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

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

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

Purpose

Opioid use disorder (OUD), which includes periods of uncontrolled use, abstinence and relapse, results from a series of vulnerabilities to different stages of use (e.g. initial/acute use, escalation of use, acquisition of tolerance, dependence, uncontrolled use, abstinence and relapse or recovery) that occur throughout the lifespan of someone who misuses opiates. Each of these vulnerabilities most likely has multiple causes, including genetic and environmental components. In addition, there is mounting evidence that opiates themselves can alter how genes are turned on and off in specific brain regions, which may contribute in an epigenetic manner to downstream vulnerabilities of OUD. A major challenge in preventing OUD is to identify the molecular (epi)genetic insults that occur early in disease progression, at timepoints where interventions could prevent OUD. Genetic studies of people with OUD typically focus at the end stage and are likely muddied by the cumulation of these various genetic and environmental insults to the point where only the strongest genetic signals appear in a population. While increasing the number of individuals in a study can improve detection of genetic signals, these types of studies represent the population average, not the genetic underpinnings of any one individual with OUD.

In humans, polygenic risk score calculations can stratify risk for individuals, but cannot parse out the molecular genetic pathways and environmental insults that shaped an individual’s trajectory from their initial exposure to opioid use disorder. One way to tease out the molecular genetic pathways associated with early stages of OUD is to study individual phenotypes (or vulnerabilities) associated with OUD using animal models.

Although mice have been extensively used in genetic studies, the rat has traditionally been used to understand the neurobiology and behavioral phenotypes of OUD and other substance use disorders in humans. Rat genetic models are gaining traction and it is relatively easy to design studies to assess rat behaviors associated with many of the discrete vulnerabilities that occur on the trajectory of opioid use disorder. Since OUD is a complex brain disease, it is likely that multiple molecular genetic variants contribute to these individual behaviors at these different stages, and the culmination of these allelic variants, along with environmental insults that alter gene regulation, culminate in OUD. This rich behavioral knowledge, coupled with new genome editing methods, positions the rat as an emerging model to uncover the genetic and molecular genetic underpinnings of opioid use disorder.

Goals:

There are two main goals of the Rat Opioid Genome Project (ROGP). The first goal is to identify genetic, genomic, and molecular (epi)genetic variants that underlie phenotypes associated with vulnerability to distinct stages along the opioid use disorder (OUD) trajectory (e.g. initial/acute use, escalation of use, acquisition of tolerance, dependence, uncontrolled use, abstinence and relapse or recovery). The second is to identify genetic, genomic, and molecular (epi)genetic variants underlying phenotypes of conditions associated with OUD (e.g. respiratory depression, hyperalgesia, constipation, urinary retention, etc.). This research is expected to facilitate the discovery of targets for intervention and guide the development of individualized therapeutics to treat different aspects of OUD.

Applications that are not responsive to this FOA will be withdrawn without review. Applications that propose studies that only examine psychiatric disorders will not be considered responsive and will be withdrawn without review.

To be responsive to this FOA, the major thrust of the proposed project MUST:

• Propose studies that use an appropriate opioid or opiate, as determined by the scientific question.
• Propose and justify projects framed to identify genetic, genomic, and molecular (epi)genetic variants underlying rat phenotypes along the OUD trajectory (e.g. initial/acute use, escalation of use, acquisition of tolerance, dependence, uncontrolled use, abstinence and relapse or recovery) and/or sequelae of OUD (e.g. respiratory depression, hyperalgesia, constipation, urinary retention, etc.).
• Propose studies that examine at least two levels of genetic architecture (e.g. DNA sequence and epigenetic mark(s), splice variants and DNA level data, RNA sequence and epigenetic mark(s), etc.) and/or studies that probe the gene networks underlying the proposed phenotypes.

Applicants are encouraged to contact program staff to answer any questions they may have and are encouraged to consider the following when designing their proposed projects:

• Interdisciplinary teams may be necessary for successful completion of the proposed work. Such teams may include expertise in rat genetics, behavioral phenotyping, phenotype analyses, bioinformatics, data analysis, network analyses and modeling.
• Applicants may justify and propose to conduct genetic studies of more than one phenotype along the OUD trajectory and OUD sequelae
• Applicants may include studies that incorporate environmental stressors.
• Applicants should propose to create tissue banks for unused tissues for the benefit of the community.
• Applicants should describe how they will leverage existing databases and capitalize on existing resources to maximize the impact of their project.
• Applicants should demonstrate through appropriate preliminary data, that they are capable of conducting the proposed studies.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not 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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

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

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

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

The letter of intent should be sent to: [email protected]

Applicants are encouraged to send the letter of intent by email to the above email address. As an alternative, letters may also be sent to:

Office of Extramural Policy and Review
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Suite 4243, MSC 9550
Bethesda, MD 20892-9550

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.

Include support for up to six team members for travel to the NIDA Genetics and Epigenetics Cross-Cutting Research Team Meeting and the NIDA Animal Genetics Meeting, which is held annually over 3 days in the Bethesda area.

