National Institutes of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
See Notices of Special Interest associated with this funding opportunity
This Notice of Funding Opportunity (NOFO) focuses on prevention and intervention strategies for fetal alcohol spectrum disorders (FASD) throughout the lifespan. The intent of this NOFO is to support research that advances (1) prevention approaches to reduce prenatal alcohol exposure and the incidence of FASD and (2) interventions for FASD. These objectives will be accomplished with the Exploratory/Developmental Phased Award (R61/R33) mechanism, clinical trial optional. The R61 phase will support pilot studies or secondary data analysis for hypothesis development and feasibility, and research testing the hypotheses can be expanded in the R33 phase. The transition to the R33 phase will be determined by NIAAA program staff after evaluation of the achievement of specific milestones set for the R61 phase. Highest priority will be given to applications with clinical trials. Applicants interested in planning clinical trials or adding to current projects may also consider NOFO (PAR-24-067, the R34 option).
30 days prior to the application due date
Application Due Dates | Review and Award Cycles | ||||
---|---|---|---|---|---|
New | Renewal / Resubmission / Revision (as allowed) | AIDS - New/Renewal/Resubmission/Revision, as allowed | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
February 16, 2024 | March 18, 2024 | Not Applicable | July 2024 | October 2024 | December 2024 |
June 17, 2024 | July 16, 2024 | Not Applicable | November 2024 | January 2025 | April 2025 |
October 16, 2024 | November 18, 2024 | Not Applicable | March 2025 | May 2025 | July 2025 |
February 17, 2025 | March 17, 2025 | Not Applicable | July 2025 | October 2025 | December 2025 |
June 16, 2025 | July 16, 2025 | Not Applicable | November 2025 | January 2026 | April 2026 |
October 16, 2025 | November 17, 2025 | Not Applicable | March 2026 | May 2026 | July 2026 |
February 16, 2026 | March 16, 2026 | Not Applicable | July 2026 | October 2026 | December 2026 |
June 16, 2026 | July 16, 2026 | Not Applicable | November 2026 | January 2027 | April 2027 |
October 16, 2026 | November 16, 2026 | Not Applicable | March 2027 | May 2027 | July 2027 |
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.
Not Applicable
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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
Prenatal alcohol exposure is a leading preventable cause of birth defects and neurodevelopmental deficits in the United States. Fetal alcohol spectrum disorders (FASD) can occur in individuals who were prenatally exposed to alcohol. Alcohol can disrupt prenatal development at any stage during pregnancy, including the earliest stages, often before a woman knows that she is pregnant. A 2018 study estimated that 1 to 5 percent children in the first grade in the US have FASD, the majority of whom were previously undiagnosed.
FASD is an umbrella term for a range of physical, cognitive, and behavioral abnormalities caused by prenatal alcohol exposure. FASD may include any disorder within the FASD spectrum, e.g. fetal alcohol syndrome (FAS), partial FAS (pFAS), alcohol-related neurodevelopmental disorder (ARND), alcohol-related birth defects (ARBD), and neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE).
As prenatal alcohol exposure leads to heterogeneous clinical and non-clinical symptoms, individuals with FASD tend to have their own unique combination of day-to-day challenges, which may include medical, behavioral, educational, and social problems. People with FASD may have difficulty in areas of neurocognition (including global intellectual impairment, executive function deficits, poor working memory, learning problems); self-regulation (impulse control problems, impaired mood or behavioral regulation, attention deficits, organization difficulties); and adaptive functioning (communication issues, problems with daily living, poor social skills, gross or fine motor delay). Individuals are affected differently, with some having minor impairments in a single domain, whereas others have multiple difficulties and a lifelong developmental disability.
Through this initiative, NIAAA is interested in developing evidence-based prevention strategies to reduce the incidence of FASD and interventions/treatments to lessen the deficits in individuals affected by prenatal alcohol exposure. Reports from prenatal clinics and postnatal studies suggest that as many as 20-30 percent of women drink at some time during pregnancy. Several risk factors have been identified that place offspring at higher risk for FASD, including the level of alcohol consumption before and during pregnancy, later initiation of prenatal care, family history of drinking, and other factors.
Over the past decade, NIAAA supported the development of various treatment approaches using dietary supplements, sensorimotor training, behavioral interventions, and parenting strategies to improve outcomes in individuals with FASD. Similarly, NIAAA has funded research into screening, brief interventions, and treatment approaches for high-risk and vulnerable populations, including pregnant women. Despite these investments, challenges remain, with a critical need to build the evidence base for interventions to improve outcomes in individuals with FASD and for prevention strategies, including primary, secondary, and tertiary approaches, to decrease alcohol use during pregnancy and the incidence of FASD.
