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

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

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

This announcement provides support for (a) analyzing previously collected data in order to address key issues that have emerged from recent findings in alcohol epidemiology and prevention research, Genome Wide Association Studies (GWAS) or (b) developing new analytic techniques for conducting studies in alcohol epidemiology, prevention and Genetic/Genomic research.

Background

Epidemiologic and Genetic research projects typically generate data with potential utility beyond the specific hypotheses and questions that they were designed to address. In addition, the general progress of the field often uncovers new questions which could be, in part or in whole, addressed through the application of data originally gathered from previous projects and for other purposes. Furthermore, given the expense of original data collection and the constrained national budget for research support, making use of existing data to answer new and emerging questions is a sensible use of scientific resources. Sections of the announcement below highlight areas where emerging scientific questions in the alcohol field seem especially amenable to fruitful analyses using existing data. At the same time, the development of new analytic techniques, statistical and genetics methods for alcohol research typically employs existing data sets to refine these methodological advances. This announcement also encourages the development of such techniques, approaches, models, and measurement systems through research that employs data that are already available. Below are highlighted some technical developments of interest to the field that could be advanced using existing data.

Applicants interested in either approach should consider the wide range of existing data sources, such as population surveys, clinical trials and non-survey data collected by local, state or federal government agencies that are available in the alcohol field. These include the National Longitudinal Alcohol Epidemiologic Survey (NLAES); the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) conducted by NIAAA; the National Longitudinal Survey of Youth (NLSY) conducted by the U.S. Department of Labor; the National Adolescent Student Health Survey (NASHS), a cooperative project of the U.S. Department of Health and Human Services, Public Health Service, Office of Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, and the National Institute on Drug Abuse; the National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics (NCHS); the National Health Interview Survey (NHIS) conducted by NCHS; the National Survey on Drug Use and Health (NSDUH) (formerly the National Household Survey on Drug Abuse (NHSDA) and National Survey of Substance Abuse Treatment Services (N-SSATS), conducted by the Substance Abuse and Mental Health Services Administration; and the National Mortality Follow-back Survey conducted by NCHS. Non-survey data resources include Fatality Analysis Reporting System (FARS), a nationwide census collected by National Highway Traffic Safety Administration(NHTSA) that provides public yearly data regarding fatal injuries suffered in motor vehicle traffic crashes; The Uniform Crime Reporting (UCR) Program, collected by FBI; National Emergency Medical Services Information System (NEMSIS), a cooperative project of NHTSA and the Health Resources and Services Administration (HRSA) that is designed to provide a uniform national emergency medical services dataset, with standard terms, definitions, and values, as well as a national EMS database, with aggregated data from all states on a limited number of data elements. Data Base of Genotypes and Phenotypes at NCBI (www.dbgap.ncbi.nlm.nih.gov) that includes GWAS data sets for hundreds of diseases and disorders. These data are from case-control and family studies whose members were genotyped with half to more than two million SNPs (single nucleotide polymorphisms).

Applicants may also secure access to other data sets that may or may not be in the public domain, such as those collected under research grant funds, sponsored by private entities (e.g., philanthropic foundations, motor vehicle administrations, or commercial businesses) or originally collected for purposes other than research (e.g., health care, criminal justice or insurance data). One way of exploring available public data offerings is to consult the Alcohol Epidemiology Data Directory. This directory is compiled by NIAAA's Alcohol Epidemiologic Data System and is a compendium of existing public data resources available in the alcohol epidemiology field. It is available on NIAAA's website at: http://pubs.niaaa.nih.gov/publications/datasys.htm or from an NIAAA contractor: CSR, Incorporated, 2107 Wilson Boulevard, Suite 1000, Arlington, VA 22201, 703-312-5220(Tel), 703-312-5230 (Fax), [email protected].

Research Areas of Interest

Methodology Development

Single or multiple data sets may be used to develop new or improved research designs, measurement techniques, or analytic approaches. For example, researchers may wish to develop new analytic techniques for longitudinal designs that take into account transitions in alcohol and other drug use behaviors over time, or use existing data to undertake the simulation of complex systems for predicting the use of alcohol or the emergence of alcohol-related problems at an individual, group, or community level. Appropriate approaches for this announcement include methodologies that help develop accurate measurement of alcohol exposure, risk relationship and outcomes of alcohol consumption, or advance understanding of the causes, development, consequences of alcohol use and therefore provide information for forming efficient treatment as well as prevention approaches.

