Required Application Instructions

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

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

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

Vulnerability to substance abuse and addiction has a heritable component. Recent advances in gene sequencing technologies have substantially enabled the identification of gene variants that accompany phenotypes associated with addiction. Classic behavioral genetics studies have shown that alleles influencing addiction-related phenotypes can be enriched by selection in model organisms, providing the basis for the discovery of genes influencing the defined phenotype. The use of selectively bred animals also provides an opportunity to identify targeted and measurable aspects of physiology and brain function that influence behavior, and phenotype-genotype relationships that are important for addiction. In addition, by combining resources from selective breeding with newly discovered genetic and genomic technologies, it is possible to elucidate the effects of environmental exposures and drug exposures on animals of a defined genotype. Presently, the identities of gene variants that mediate behavioral differences in selectively bred organisms remain largely unknown, greatly limiting the interpretation of physiologic differences and the understanding of environmental effects on drug abuse, and hindering the translation of genetic findings to humans and other model organisms. Meanwhile, new technologies in Next-Gen Sequencing, array-based genotyping, functional genomics and informatics have now made it possible for genome-wide survey, discovery and validation of functional loci and gene variants responsible for the heritability of these traits.

An alternative approach to selective breeding for identifying genetic variants responsible for addiction related traits is to conduct whole genome wide association analyses in outbred populations of animals. This is made possible by the dramatic reduction of the cost of both SNP based genotyping and DNA sequencing. This FOA supports such approaches using outbred animal models; however, a sufficiently large number of outbred organisms will be needed to discover new genetic variants in whole genome wide association studies.

This announcement encourages applications for projects aimed at the discovery of gene variants in outbred or selectively bred non-human animals through the use of Next-Gen Sequencing technologies. The proposed projects should be based on data demonstrating the relevance of the traits to drug abuse behaviors and processes of addiction. Investigators may employ previously selectively bred animals, re-derived strains, strains selected for some specific new phenotypes, beginning with a novel progenitor population, or an outbred population. Vulnerability phenotypes, for purposes of this FOA, are defined as individual differences that convey increased propensity to acquire, maintain or escalate to uncontrollable, compulsive drug intake, or increased vulnerability to relapse to drug seeking and drug-taking following a period of abstinence. Vulnerability phenotypes may be defined behaviorally or neurobiologically, must have demonstrated heritability, and be suitable for mapping in outbred or selectively bred strains. The following are examples of vulnerability phenotypes that have been characterized behaviorally which would be appropriate for study; however, this is not an inclusive listing and there may be others:

• High drug sensitivity, reactivity or preference
• Preference or sensitivity for non-drug rewards
• Somatic and affective drug withdrawal
• Novelty preference or novelty seeking
• Increased incentive motivation for reward-related stimuli
• Sensitivity to develop escalation of drug taking
• Impulsivity
• Poor cognitive flexibility (e.g., reversal learning, set shifting, etc.)
• Resistance to punishment during drug-seeking
• Persistent responding in the absence of drug
• Heightened relapse and reinstatement
• Enhanced stress reactivity
• Disrupted circadian rhythms

Vulnerability phenotypes that have been identified by individual differences in neurobiological substrate or mechanisms (structural, functional, chemical) that can be genetically mapped are also appropriate.

Mapping of genetic modifiers of vulnerability phenotypes in knockout or knock-in animals, i.e. identification of gene variants that modify a drug abuse associated phenotype when a knockout or knock-in animal or defined mutation is bred into a different genetic background, is also responsive to this FOA.

Investigators are strongly encouraged to discuss their applications with the Scientific/Research contact listed in this FOA before submission.

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 https://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.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.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org). Please see NOT-DA-12-008 for further details.

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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

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

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

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:

Specific Aims: List the objectives and goals of the proposed program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy:

Propose a hypothesis driven research strategy. The application should address the following:

Selected Breeding-Strategy

For investigators using a selected breeding-phenotyping strategy:

• Demonstrate that the trait is heritable.
• Provide data that support the map-ability of traits and estimates of the number of genetic loci for the trait.
• Estimate the power needed to identify gene variants associated with the selected trait(s).
• Define the genetic architecture of the trait.
• Address the problem of random fixation depending on breeding strategy used.
• Explain the overall strategies, methodologies, and analyses for breeding and mapping a trait or phenotype.
• Justify the selection or breeding strategy. Initial genotyping such as marker assisted breeding or sequencing may be used to assist in the breeding or mapping strategy.
• Describe methods to purify high quality RNA (if RNA seq is used) and methods to purify high quality DNA
• Describe the analytical plans for data analysis and interpretation of the results.
• Provide milestones for achieving the aims of the project

