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

The purpose of this funding opportunity announcement (FOA) is to support projects developing technologies and tools to detect, quantify, and characterize HIV brain reservoirs and how they may be altered by exposure to substances of abuse.

Eliminating HIV infection is one of the top challenges for HIV research, but a critical obstacle that could hinder this effort is the existence of reservoirs of latent virus in the brain despite antiretroviral therapy. Central nervous system infection occurs very early during systemic HIV infection, and recent investigations suggest that very low levels of HIV RNA in the cerebrospinal fluid are associated with local immune activation. Evidence of latent and/or persistent HIV infection in the brain exists; however, there are many scientific and technical challenges that must be addressed to understand how best to eradicate the brain reservoir threat. In addition, chronic substance abuse often results in persistent brain changes that could impact the HIV reservoir, such as through epigenomic modification of integrated HIV provirus or transient activation of latently infected brain cells. Understanding the effects of drugs of abuse on HIV replication and latency within the brain is critical if we wish to induce a higher rate of remission or to eventually cure HIV in substance abusing populations.

This R21/R33 FOA is designed to support research that will advance the goals of detecting and quantifying latent viral reservoirs in the brain, and whether substances of abuse can alter the latent viral reservoirs. The objective of this FOA is to support projects developing technologies and tools to detect, quantify, and characterize HIV brain reservoirs, including HIV within macrophage/microglia, astrocytes, or within specific brain regions, and how these reservoirs may be altered by exposure to substances of abuse. The ability to monitor and quantify latent HIV in living human brains is one of the ultimate goals of supporting this work. It is, therefore, necessary to either improve our ability to detect and quantify HIV latent reservoirs in living human brain, and/or examine potential biomarkers of latent infection in the brain to determine if substances of abuse modulate the characteristics of the reservoirs. This initiative should help to establish important groundwork for the detection and eradication of HIV brain reservoirs in substance-abusing populations.

R21 Phase: The R21 phase of this initiative is meant to support creative and innovative projects developing technologies and tools to detect, quantify, and characterize HIV brain reservoirs and to determine how substances of abuse impact these reservoirs. In addition, this phase should focus efforts on establishing feasibility of using these techniques to measure HIV brain reservoirs in in vivo systems. In this phase, researchers may propose to develop their tool or biomarker using any in vitro, in vivo, or pre-clinical model. Applicants proposing to develop new technologies or to improve upon existing technologies for detecting and quantifying latent HIV cellular reservoirs in the human brain should consider approaches that aim to detect and quantify integrated proviral DNA that is capable of producing infectious virus. Sensitive techniques are required to differentiate between cellular DNA vs. viral DNA, between defective vs. replication competent proviral DNA, and between spliced vs. unspliced viral RNA as applicable.

Investigators are strongly encouraged to partner with HIV and substance abuse researchers and use any existing repositories and other resources as appropriate to the research aims. Note that the R21 phase of the application is not expected or required to establish these technologies in humans. Rather, the approach must include a clear rationale for how the technology can be advanced to human use in the R33 phase.

R33 Phase: The R33 phase must follow the R21 phase; it cannot be a stand-alone submission. Progress in achieving milestones will be administratively reviewed as part of the transition from the R21 phase to the R33 phase (see also, Section IV, 3. Reporting.)The subsequent R33 phase should emphasize advancing and using the tools and technologies developed in the R21 phase to detect, quantify, and characterize HIV reservoirs in human brain exposed to substances of abuse and antiretroviral therapy. In addition, the R33 phase should begin to investigate the underlying mechanisms by which substances of abuse modulate the quantity and characteristics of HIV reservoirs in the human brain. Substances of abuse of interest include: nicotine, stimulants, opioids (including prescription drugs), cannabinoids, or combinations of these drugs with alcohol.  Applications lacking either of these aspects will not be considered responsive to this FOA and will not proceed to review.  Applications focused solely on alcohol exposure will not be considered responsive to this FOA and will not proceed to review.

This FOA will support, but is not limited to, the following types of studies:

Development of technologies that track or measure latent viral reservoirs in real time to show any increases or decreases over time due to exposures to substances of abuse

Use of the developed technologies to determine if substances of abuse can affect the integrity of viral reservoirs

Examination of potential biomarkers of latent infection in the brain to determine if substances of abuse modulate the characteristics of latent HIV reservoirs, (e.g. comparing latent vs active virus upon exposure to substances of abuse)

Development of methods to image HIV integration into the genome of macrophage or glial cell types

Investigations into the role of DNA elements, transcriptional activity, and epigenetic mechanisms that suppress or enhance viral replication in the brain

Studies of neuronal and glial interactions that are affected by substances of abuse and impact HIV reservoirs

Correlation of levels of (or presence of specific) inflammatory mediators with viral reservoir size and/or activation or quiescence, which are distinct from the consequences of HIV pathology

Determine if brain latent virus reservoirs may differ from other sites of latent reservoirs (e.g. peripheral); and

Determine whether antiretroviral therapy interacts with substances of abuse to impact the integrity of brain HIV reservoirs

Transition to the R33 Phase

The progress report submitted at the end of R21 milestone will be reviewed by Program Administrator for transition to R33 phase. (see also, Section IV, 3. Reporting.)

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.

