforded by these tools, research and development is continually evolving. More research is needed to further develop, refine, validate, and creatively implement these novel methods within alcohol clinical trials and treatment paradigms.

Specific areas of research include, but are not limited to, the following examples:

Technological Methods

• Develop and validate ecological momentary assessment (EMA) methods (e.g., interactive voice response technology, cell phones, and transdermal alcohol monitors) for capturing real-time data for use in clinical trials and treatment paradigms.
• Devise novel methods (e.g., Web-mining software of social networking sites) that capture social network information among groups at risk for alcohol dependence and high-risk drinking.
• Develop and validate efficacious computerized behavioral interventions for use in reaching remote or underserved populations of problem drinkers.

Statistical Methods

• Evaluate the impact of new statistical models and methods on treatment effectiveness outcomes for instance, comparing the relative impact of linear models and dynamic models on clinical trial outcomes.
• Develop and compare treatment outcome measures that are sensitive to the effects of treatment; evaluate the short and long-term clinical utility of these outcome measures.
• Use person-centered statistical approaches (e.g., trajectory analysis and growth mixture modeling) to capture changes in outcomes over time and convey results that are more clinically intuitive.
• Develop cross-design synthesis statistical methods to standardize and compare clinical data collected by different methods.
• Use in silico or other computation methods to facilitate development of new compounds for the treatment of alcohol dependence.
• Develop and implement new, efficient adaptive clinical trial designs and statistical analyses that allow for adjustments to treatment based on the changing disease status of the patient.
• Develop and compare statistical models and approaches to manage missing data in clinical trials.

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The letter of intent should be sent to:

Abraham P. Bautista, Ph.D.
Fax: 301-443-9737
Email: [email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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.

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

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

Part I. Overview Information contains information about Key Dates. 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.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

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

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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).

For this particular announcement, note the following: 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.

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 proposing 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 the trial needed to advance scientific understanding?

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 proposing 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 proposing 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?

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?

In addition, for applications proposing clinical trials: Does the application adequately address the following, if applicable:

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?

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?

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 proposing 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?

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.

Specific to applications proposing 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)?

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

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

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

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

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Not Applicable

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by 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.

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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

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

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

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

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

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials by law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nig.gov/ClinicalTrials_fdaaa/.

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 http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: [email protected]

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

Brett Hagman, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0638
Email: [email protected]

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

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-6328
Email: [email protected]

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

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