Examples of methodology research that are encouraged include:

• Spatial statistical methodologies that advance knowledge on alcohol and related outcomes in geographic context
• Statistical methodologies for alcohol longitudinal studies of life-cycle effects and processes
• Statistical and computational modeling approaches that identify, describe and predict individual-level alcohol consumption patterns, processes and related risk factors across various timeframes
• Systems science methodologies (i.e., systems-based simulation modeling methods), such as agent-based, network, system dynamics, and microsimulation modeling, that examine the simultaneous effects of alcohol related behaviors or interventions on multiple outcomes of interest as well as the mechanisms underlying such relationships
• Analytical approaches for real-time assessment of alcohol consumption and related behaviors, such as through the use of ecological momentary assessment (EMA), mobile, or sensor technologies
• Develop, improve and validate effective measurement of alcohol consumption and related risk behaviors that is developmentally appropriate. Such measurement will enable us to better understand risky alcohol involvement and help establish effective intervention program across life span
• Develop new tools for pathway and gene network analysis or improve/modify the existing tools that would fit better for alcohol related phenotypes

Fetal Alcohol Spectrum Disorders

Prenatal alcohol exposure is the leading preventable cause of birth defects in the U.S. Fetal alcohol spectrum disorders (FASD) can occur following prenatal alcohol exposure resulting in a distinctive set of anthropometric and central nervous system abnormalities across a continuum of severity, ranging from mild to moderate cognitive and growth deficiencies to severe mental retardation. NIAAA-supported active case ascertainment studies across multiple U.S. communities have estimated the prevalence of fetal alcohol syndrome (FAS) to be at least two cases per 1,000 and of FASD to be nearly 20 cases per 1,000, with much higher rates reported in some high-risk communities in South Africa, Russia and Italy. Cumulative costs of care for all FAS-affected individuals in the U.S. have been estimated at up to $6 billion annually. Variable rates in high-risk populations across global regions reflect varied cultural norms in drinking.

Reports from prenatal clinics and postnatal studies suggest that 20 to 30 percent of women drink at some time during pregnancy. Several maternal risk factors have been identified to place offspring at risk for FASD, including moderate to heavy maternal alcohol consumption prior to, during and after pregnancy, poor prenatal care and nutrition, family history of heavy drinking, multiple pregnancies, and social disadvantage. Though much has been published on refining diagnostic criteria for FASD in specific high-risk, heavily drinking populations, more research on the full range of drinking patterns resulting in prenatal alcohol exposure across gestational periods, as well as the etiology of neurodevelopmental effects across the lifespan of prenatally affected individuals is desired. Whereas most cases of FAS have been diagnosed in children of heavily drinking mothers, the precise quantity and frequency of alcohol consumption and timing of gestational exposure required to produce abnormalities is unknown. Increased understanding of dynamic patterns of alcohol exposure and resultant FASD outcomes can help inform health services interventions for prevention and treatment. NIAAA encourages secondary analysis of FASD data from clinic-based assessments, archival and electronic health records, epidemiologic and observational studies, and prevention and treatment studies, including but not limited to attention on the following:

• Effects of timing of exposure in humans (cumulative versus peak dosage) as well as periods of gestational exposure on a range of offspring chronic disorders and disabilities from infancy to adulthood
• Prospective associations between maternal drinking patterns and conduct disorder or other externalizing problems among prenatally exposed offspring from adolescence through young adulthood
• Influence of exposures to co-occurring prenatal alcohol and other substance use or life stressors
• Examination of a range of severity of alcohol exposure data combined across clinical studies to establish reliable and plausible thresholds to distinguish the utility of research-based diagnostic criteria from rapid screening criteria used in routine clinical practice
• Rates of adoption by primary or OB-GYN providers of screening, brief intervention or other alcohol use assessments or message delivery practices to women of childbearing age or pregnant women
• Validation of diagnostic codes, such as DSM-5 Alcohol-Related Neurodevelopmental Disorder (ND-PAE) diagnostic criteria or ICD-9-CM/ICD-10-CM medical coding classifications for Fetal Alcohol Syndrome (dysmorphic)
• Patterns of risky drinking among prenatally exposed adolescents and emerging adults
• Examination of effects of appropriate medical and developmental interventions for FASD-affected individuals, their parents and teachers, on mitigating alcohol-related outcomes, including chronic disorders
• Transgenerational and epigenetic effects of prenatal alcohol exposure

Gene - Environment Interplay

Many studies have sought to determine how environmental exposures moderate heritable behavioral traits and outcomes, such as excessive alcohol use. NIAAA encourages research to advance understanding of etiological mechanisms through which environments and genes contribute to individual- and population-level differences in alcohol use initiation, escalation and progression toward alcohol dependence and associated problems. Influential environmental factors may include broad social structures (macro environment), such as: urban or rural residence, level of residential stability, or neighborhood disorder, or local alcohol policies. More proximal, situational effects (micro environment) may include level of social inequity, norms exhibiting social constraints on drinking behaviors, familial and peer networks, or targeted intervention components. The influence of multiple genes on a range of individual-level factors may interact with environments (GxE interaction) to produce alcohol-related outcomes. New knowledge can be gained in part from utilizing data harmonization and systematic pattern recognition in secondary analyses powered by combined large and small datasets across current and previously-funded studies.