This NOFO encourages studies that propose strategies for prevention of FASD or intervention for individuals affected by FASD throughout the lifespan, through an R61/R33 mechanism. The R61 phase is the first two (2) years of the award, while the R33 spans the following three (3) years. The R61 phase supports initial technical development and proof-of-principle projects, whereas the R33 phase supports further development, application, and evaluation of clinical utility to lay the foundation with which to pursue a larger efficacy trial or study. The application should provide clear aims and measurable objectives for each phase of the proposed research, with explicit discussion of how the results of the R61 phase will inform the R33 phase. Initiation of the second (R33) phase of support is contingent upon successful accomplishment of the objectives and milestones investigators set out in the first (R61) phase of their research.
This NOFO is intended to support biomedical, behavioral, social sciences research in prevention and/or intervention, including new, exploratory and developmental efforts. Applicants should explicate a clear conceptual link between relevant biomedical, psychological, behavioral, or social factors, and the prevention or intervention components being proposed (including a description of the mechanism of action by which these components are hypothesized to have an effect), and their relationship to the outcomes that are being targeted.
Research aims may include, but are not limited to, determination of dosing levels and duration; side effects and safety monitoring; demonstration that outcome measures have appropriate sensitivity to change in the target population; demonstration of feasibility (implementing the intervention and study procedures, evaluating attrition); and working out details of the experimental protocol (e.g., the assessment, experimental intervention and comparison intervention protocols; and randomization procedures, if appropriate).
Study topics include, but are not limited to, the following:
The R61 phase supports initial technical development and proof-of-principle projects, whereas the R33 phase supports further development, application, and evaluation of clinical utility to lay the foundation with which to pursue a larger efficacy trial or study. The application should provide clear aims and measurable objectives for each phase of the proposed research, with explicit discussion of how the results of the R61 phase will inform the R33 phase. Projects should include the following:
Identification of previous studies and data that will be used to generate or support hypotheses about prevention and/or intervention research in the R33 phase
Measurable outcomes for the R61 phase studies, i.e. an intervention protocol, pilot projects, feasibility data
Clear milestones for the R61 phase and related scientific goals for the R33 phase
Proposed pre-clinical studies during the R61 should translate to clinical human studies during the R33 phase
The objectives for the R33 phase should be based on the findings from the R61 phase. Examples of the goals for the R33 phase include, but are not limited to:
Identification of points of prevention or intervention for alcohol use or alcohol use disorder, based on the biological response and amount and timing of prenatal alcohol exposure
Studies of pharmacological targets or drug candidates for prevention of FASD or intervention to improve FASD-related outcomes
Identification of specific targets and intervention components based on psychosocial mechanisms Rigorous efficacy or effectiveness trials of prevention strategies and/or interventions that translate into clinical practice; studies that assess implementation and scalability of efficacious prevention strategies, policy, and/or interventions.
Transition to the R33 phase is contingent upon programmatic review that will include, but is not limited to, satisfactory demonstration that the R61 milestones have been achieved. Transition to the R33 phase is not guaranteed for all grants awarded under this NOFO.
The main goal of this opportunity is to support research on prevention and intervention strategies to reduce prenatal alcohol exposure and its effects. Applications relating to prenatal exposure to multiple substances (nicotine, cannabis, opioids, methamphetamine, and/or prescription drugs) will be considered as responsive; however, the focus is expected to be prenatal alcohol exposure. Animal experiments may be necessary for pre-clinical testing; however, the focus of this NOFO is the translation of findings.
Applications on the following topics will not be considered responsive to this NOFO and will not be reviewed.
It should be noted that although estimation of effect sizes is a logical step in evaluating the efficacy of a prevention or intervention strategy or treatment, studies conducted under this mechanism are likely to have small sample sizes, resulting in potentially unstable and unreliable effect size estimates that would have limited utility in power calculations for a larger clinical trial. Therefore, while encouraged, attempting to obtain an estimate of effect size is not an expected outcome.
Applicants are strongly encouraged to consult the Scientific/Research Contact listed below to discuss the alignment of their proposed work with the objectives of this NOFO.
See Section VIII. Other Information for award authorities and regulations.
Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.
Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Optional: Accepting applications that either propose or do not propose clinical trial(s).
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
For the R61 phase, the combined budget for direct costs during the two-year project period may not exceed $350,000 with no more than $225,000 requested in a single year. For the R33 phase, the direct costs must not exceed $500,000 per year.
The project period is limited to 2 years for the R61 phase and up to 3 years for the R33 phase. The total project period may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.
1. Eligible Applicants
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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.
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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information
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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
2. Cost Sharing
This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.
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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.
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:
The letter of intent should be sent to:
Dr. Philippe Marmillot
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-2861
Email: [email protected]
Page Limitations
All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Describe and clearly demarcate the specific aims for each of the two phases (R61and R33) on the single Specific Aims attachment. For the R61 phase, the specific aims should be focused on experiments that will test the proposed innovative concept/hypothesis. For the R33 Phase, the specific aims should outline generally the plan to explore the innovative concept/hypothesis if it is unambiguously supported by the experiments in the R61 phase.
Research Strategy:
The Research Strategy should contain separate sections that describe the R61 and R33 phases.
R61 Phase:
Applicants should include one or more critical experiments for rigorously testing the proposed concept/hypothesis. These experiments must be scientifically justified, specific, and feasible. Applicants should state explicitly the results that support, reject, or are inconclusive regarding testing of their concept/hypothesis, and are strongly encouraged to calculate and report effect size, in addition to statistical significance, whenever possible.