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: The overall goal of the Rat Opioid Genome Program is to uncover the genetic architecture underlying discrete phenotypes at early stages of disease progression and in sequelae associated with OUD. Describe the specific aims of the U01 for the performance period of this project.

Research Strategy:

Describe the significance of the behavioral and other phenotypic assays and how they will help to uncover the underlying genomic architecture (e.g. DNA variants, methylation variants, copy number variants, structural variants, etc.) of the genes and genetic domains involved in phenotypes associated with opioid use disorder. Describe the relevance of the phenotype(s) to opioid use disorder and the heritability of the phenotype(s). Describe how/why understanding the genetic architecture of this phenotype will advance the understanding of OUD and/or advance the field of research.

Describe how the methods will lead us to a deeper understanding of the genomic factors involved in opioid use disorder. Describe how the team has been chosen to capitalize on the available rat resources. Describe the qualifications of each team member and how they contribute to meet the goals of the project. Describe research management plans including plans for interacting with the NIDA Animal Genetics Consortium.

Describe the scientific premise for choosing the phenotypes along the OUD trajectory and the comorbid conditions. Describe each assay and why it was chosen. Describe the numbers of animals needed, the strains used and the rationale for using these animals. Include a power analysis indicating the estimated number of animals needed. As needed in your application, describe which tissues will be used for the various assays and include information about tissue handling, library preparation, types of cells and transcripts expected to be assayed, previous success conducting proposed studies, and potential pitfalls and alternative approaches.

Describe how the team will develop and use common metadata and data standards, adopt data quality metrics, analyze omics and other data, and share protocols and data with the scientific community, as appropriate and consistent with achieving the goals of the program. Describe any methods that need to be developed and/or implemented for data integration. Describe any innovative analysis strategies that will be used. Describe how the project proposes to take advantage of synergystic resources already available.

Provide a timeline and delineate annual milestones for the project. Milestones should be Specific, Measurable, Attainable, Relevant, and Timely. Applicants must describe the total number of animals and total number of phenotypic, molecular and data-driven assays that will be completed for each year of the project period and by the end of the project period. Applicants should also indicate the total number of samples from each group that will be assayed by the end of the project period. If selected for funding, applicants will work with NIH staff to develop more granular quarterly milestones. Applicants should plan for PDs/PIs and essential team members to travel to the Annual NIDA Animal Genetics Consortium meeting and indicate plans to join and participate in the NIDA Animal Genetics Consortium, which meets monthly.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• A primary goal of this program is to facilitate discoveries by the broad scientific community. Restrictive sharing practices and licensing terms for program-generated data and resources could substantially diminish their value and public benefit. Accordingly, awardees are expected to manage data, resources, protocols, and software in a way that achieves this goal.
• Data will be made available through appropriate portals and applicants will designate a central data repository for information regarding data, critical tools, protocols, and reagents developed by this program.
• ROGP program data will also be deposited into appropriate public or controlled-access data repositories. Applicants should identify such repositories and describe plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution consistent with achieving the goals of the program.
• Genomic Data Sharing Plan: If applicants propose to generate genomic data, they must indicate their willingness to abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data sharing plan.
• Sharing within the ROGP Program and the NIDA Animal Genetics Consortium: The ROGP program aims to maximize the benefits of sharing, while protecting the intellectual property of the data generators. Prepublication sharing of data within the NIDA Animal Genetics Consortium will allow collaboration across initiatives and further program progress towards its goals and objectives. Therefore, this program expects that data, metadata, and resources generated be made available to other NIDA Animal Genetics Consortium members immediately upon being considered "shareable", as appropriate and consistent with achieving the goals of the program. When program-generated material under embargo is shared within the program, it will be considered confidential with the understanding that the information will not be used or disclosed by program members unless explicitly agreed upon by the originator of the data under mutually acceptable terms. That is, consortium members may not publish using material generated by other consortium members without a collaboration or other agreement, or until the material in question has been made available to the public or until 12 months has passed, whichever is earliest.
• Applicants are expected to register resources supported by this FOA in the Neuroscience Information Framework (https:/neuinfo.org) and use Research Resource Identifiers (RRID) assigned by https://scicrunch.org in any publications supported by this FOA.

Sex as a Biological Variable: Behavioral studies from animal and human laboratory studies as well as field and treatment studies have found difference in males and females in phenotypic characteristics along the trajectory to OUD. Applications under this FOA should incorporate those phenotype differences into the study design and power the study to detect differences between males and females in outcomes. Incorporating sex as a biological variable is an NIH requirement, but does not demand statistical power to detect differences between males and females. In the case of this FOA, when the literature predicts sex differences in outcomes, powering studies to detect those differences is an important component of rigor and reproducibility.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 and responsiveness by NIDA, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the proposed study transform our ability to understand the genetic, genomic and/or molecular (epi)genetic factors that contribute to discrete stages along the OUD trajectory or to phenotypes that can be used to develop new therapeutics for treating people with OUD? Will the study advance our ability to understand and develop new therapeutic approaches to treat opioid use disorder?