Genome Wide Association Strategy

For investigators proposing a genome wide association approach:

• Provide evidence that the trait is heritable.
• Provide data that supports the map-ability of traits
• Harmonize phenotypes across multiple studies if a consortium is established to generate sufficient power to map the trait of interest.
• Estimate the power sample size needed to map the trait.
• Address strategies to deal batch effects, if behavioral assays and sequencing are done over a period of time.
• Describe the genotyping and platform to be used.
• Describe methods to purify high quality RNA (if RNA seq is used) and methods to purify high quality DNA
• If a consortium is established, describe plans for managing the consortium by explaining the decision making process and how decisions are communicated across the consortium. Also describe how conflicts would be resolved.
• Describe the analytical plans for data analysis and interpretation of the results.
• Provide milestones for achieving the aims of the project

Sequencing:

For DNA sequencing, whole genome/exome/targeted methods should be described including the method and product used for sub-genome enrichments if exome and targeted approached are to be used, and the sequencing platform should be described. The average coverage for the sequencing should also be specified. For investigators proposing targeted capture experiments, the coverage is expected to be >40x coverage. If whole genome sequencing is proposed, investigators are expected to propose at least 20x coverage. The method for variant calling, sequence alignment, and efficiency of querying gene variants should be described. The method used to assess sequence quality and accuracy should be described. The investigator should also describe the analyses, the tools to store reads, assemblies, variants, and annotation of sequence data. The investigator should also describe the analyses and tools to store reads, assemblies, variants, and annotation of sequence data. Investigators should explain how results will be interpreted. A discussion of the implications of the successful accomplishment of these goals for the proposed study should be included.

As part of this announcement investigators may describe plans to use the Next-Gen sequencing and genotyping resources of The Center for Addictions Genomics (TCAG) in the NIDA/NIAAA intramural program. (See Letters of support)

Letters of Support. A letter from Dr. David Goldman or Dr. Colin Hodgkinson is required if the resources of The Center for Addictions Genomics (TCAG) in the NIDA/NIAAA intramural program are planned.

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 submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html, as applicable
• Investigators are expected to deposit selectively bred strains in an appropriate repository and register these strains and any research resources supported by this FOA in the Neuroscience Information Framework http://scicrunch.com/resources.
• Investigators are expected to deposit sequence data in a public data base. The location of the public data base, where the sequence data will be deposited, should be identified.

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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review at the 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 NIH program staff 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 our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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? 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? 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?

Is the trait heritable? Does the application provide data supporting the map-ability of traits? Is mapping strategy justified and appropriate? Does the investigator address strategies to overcome pitfalls associated with the chosen mapping strategy? Is the sample size sufficiently powered to identify gene variants? Are sufficient details provided regarding data collection of the phenotype? Is the method to measure the phenotype valid? If behavioral assays are conducted over time, how are batch effects addressed? Are the analytical plans for data analysis and interpretation provided and are the plans valid? Are the milestones and management of the project adequate?

Is the genotyping and sequencing strategy sufficient to identify causal genetic variants? Is a strategy for following up on any identified sequence or genotype hits provided? Are the methods for generating high quality DNA and RNA satisfactory? Is the DNA sequencing the sequencing approach (whole genome/exome/targeted) defined? Is the sequencing and genotyping coverage adequate? Are the methods for variant calling, sequence alignment, and efficiency of querying gene variants valid? Is the method used to assess sequence quality and accuracy valid? Will the analyses and tools to store reads, assemblies, variants, and annotation of sequence data yield sound results?

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 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.

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 its currently 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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 National Institute on Drug Abuse , 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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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

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

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

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

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

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

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.

NIDA will conduct each year an administrative review of achievement of milestones. Should milestones not be achieved NIDA reserves the right to reduce the amount of the award.

Cooperative Agreement Terms and Conditions of Award

These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardee is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The Program Director/Principal Investigator (PD/PI) will have the primary responsibility for:

i) The PD/PI will have the primary responsibility for all aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The PD/PI agrees to accept close coordination, cooperation, and participation of NIDA staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.

ii) Annual progress reports will inform on the grantee's progress of the project or projects conducted under this award, including progress, obstacles and steps taken to remedy them, and a summary of any NIDA-approved changes and departures from the approved study protocol.