Investigators are encouraged to use approaches that examine the complex effects of varied combinations of episodic and cumulative clusters of experiential events exerted on individual behavioral choices that vary from individual to individual or within racial/ethnic subgroups and across progressive stages of development. These approaches are potentially advantageous for exploring alcohol-related behavioral and environmental exposure phenotypes, and biological endophenotype markers for alcohol use disorders and to inform development of targeted preventive and therapeutic interventions. Development and utilization of new methods and research designs ultimately can be enhanced by fostering collaborations across investigators and scientific disciplines. A variety of approaches for examining gene-environment interplay in analyses of existing data may include, but not be limited to the following:

• Use or development of a common metric of alcohol-related phenotypic and environmental measures across study designs
• Use of spatial analysis techniques to enhance the specificity of exposure measures, especially as individuals move across time through different levels of micro- and macro-environments
• Use of novel statistical or systems-based computational modeling techniques when pooling and harmonizing measures across independent small and large longitudinal studies
• Choosing genetically informative designs that help to overcome methodological challenges in GxE studies such as: scale of measurement, type I errors, non-replication, inadequate power, and population stratification
• Appropriate choice of genome-wide, hypothesis-free approaches to identify risk genes and integration of biologically plausible measures into theoretical models of vulnerability and AUD trajectories (see also Human Genetics and Genomics Research objectives)
• Meta-analytic approaches combining genomic and phenotype measures across multiple studies

Human Genetics and Genomic Research

Over the past decade there has been tremendous advancement in the genomic technologies especially in DNA sequencing. These technologies enable the production of millions of data points per sample such as single nucleotide polymorphism (SNP) genotyping with DNA chips with speed and accuracy and at relatively low cost. Despite real challenges with storage, management and analyses of such high volumes of data, these new high throughput technologies have advanced the field of human genetics and enabled the sequencing of unique samples to study the genetic risk factors of alcoholism.

There is a delicate balance between the amount of genetic and phenotypic information needed to be successful in identifying small effect loci. Even with advancements in biotechnology allowing the production of genotypes at lower cost and higher throughput, the challenge remains that small effect sizes demand large, well-phenotyped sample collections.

Since the mid-late 2000s, the focus has shifted to GWA studies. GWAS are powerful for homing in on alcoholism relevant areas of the genome in an unbiased way by comparing frequencies of commonly occurring single nucleotide polymorphisms (SNPs) between groups of individuals with specific characteristics. Genetic variants on the earlier generations of SNP platforms generally did not contain SNPs with less than a 10% minor allele frequency (MAF) to allow for greater likelihood of detecting a difference among the cases and controls if it existed. Through GWAS, genetic variants contributing to the development of several hundred disorders have been detected (www.genome.gov/gwastudies/). Although there are some GWAS successes in alcoholism, not all alcohol related phenotypes have shown strong genetic association, which may be due to a variety of factors such as sample size, power and confounding effects.

Lastly, it is well known that GWAS of complex human disorders demand a very large sample to provide enough power to detect most of the variations contributing to such phenotypes. Generating enough samples generally requires more than one study can provide. Approaches such as using studies within dbGaP and the establishment of consortia are tackling these barriers. One of the major goals of these consortia (e.g., Psychiatric Genomics consortium or PGC) is to combine samples from around the world to perform meta-analysis on a variety of phenotypes.

GWAS successes have been limited by gaps in the analytic tools and the completeness of the datasets obtained. GWAS methods combined with a growing number of other powerful genetic approaches are needed to understand complex genetics. Combined approaches will continue to identify more genetic variation (missing heritability) associated with the risk of complex disorders, including alcohol and drug abuse. A variety of approaches that could be used to reanalyze the existing genetic and genomic data sets related to alcohol use disorder may include, but not be limited, to the following:

• Use or development of new genetic analysis methods such as pathway and network analyses
• Use of new methods to relate GWAS data with brain expression data and their relationships
• Use of new bioinformatic tools to perform cross spices genomics or comparative genomics
• Use or development of new eQTL genetic analysis methods using existing data

Other Topics

Applications proposing to use existing data to achieve progress in other areas of alcohol epidemiology, prevention and genetics research are also encouraged under the terms of this announcement. Applicants may also use secondary analyses to address emergent research questions in College Drinking, Health Disparities, Public Policy Impacts, Screening and Brief Intervention, and Longitudinal Trajectories of Drinking Behavior.

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

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

Higher Education Institutions

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

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

• 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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) 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.

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, with the following modification:

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

Appendix:

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

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

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.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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

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

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

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

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or 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?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

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

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

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

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

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review}, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
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

Marcia S. Scott, Ph.D. (FASD, Gene-Environment Interplay)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-6328
Email: [email protected]

Abbas Parsian, Ph.D. (Human Genetics and Genomic Research)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-5733
Email: [email protected]

Wenxing Zha, Ph.D. (Methodology, Measurement and Other Topics)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0633
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

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

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

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