Preliminary Data:
An R61/R33 grant application need not have preliminary data, but they may be included if available.
Milestones:
Transition from the R61 to the R33 phase is contingent upon the successful completion of proposed milestones. These milestones are to be included as the last element of the Research Strategy section of the application and will be evaluated as part of the scientific and technical merit of the R61/R33 application. The milestones proposed in the application should be well-described, quantifiable, and scientifically justified to allow program staff to assess progress and successful completion of the R61 phase. Include a section labeled "Milestones" describing milestones to be achieved during the R61 phase to qualify for the transition to the R33 as part of Research Strategy within the approach section.
R33 Phase:
Although the Research Strategy for the R33 Phase is expected to be broad and somewhat speculative due to the unpredictable nature of the explorative research in the R61 Phase, the research strategy for the R33 phase of the award should be described based on anticipated results.
It is understood that the proposed milestones for the R33 phase may be revised based on activities during the R61 planning phase. In the event of an award, the PD/PI and NIH staff will negotiate a list of milestones for each year of support.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
As described in NOT-AA-23-001, NIAAA expects specific information in the Data Management and Sharing Plan (DMS Plan) to be included in NIAAA grant applications for due dates on or after January 25, 2023. In addition to the general NIH guidance regarding the information to include in the DMS Plan (NOT-OD-21-014, Supplemental Information to the NIH Policy for Data Management and Sharing: Elements of an NIH Data Management and Sharing Plan, and the NIH Data Management and Sharing Plan format page), NIAAA expects that the DMS Plan elements contain the following specific information:
Elements of the Data Management and Sharing Plan
Data Type:
This section should include details about the research subject, including species, sex, and cohort size. If specimens are collected from specimen sources, the type of specimen is to be listed, i.e., blood, tissue, urine, and whether the sample was collected in a prospective or retrospective time period
The data type specifies the nature of data: omics, medical and non-medical imaging, biological types (biochemical assays and biophysical such as X-ray and NMR, preclinical assays, electrophysiology), and phenotypic. Additional data to be included, i.e., associated metadata, epidemiology and surveillance, social/behavioral, clinical trials results, survey/questionnaire, and algorithms or simulations.
Standards:
For human subject data, a measure(s) of alcohol quantity and frequency is expected to be reported. Measures may include lifetime use, 30-day quantity and frequency, and/or maximum drinks per 24 hours. Demographic data should include sex, age, race, and ethnicity. Applicants are encouraged to consult the PhenX (https://www.phenxtoolkit.org/index.php) website and the Alcohol, Tobacco and Other Substances and the Demographics domains for protocols.
Studies that include animal models should include the alcohol exposure paradigm, age of the animal at the start and end of the alcohol exposure, a measure of alcohol consumption or exposure. A blood alcohol concentration measurement is recommended.
Data Preservation, Access, and Associated Timelines:
For additional information on submitting scientific data from studies with human subjects, see "Notice of NIAAA Data-Sharing Information for Human Subjects Grants Research Funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) [5th Revision]" (NOT-AA-23-002). For data types without human subjects, applicants will provide the name(s) of the repositories where the scientific data and metadata will be archived.
Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Organizations
Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
4. Submission Dates and Times
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to 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, NIHs electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.
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 How to Apply – Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
6. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.
7. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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 NOFO for information on registration requirements.
The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy
1. Criteria
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
This NOFO supports exploratory and developmental research on strategies on prevention of FASD and intervention for individuals with FASD. An R61/R33 grant application need not have preliminary data, but they may be included if available. Accordingly, reviewers will emphasize the following:
Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 Phases.
In addition, for applications involving clinical trials:
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
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 provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
In addition, for applications involving clinical trials
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this NOFO:
Can these experiments unambiguously test the hypothesis at hand, and are they feasible? Are the proposed milestones of the critical experiments well-defined with quantifiable measures that are appropriate for assessing the success of the R61 Phase of the award? Are the proposed critical experiments sufficient to determine if the project succeeded in accomplishing its specific aims? Is it clear how the R33 Phase of the study will develop and expand once the R61 Phase is completed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
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 involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the 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 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 individuals of all ages (including children and older adults) 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 will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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.
For Renewals, the committee will consider the progress made in the last funding period.
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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.
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.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAAA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
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:
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient 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, Recipients, and Activities, including of note, but not limited to:
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the HHS Office for Civil Rights website.
HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigators scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicants integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
3. Data Management and Sharing
Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
4. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Preclinical Studies and Medical Care
William Dunty, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-7351
Email: [email protected]
Elizabeth Powell, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0786
Email: [email protected]
Prevention and Epidemiology
Tatiana Balachova, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301.443.5726
Email: [email protected]
Behavioral, Pharmacological and Education Therapy
Deidra Roach, MD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301.443.5820
Email: [email protected]
Ranga Srinivas, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-2067
Email: [email protected]
Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.