Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Drug Abuse (NIDA) National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Funding Opportunity Title	Gene-Environment Interplay in Substance Use Disorders (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	Reissue of PA-07-415
Related Notices	February 5, 2015 - This PA has been reissued as PA-15-112. July 31, 2014 See Notice NOT-DA-14-020. Expiration date extended for this PA. June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PA-11-236
Companion FOA	PA-11-235, R01 Research Project Grant, and PA-11-237 R03 Small Grant Program
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.279, 93.273
FOA Purpose	The National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism seek to stimulate and expand research on the interplay of genetic and environmental factors in the genesis, course, and outcomes of substance and alcohol use disorders (SUDs). Previous work in genetic epidemiology and molecular genetics has established that SUDs are highly heritable, developmental disorders with important genetic substrates. Building on these findings, new studies using genetically informative approaches are needed to elucidate the complex interplay of genetic and environmental factors in developmental trajectories of SUDs and comorbid conditions, deepen and refine phenotypic definitions of SUDs, and meet the methodologic challenges of the field. Such studies hold great potential to promote understanding of the true contributions of both genetic and environmental factors to initiation, progression, comorbidity, adverse outcomes, and desistance of SUDs; to elucidate mechanisms of risk; and to enhance opportunities for translation to treatment, prevention, gene-finding and molecular studies.

Posted Date	July 19, 2011
Open Date (Earliest Submission Date)	September 16, 2011
Letter of Intent Due Date	Not applicable.
Application Due Date(s)	Standard dates apply, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Standard dates apply, by 5:00 PM local time of applicant organization.
Scientific Merit Review	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date(s)	Standard dates apply
Expiration Date	New Date January 8, 2015 per issuance of NOT-DA-14-020. (Original Expiration Date: September 8, 2014)
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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

Background

Research applying genetic epidemiologic and molecular genetic approaches have contributed increasingly significant advances to our understanding of the causes of use, abuse, and dependence of addictive substances, including alcohol, illicit drugs, and nicotine [Substance Use Disorders (SUDs)]. Genetic epidemiologic studies have established that SUDs are complex developmental disorders, with high heritability; shared environmental effects appear to be strong, particularly early in adolescence and at the points of drug use initiation. Genetic epidemiologic approaches have highlighted the roles of gene-environment interactions and gene-environment correlations in understanding SUD risk and trajectories. However, the descriptive nature of these studies has often limited their ability to explicate etiologic mechanisms. Molecular genetic studies have made exciting advances in identifying genes and gene variants that may contribute to the risk for SUDs, but without incorporating environmental factors into these studies, little of predictive or clinical value has yet emerged.

Building on these findings, new studies using genetically informative approaches are needed to elucidate the complex interplay of genetic and environmental factors in developmental trajectories of SUDs and comorbid conditions, deepen and refine phenotypic definitions of SUDs, and meet the methodologic challenges of the field. Gene-environment interplay encompasses studies of heritability, gene-environment interaction, gene-environment correlation, and epigenetics. Such studies hold great potential to promote understanding of the true contributions of both genetic and environmental risk factors to risk for initiation, progression, comorbidity, adverse outcomes, and desistance of SUDs; to elucidate the mechanisms of risk; and to enhance opportunities for translation to treatment, prevention, gene-finding and molecular studies.

In regard to developmental trajectories, further work is needed on the interplay of genetic, environmental, and developmental factors in transitions among stages of, and alternative pathways into and out of, substance use, abuse, dependence, persistence, and relapse. Developmental factors include gender differences, premorbid and comorbid conditions, physiological factors such as early puberty, and age of onset of alcohol and drug use; incorporating these into trajectory models carry important implications for developing targeted preventive interventions. Further work is also needed on the developmental and cognitive consequences of SUDs, to define who is at risk for adverse sequellae and who is more resilient, and on the interplay of genetic and environmental risk and protective factors. The impact of prenatal substance and alcohol exposures interacting with genotype, development, and later environmental conditions on later neurobehavioral deficits and fetal alcohol spectrum disorders remain areas of significant interest.

Several forms of gene-environment interplay have been described and all play key roles in understanding the mechanisms of risk for SUDs. Given the complex multifactorial nature of SUDs, studies of gene-environment interaction are needed to understand the contributions of both genetic and environmental risk factors to these developmental trajectories. Studies of gene-environment interaction can explicate underlying biological mechanisms and pathways to disorder, help identify genes that act through interaction but demonstrate only marginal main effects, explain and address heterogeneous results from prior studies by taking into account differences in exposure, and identify environmental factors that act on genetically susceptible individuals. Such findings in turn may have translational implications for predicting risk and eventually for tailoring effective interventions based on genotype, gene expression, and exposure.

While a large literature exists that describes correlations between environmental variables and risk for SUDs, studies of gene-environment correlations increasingly highlight the influences that genetic factors can exert over seeming environmental factors. Emerging evidence indicates that passive and evocative gene-environment correlations play a role in parenting behaviors, and active and evocative processes influence how individuals select their peer groups, drug exposures, and social environments; further studies are encouraged to help understand such gene-environment correlations and in turn help target preventive interventions appropriately. Studies are also encouraged that elucidate the influence of supportive vs. high-risk environments on outcomes in prevention studies of genetically vulnerable subgroups. Changes in the regulatory environment, such as increasing restrictions on tobacco products, variable enforcement of alcohol access to underage drinkers, and legalization of medical marijuana, merit study to evaluate differential response among genetically vulnerable subgroups.