Meetings

The investigators funded under this FOA will be expected to attend annual meetings, at least once a year, in Bethesda, Maryland, to discuss research progress and highlight unexpected challenges. Funds to support the travel of principal investigators to attend these meetings should be included in the application budget

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:

Within the Specific Aims section, include headers titled "R21 Phase Specific Aims" and "R33 Phase Specific Aims". Under each header, state the specific objectives of the research and development effort, including the technical questions you will try to answer to determine the feasibility of the proposed approach. Since the R21 phase of this FOA is the exploratory/feasibility phase, hypothesis testing, per se, may not be the driving force in developing such an application, and therefore, may not be applicable in the R21 phase. The R21 phase could include descriptive, novel and untested approaches.

Research Strategy:

Applicants should provide a strong justification as to why the proposed model will provide a robust reflection of human HIV infection or provide a critical step along the way to understanding human HIV infection

The Research Strategy should consist of subsections for R21 and R33 phases.

The R21 Phase

The R21 phase of this FOA provides support to demonstrate the feasibility of the R33 project. Since exploratory applications are expected to be descriptive and hypothesis-generating in nature, pilot data that provide support for the proposed hypotheses and aims (i.e., Proof of Concept) are not required. However, applicants are encouraged to provide evidence that they have the capability to conduct the research by documenting the availability of needed resources, the training and experience of the investigator(s) and/or the conduct of related studies. The studies proposed in the R21 phase should be hypothesis-generating in nature, and not necessarily hypothesis-confirming.  The goal of such studies should be directed towards demonstrating feasibility rather than completion of a full study.

The R21 phase focuses on the development of technologies or biomarkers for detecting latent HIV virus in the brain, and the impact of substances of abuse on those reservoirs. The specific activities and milestones appropriate for the R21 phase will depend on the type of research and its stage of development.  In general, these activities and milestones could include, but are not limited to: 1) the objective measures of HIV latent virus in brain tissue and/or brains of living organisms; 2) feasibility for the technology or biomarker (i.e., the hypothesized mechanism of action) to be developed; 3) evidence that the technology or biomarker can be reliably and validly manipulated based on latent or activated HIV virus in the brain; 4) demonstration of adequate engagement of HIV latent and active reservoirs in brain tissue (in vitro and in vivo), including detection at varying viral reservoir sizes; and 5) feasibility data to indicate that the technology or biomarker evidencing presence and quantity of HIV reservoirs in the brain has the potential to be applied in humans.

Milestones: All applications must include a specific section labeled Milestones for each year of the study and these should be well-described, quantitative, and scientifically justified and not simply a restatement of the specific aims. Rather, the milestones should offer a timeline and a pathway for the progression of the proposed research from the R21 phase to R33 phase. Indicate when it is anticipated that essential milestones of the project will be completed. The proposed timeline should be clearly delineated and should appear as the last element of the Research Strategy section. For funded studies, these milestones will be used to judge the success of the research on an individual-project basis. It is expected that the milestones will be adjusted annually at the award anniversary dates to incorporate the project s scientific accomplishments and progress and to reflect any necessary adjustments to the plan stated in the application.

The R33 Phase

The R33 phase of this FOA provides funding contingent on successfully meeting the milestones in the R21 phase (see Section VI. Award Administration Information,1. Award Notices for further information). The R33 phase should test the link between the technology being developed or the biomarker being tested and characteristics of HIV latent reservoirs in the brain, such as size, activity, integrity, anatomical and cellular attributes, etc. Aims in the R33 phase may include, but are not limited to: 1) refinement and standardization; 2) preliminary testing of the association between a change in the target and potential clinical endpoints, or surrogate measures in animal models with clear proof-of-principal for human application.

Innovation: Include headers titled R21 Phase Innovation and R33 Phase Innovation, and address the Innovation for the R21 and R33 phases in the appropriate sub-section.

Approach: Include headers titled R21 Phase Approach and R33 Phase Approach, and address the Approach for the R21 and R33 phases in the appropriate sub-section.

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 NOT-OD-14-111, as applicable.

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 and responsiveness by components of participating organizations, 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 NOT-OD-13-030.

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.

For this particular announcement, note the following:

The R21/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R21/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.  Reviewers will assign a single impact score for the entire application, which includes both the R21 and R33 phases.

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the proposed project significantly improve our ability to detect latent HIV brain reservoirs? Will it enhance our understanding of the effects of substances of abuse on these reservoirs? Does the R21 portion of the application have the potential to advance to human studies?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the team have sufficient drug abuse and HIV expertise to be successful?

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? How well does the application utilize advances in our understanding of latent HIV brain reservoirs? How well developed is the substance abuse aspect of the application? Are the milestones set forth in the R21 application adequate for proof-of-principle? Are the appropriate controls in place? Does the approach address latent virus, active virus, or both? Are the R21 milestones appropriate and achievable during the R21 phase? Would achievement of the proposed R21 milestones be sufficient to qualify for transition to the R33 phase? Does the research plan of the R33 phase show a path to transitioning to human studies, either through brain banks or in vivo studies?

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.

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.

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 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.

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

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 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. 

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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. For funded applications, the PD/PI will submit a progress report to the Program Officer upon completion of the R21 milestones. Receipt of this progress report will trigger an administrative program review that will determine whether the R33 should be awarded. The release of R33 funds will be based on successful completion of negotiated scientific milestones, program priorities, and the availability of funds.

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 Commons Help Desk (Questions regarding 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: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

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

Vishnudutt Purohit, DVM, Ph.D.
National Institute on Drug Abuse (NIDA
Telephone: 301-594-5753
Email: [email protected]

Mark Swieter, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1389
Email: [email protected]

Debra Battle Dudley
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-6710
Email: [email protected]

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