Milestones for each study will follow the timeline proposed and agreed upon between the grantee and NIDA Program staff.

iii) Awardees who do not accomplish the negotiated milestones shall submit a milestone report which will include a discussion of why the milestones were not met in the agreed- upon timeframe, and propose a corrective action plan in consultation with the Program Official and Project Scientist. The corrective action plan shall include amended milestones, plans to achieve the amended milestones and any additional items required by NIDA staff. The plan shall be provided to NIDA staff no later than 2 months following the missed milestone. The inability of the awardees to meet agreed-upon milestones may result in an adjustment of funding and possible termination of the grant.

Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDA.

NIDA Staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

i) Program Official: A NIDA program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIDA Program Official, who will not participate in the research or the preparation of publications, will be responsible for monitoring the conduct of the project. The Program Official carries primary responsibility for: (1) periodic review and monitoring and approval of the progress of the research plans in relation to their stated objectives, including consistent communication with the PI and requests for additional reports or documentation; and (2) making recommendations regarding continuance of the program. The Program Official will receive all required progress reports to determine that satisfactory progress is being made and will work collaboratively with the NIDA Grants Management Specialist to assure high quality business management of the program, including the most effective use of grant money provided through this cooperative agreement.

i) Project Scientist: In addition to the Program Official who will be responsible for normal program stewardship, the cooperative agreement will be assigned a Project Scientist (PS) with expertise in genetics. The PS will be substantially involved in this project beyond the normal stewardship of an NIDA Program Official by ensuring the established studies are followed and assisting in overseeing the quality of the study. The Project Scientist be substantially involved as an active partner in those aspects of the scientific management of the project indicated by the Terms and Conditions, including protocol development, quality control, interim data monitoring, final analysis, and selection of animal models for sequencing. This level of involvement will be above and beyond the levels typically required for administration of traditional research grants and is vital to the success of this program. However, the lead responsibility for refining the design of the project and carrying it out will rest with the Principal Investigators. The additional responsibilities of the project scientist are to:

1) Assist in the development of revised breeding strategies should changes in genomic technology require modification of the design of breeding protocols and sequencing strategies for genetic mapping a phenotype.

2) Assist in developing a strategy for following up on any identified sequencing hits.

3) Provide advice on best practices for data cleaning and analytic methods for associating a gene variant with the phenotype of interest, and interpretation of the data.

4) Assist in coordinating a multisite effort if outbred animals are used to conduct a genome wide association analysis.

NIH Intramural Scientist: The PD/PI may enlist an NIH Intramural Scientist to have a substantial scientific involvement as a key co-investigator in the extramural research project.

ii) Program Staff act as a resource to aid in resolving scientific’s as they arise.

iii) Study Closure - NIDA may require that a study be closed for reasons including but not limited to: failure to complete milestones and b) emergence of new information that diminishes the scientific importance of the study question. Once notified by the Grants Management Branch, NIDA, of site closure or that the study should cease, only reasonable personnel and administrative costs associated with the orderly phase-out of the study or site may be obligated or charged to the grant award.

Areas of Joint Responsibility Include:

i) The awardee and NIDA program staff will confer on the most optimal strategy to conduct breeding to map genetic loci or develop optimal strategies for identifying genetic loci in outbred animals.

ii) Any changes in the experimental design for mapping genetic variants will be discussed between the awarded and program staff before a decision is made in a change in experimental design. Both parties shall agree on the most appropriate experimental design and outcome.

iii) Status reports in the format of web conference calls with NIDA program staff will take place on a bi-monthly basis. Awardees are expected to have video capabilities so NIDA program staff can visually interact with the PI. The PI will provide a report describing progress and obstacles toward achieving the yearly milestones as well as any proposed changes in experimental design.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: https://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-945-7573
Email: GrantsInfo@nih.gov

Da-Yu Wu, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-4649
Email: wudy@nida.nih.gov

Gerald McLaughlin, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5819
Email: gmclaughlin@nida.nih.gov

Edith Davis
National Institute on Drug Abuse (NIDA)
Telephone: 410-360-4734
Email: edavis1@nida.nih.gov

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.