Prior research has begun to make important contributions to the understanding of underlying phenotypes and endophenotypes for SUDs. Further studies of endophenotypes are needed that extend beyond electrophysiology, such as startle modulation endophenotypes; behavioral inhibition and possible internalizing (affective) phenotypes; and sleep (circadian rhythm) endophenotypes. Deep phenotyping can build on such findings to integrate and move beyond empirical identification of phenotypes and endophenotypes, to delineate the brain mechanisms underlying these behaviors and ultimately help identify genes that are linked to the specific brain processes that convey risk.

Further studies are needed to address the numerous methodological challenges that affect research on the gene-environment interplay in SUDs. The conditionality of SUDs (that development of drug or alcohol abuse and dependence, unlike other disorders, depends on exposure to drugs or alcohol and on initiation) is a key issue that impacts other aspects of this work, including the definition of an unaffected individual and of control groups (those who have never used vs. those who used without progressing to dependence), or missing data on etiology due to those at risk for dependence who never initiated use. The wide range of environmental factors and various ways of measuring and describing them poses particular challenges to studies of gene-environment interplay; approaches to the typology of environmental factors and to reducing the problems of Type 1 errors and multiple testing are needed. Another issue is testing alternative causal models; this approach can help move the field forward, and applicants are encouraged to consider this method in their proposals. More studies that focus on methodologic issues specific to SUDs (phenotype definitions and nosology, causal modeling, quantitative approaches) continue to be needed. Effective approaches to data harmonization to support the ability to combine data from multiple studies and enhance power are sought. The R21 mechanism may be particularly suited to address these gaps; it is intended to support exploratory, novel studies that break new ground or extend previous discoveries toward new directions or applications, or to support high risk high reward studies that may lead to a breakthrough in a particular area, or result in novel techniques, methodologies or models. Studies focused on methodologic challenges that can use the R21 mechanism may also respond to PAR-11-032 Methods and Approaches for Detection of Gene-Environment Interactions in Human Disease (R21) (http://grants.nih.gov/grants/guide/pa-files/PAR-11-032.html) Along with developing these sophisticated methodologic approaches, more biostatisticians and methodologists need to be attracted to and retained in applying their skills to existing questions and databases in drug abuse and alcohol research; information on mechanisms of support for training and career awards with NIDA can be found at http://www.nida.nih.gov/researchtraining/traininghome.html; and for NIAAA at http://www.niaaa.nih.gov/ResearchInformation/ExtramuralResearch/Pages/default.aspx#training.

Applicants are strongly encouraged to consider cost-effective approaches in their genetic epidemiologic proposals. A variety of genetic epidemiologic databases already exist, including some with genotyping data, and studies applying secondary analyses to these data are encouraged. Other cost-effective approaches potentially using the R21 mechanism include the addition of appropriate measures and data analysis on genetic or environmental factors to ongoing studies which lack these data, gathering retrospective data on established samples, combining data across studies to increase power for research on understudied subsamples and on outcomes characterized by small effects, and innovative forms of data collection such as web-based methods. Each of these approaches poses challenges to the field, and appropriately sophisticated methodology needs to be proposed and developed. Proposals for secondary analyses may apply under the R03 announcement cited above, or under the announcements Accelerating the Pace of Drug Abuse Research Using Existing Epidemiology, Prevention, and Treatment Research Data (R01) http://grants.nih.gov/grants/guide/pa-files/PAR-10-018.html or Secondary Analysis of Existing Alcohol Epidemiology Data (R01) http://grants.nih.gov/grants/guide/pa-files/PA-08-167.html. General guidance for human genetics applications to NIDA can be found at http://www.nida.nih.gov/about/organization/Genetics/humanapp/index.html; proposals responding to this Program Announcement should consider those guidelines where appropriate. These include clarifying sample selection; research design; statistical power for main effects, correlations, and interactions; procedures for pooling data when appropriate; generalizability; phenotype selection; choice of instruments for assessing SUDs/AUD and comorbid conditions where appropriate. Researchers seeking to augment the collection or harmonization of phenotypic data in their genetic studies can find appropriate measures at https://www.phenxtoolkit.org/, and domains covered by the NIDA Genetics Consortium research can be found at http://www.drugabuse.gov/about/organization/Genetics/ngcdomains/ . Collaborations to combine data and enhance power are encouraged.