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 team have appropriate expertise in rat genetic models of opioid use disorders? Does the team have experience in phenotyping the proposed behaviors and phenotypes? Does the team have appropriate expertise in omics data analysis and other proposed studies?

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? Do the proposed studies incorporate innovative strategies to identify genetic, genomic, and/or molecular (epi)genetic factors involved in opioid use disorders? Does the team propose to use novel methods to identify gene networks?

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

Is the overall strategy appropriate for accomplishing the proposed aims of the project? Does the team have access to the animals and tissues required for the proposed experiments? Is the proposed data analysis plan and/or pipeline appropriate? Does the team propose to take advantage of synergistic resources, such as data repositories and other NIDA-supported resources that are available? Is the projected timeline feasible and appropriate? Are the proposed milestones quantitative and appropriate for each phase of the project?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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.

Not Applicable

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

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

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

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

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

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned 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 National Advisory Council on Drug Abuse. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

If you are preparing a Cooperative Agreement FOA, use this document to complete the optional portions of the Cooperative Agreement text below. Then, copy and paste all the text into the FOA in the Cooperative Agreement section where indicated.

Visit the Cooperative Agreement (CA) Kiosk at http://nih-extramural-intranet.od.nih.gov/d/nih/topics/coop/index.htm for more information on developing Terms and Conditions of Award and a justification memoranda for the use of the cooperative agreement mechanism to be submitted to OEP for approval.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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 awardees 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 PD(s)/PI(s) will have the primary responsibility for:

• Determining research approaches, designing protocols, setting project milestones, and conducting research
• Participating in group activities, including the NIDA Animal Genetics Consortium, and subcommittees as needed
• Submitting all data to a mutually agreed upon publicly available resource as soon as they are collected for quality control
• Preparing abstracts, presentations and publications and collaborating within the NIDA Animal Genetics Consortium in making the public and professionals aware of the program
• Assessing and disseminating data, protocols, and methods developed for or derived from the ROGP program within and outside the NIDA Animal Genetics Consortium
• Adhering to policies regarding data sharing and publication established by the NIH and NIDA Animal Genetics Consortium
• Abiding by common definitions, protocols, and procedures, as chosen by majority vote of the NIDA Animal Genetics Consortium
• Submitting periodic progress reports in a standard format, as agreed upon by the NIDA Animal Genetics Consortium
• Attending and participating in NIDA Animal Genetics Consortium meetings and accepting and implementing decisions by the NIDA Animal Genetics Consortium, as appropriate
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NIH Project Scientist(s) will have substantial scientific involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. The Project Scientist(s) will participate as members of the NIDA Animal Genetics Consortium. The Project Scientist(s) will have the following substantial involvement:

• Participating with the other NIDA Animal Genetics Consortium members in addressing issues that arise with planning, operation, assessment, and data analysis.
• Serving as a liaison, helping to coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the awardees. The Project Scientist(s) will also help coordinate the efforts of the NIDA Animal Genetics Consortium with other groups conducting similar efforts
• Attending all NIDA Animal Genetics Consortium meetings as a voting member, assisting in developing standard operating procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) will be responsible for working with the grantees as needed to manage the logistic aspects of the award
• Reporting periodically on progress to the NIDA Animal Genetics Consortium
• Serving on subcommittees of the NIDA Animal Genetics Consortium as appropriate
• Assisting awardees in the development, if needed, of policies for dealing with situations that require coordinated action
• Providing advice in the management and technical performance of the award
• Assisting in promoting the availability of the data and related resources developed by the award program to the scientific community at large
• Participating in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through the program
• Other NIH staff may assist the awardee as designated by the Program Official

Additionally, an agency Program Official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Prior to funding an application, the Program Official will contact the applicant to discuss the proposed milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official will negotiate with the applicant and agree on a final set of approved milestones which will be specified in the Notice of Award. The NIH Program Official, in consultation with the Project Scientist, will determine if the awardee has met the milestones required for each year of funding.

NIH reserves the right to withhold funding or curtail an award in the event of:

• Substantive changes in the project, or failure to make sufficient progress toward the work scope with which NIH concurred, or
• Ethical or conflict of interest issues
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage and assess the project. The awardees and the Project Scientist(s) will meet in person with NIDA Animal Genetics Consortium yearly and on monthly conference calls as needed to share information on methodologies, analytical tools, and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.
• The NIDA Animal Genetics Consortium will serve as the main scientific body of the program.
• The NIDA Animal Genetics Consortium may establish subcommittees as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The NIDA Animal Genetics Consortium will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.

The ROGP awardee agrees to work collaboratively to:

• Provide for secure, accurate and timely data submission.
• Participate in presenting and publishing new processes and substantive findings
• Assess and disseminate ROGP data and resources
• Participate in the governance of the NIDA Animal Genetics Consortium
• Interact with other relevant NIH activities, as needed, to promote synergy and consistency among similar projects.

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Amy C. Lossie, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6092
Email: [email protected]

Dharmendar Rathore, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-6965
Email: [email protected]

Cheryl Nathaniel
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6703
Email: [email protected]

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

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