Proposals responding to this Funding Opportunity Announcement are expected to focus on the interplay of genetics and environment. Applicants seeking support for studies that focus primarily on the molecular genetics of drug abuse vulnerability are referred to the NIDA Funding Opportunity Announcements Molecular Genetics of Drug Addiction and Related Co-morbidities (http://grants.nih.gov/grants/guide/pa-files/PA-11-026.html); Expanding and Personalizing Treatment Options for Alcohol Use Disorders including Pharmacogenomics (R01) (http://grants.nih.gov/grants/guide/pa-files/PA-08-167.html); or Behavioral Regulation Mechanisms of Alcohol Dependence and Related Phenotypes (R01) (http://grants.nih.gov/grants/guide/pa-files/PA-10-255.html). Applicants seeking support for studies of basic functional genomic research are referred to the NIDA Program Announcement: Functional Genetics, Epigenetics, and Non-coding RNAs in Drug Addiction (http://grants.nih.gov/grants/guide/pa-files/PA-11-033.html). Any molecular genetic or functional genomic component included in applications under the present Funding Opportunity Announcement needs to be fully developed, with appropriate hypotheses and gene-identifying techniques. Further guidance, announcements and resources regarding NIDA’s program on the molecular genetics of drug abuse can be found at http://www.drugabuse.gov/Genetics/GeneticsHome.html.

Areas of interest

The following points represent areas and issues of interest to NIDA and NIAAA; applicants are not limited to these ideas:

• Studies of gene-environment interplay to elucidate etiologic mechanisms, including:
  • mechanisms contributing to comorbidity among psychiatric disorders and SUDs
  • underlying vulnerability factors and endophenotypes that may mediate risk, including neurophysiological and temperament studies
  • individual differences in propensity and severity of addictions
  • age of onset of substance use in the risk for later SUDs; the salience of initial drug or alcohol exposure (e.g. timing, type, amount, context, subjective and objective responses) for subsequent SUD risk and course; early use as an environmental factor interacting with genetic risk at a particular point in development; and the impact of prolonged exposure to psychoactive substances on the developing brain in adolescence
  • epigenetic mechanisms to explain gene-environment interaction and phenotypic plasticity alteration in the genesis and course of SUD

• Studies of the role of gene-environment interplay in dynamic phenotypes across the lifecourse, including:
  • genetic and environmental factors in vulnerability for onset, progression, persistence, withdrawal, sequellae, desistance, and relapse of SUDs
  • alternative phenotypes including affective or inhibited subtypes
  • genetic and environmental factors in the genesis of SUDs/AUD across racial, ethnic, and gender groups, and cross-cultural comparisons
  • gene-environment correlation, to clarify how individuals select and influence risky and protective environments, and to help identify true gene-environment interactions
  • refined and more systematic environmental measures, to identify salient environmental factors associated specifically with risk for SUDs; particular gaps include the roles of trauma and of horizontal risk transmission among peers and siblings
  • adverse outcomes in offspring exposed to drugs, alcohol or smoking in utero; pre- and postnatal genetic, epigenetic and environmental factors that may alter susceptibility and natural history of fetal alcohol spectrum disorders
  • sexual and drug use HIV-risk behaviors and in the acquisition of HIV-infection
  • genetic and environmental factors that influence drinking behavior in early, mid- and late adolescence
• Studies of specificity vs. general liability to substance abuse and dependence and to poly-substance abuse; heritability studies of understudied substances including stimulants and other prescription medications
• Studies that explore the interplay of genetic, environmental and developmental factors within substance abuse intervention outcomes studies, addressing issues including:
  • whether and how genetic variability accounts for differential effects of interventions
  • whether effective interventions focusing on social or other environmental elements work through altering gene expression
  • clarifying causal inferences by demonstrating changes in mediators related to outcomes of interest

Studies to clarify the role of environmental factors, including:

• explicating how familial or neighborhood environmental stressors, including but not limited to child abuse, interact with genetic risk factors in the trajectories of later SUDS, and how genetic and environmental protective factors might modify this risk
• surveillance research to evaluate the interplay of genetic influences and more restrictive or permissive regulatory environments in the onset and course of substance use behaviors

Methodological studies, including:

• improved statistical approaches, to combine or compare data from a variety of datasets, test alternative models and hypotheses, and describe the heterogeneity of SUDs
• research to improve definitions of control groups for SUD studies.

Funding Instrument	Grant
Application Types Allowed	New Resubmission Revisions The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	The combined budget for direct costs for the two year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.
Award Project Period	The maximum period is 2 years.

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

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) 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 must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) 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 SF 424 (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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

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

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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.

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All page limitations described in the SF424 Application Guide and the Table of Page Limits 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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

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.

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 SF 424 (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.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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.

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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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.

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

Reviewers will provide an overall impact/priority 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Innovation

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

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.

Renewals

Not applicable.

Revisions

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/priority score.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments 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/priority 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.

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 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Naimah Weinberg, M.D.
Division of Epidemiology, Services, and Prevention Research
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-1908
Email: [email protected]

Marcia S. Scott, Ph.D.
Division of Epidemiology and Prevention Research
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-6328
Email: [email protected]

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

Heidi Young
Grants Management Branch
National Institute on Drug Abuse (NIDA)
Telephone: 703-243-5024
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 45 CFR Parts 74 and 92

Special Considerations

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information see http://www.nida.nih.gov/about/organization/nacda/CouncilStatement.html.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www.nida.nih.gov/about/organization/nacda/CouncilStatement.html.